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Background Various methods have been used to control body temperature in targeted temperature management (TTM), but few studies have compared specific subtypes of surface cooling systems. The aim of this study was to compare the efficiencies and neurological outcomes between hydrogels pad and water-circulating blanket cooling methods. Methods We conducted a multicentre, prospective, registry-based study of out-of-hospital cardiac arrest patients treated with TTM between 2015 and 2018. We compared the neurological outcomes, efficacies for cooling, and adverse events between patients who received TTM using a hydrogel pad and water-circulating blanket cooling. Patients were one-to-one matched using propensity scores to adjust for differences in the baseline characteristics of each cooling method. The primary outcome was a favourable neurological outcome at 6 months. Results We included 1,132 patients in the analysis, 870 of whom underwent hydrogel pad cooling, and the remaining 262 underwent water-circulating blanket cooling. In the unmatched cohort, a greater number of adverse events occurred in the water-circulating blanket group. The favourable neurologic outcome rates at 6 months were similar between the hydrogel pad group and the water circulating blanket group (30.2% vs. 29.8%, p = 0.939). In the propensity-matched cohort, which included 184 pairs, the rates of adverse events between the two groups were similar. The similarity of favourable neurologic outcome rates at 6 months between the two groups persisted (28.8% vs. 29.9%, p = 0.819). Conclusion Neurological outcomes and adverse events between the hydrogel pad cooling and water-circulating blanket cooling groups were similar.

We investigated whether controlled normothermia (CN) after the rewarming phase of targeted temperature management (TTM) is associated with preventing post-rewarming fever and outcomes 6 months after out-of-hospital cardiac arrest (OHCA).This was an analysis of a prospective registry comprising OHCA patients treated with TTM at 22 academic hospitals between October 2015 and December 2018. We calculated the incremental area under the curve (iAUC) for body temperature greater than or equal to 37.5 °C for each patient during the first 24 h after the end of rewarming. The relationships among CN and iAUC, 6-month survival and good neurological outcome were analysed. To minimize differences in the baseline characteristics of the patients, we used propensity score-matched analysis.In total, 1144 patients were enrolled. After propensity score matching, 646 patients (comprising 323 pairs) were obtained. In the unmatched cohort, post-rewarming CN was significantly associated with a lower iAUC (0.34 [1.38] vs. 1.19 [2.27]; p 0.001) but not 6-month survival (adjusted odds ratio (OR): 1.121; 95% confidence interval (CI): 0.836-1.504; p = 0.446) and good neurological outcome (adjusted OR: 1.030; 95% CI: 0.734-1.446; p = 0.863). The results were similar in the propensity score-matched cohort (0.38 [1.56] vs. 1.03 [2.21], p 0.001, OR: 1.347, 95% CI: 0.989-1.835, p = 0.059 and OR: 1.280, 95% CI 0.925-1.772, p = 0.137, respectively).Post-rewarming CN prevents high fever in the normothermia phase of TTM. However, our data suggest the lack of association between CN and the patient's 6-month survival and good neurological outcome.

Objective High-quality intensive care, including targeted temperature management (TTM) for patients with postcardiac arrest syndrome, is a key element for improving outcomes after out-of-hospital cardiac arrest (OHCA). We aimed to assess the status of postcardiac arrest syndrome care, including TTM and 6-month survival with neurologically favorable outcomes, after adult OHCA patients were treated with TTM, using data from the Korean Hypothermia Network prospective registry. Methods We used the Korean Hypothermia Network prospective registry, a web-based multicenter registry that includes data from 22 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TTM between October 2015 and December 2018 were included. The primary outcome was neurological outcome at 6 months. Results Of the 1,354 registered OHCA survivors treated with TTM, 550 (40.6%) survived 6 months, and 413 (30.5%) had good neurological outcomes. We identified 839 (62.0%) patients with preClinsumed cardiac etiology. A total of 937 (69.2%) collapses were witnessed, shockable rhythms were demonstrated in 482 (35.6%) patients, and 421 (31.1%) patients arrived at the emergency department with prehospital return of spontaneous circulation. The most common target temperature was 33°C, and the most common target duration was 24 hours. Conclusion The survival and good neurologic outcome rates of this prospective registry show great improvements compared with those of an earlier registry. While the optimal target temperature and duration are still unknown, the most common target temperature was 33°C, and the most common target duration was 24 hours.

Background During cardiac arrest (CA) and after cardiopulmonary resuscitation, activation of blood coagulation and inadequate endogenous fibrinolysis occur. The aim of this study was to describe the time course of coagulation abnormalities after out-of-hospital CA (OHCA) and to examine the association with clinical outcomes in patients undergoing targeted temperature management (TTM) after OHCA. Methods This prospective, multicenter, observational cohort study was performed in eight emergency departments in Korea between September 2018 and September 2019. Laboratory findings from hospital admission and 24 hours after return of spontaneous circulation (ROSC) were analyzed. The primary outcome was cerebral performance category (CPC) at discharge, and the secondary outcome was in-hospital mortality. Results A total of 170 patients were included in this study. The lactic acid, prothrombin time (PT), activated partial thrombin time (aPTT), international normalized ratio (INR), and D-dimer levels were higher in patients with poor neurological outcomes at admission and 24 h after ROSC. The lactic acid and D-dimer levels decreased over time, while fibrinogen increased over time. PT, aPTT, and INR did not change over time. The PT at admission and D-dimer levels 24 h after ROSC were associated with neurological outcomes at hospital discharge. Coagulation-related factors were moderately correlated with the duration of time from collapse to ROSC. Conclusion The time-dependent changes in coagulation-related factors are diverse. Among coagulation-related factors, PT at admission and D-dimer levels 24 h after ROSC were associated with poor neurological outcomes at hospital discharge in patients treated with TTM.

Background: In patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (pPCI), longer door-to-balloon (DTB) time is known to be associated with an unfavorable outcome. A percentage of patients with acute coronary occlusion present with atypical electrocardiographic (ECG) findings, known as STEMI-equivalents. We investigated whether DTB time for STEMI-equivalent patients was delayed. Methods: This is a retrospective study including patients arriving at an emergency department with the acute coronary syndrome in whom emergent pPCI was performed. ECGs were classified into STEMI and STEMI-equivalent groups. We compared DTB time, with its components, between the groups. We also investigated whether STEMI-equivalent ECG was an independent predictor of DTB time delayed for more than 90 min. Results: A total of 180 patients were included in the present study, and 23 patients (12.8%) presented with STEMI-equivalent ECGs. DTB time was significantly delayed in patients with STEMI-equivalent ECGs (89 (80–122) vs. 81 (70–88) min, p = 0.001). Multivariable logistic regression analysis showed that STEMI-equivalent ECG was an independent predictor of delayed DTB time (odds ratio: 4.692; 95% confidence interval: 1.632–13.490, p = 0.004). Conclusions: DTB time was significantly delayed in patients presenting with STEMI-equivalent ECGs. Prompt recognition of STEMI-equivalent ECGs by emergency physicians and interventional cardiologists might reduce DTB time and lead to a better clinical outcome.

Purpose We analysed the prognostic value of somatosensory, brainstem auditory and visual evoked potentials (SSEPs, BAEPs and VEPs, respectively) for outcome prediction in cardiac arrest patients with targeted temperature management (TTM) and assessed whether BAEP and VEP measurements conferred added value to SSEP measurements. Methods Cases with SSEPs and VEPs or BAEPs were reviewed in a TTM registry. We focused on whether the following responses were clearly discernible: N20 for SSEPs, V for BAEPs, and P100 for VEPs. Each type of evoked potential was classified as absent, present or indeterminable. Neurological outcomes after 6 months were dichotomized as good (Cerebral Performance Category [CPC] 1–2) or poor (CPC 3–5). Results From 185 patients, 185 SSEPs, 172 BAEPs and 178 VEPs were included. None of the patients with a good outcome had absent SSEP, BAEP or VEP responses. Absent SSEP, BAEP and VEP responses yielded sensitivities of 42.3% (95% confidence interval [CI], 33.7–51.3%), 9.4% (95% CI, 4.6–16.7%) and 54.4% (95% CI, 46.0–62.5%) for poor outcomes, respectively. For the overall cohort, the addition of VEP measurements improved the sensitivities of single SSEP measurements (65.8% [95% CI, 57.7–73.3%] versus 36.2% [95% CI, 28.6–44.4%] and multimodal prognostication using SSEPs, brainstem reflex and brain computed tomography (75.7% [95% CI, 68.0–82.3%] versus 60.5% [95% CI, 52.3–68.4%]). Conclusions The prognostic value of VEPs was comparable to that of SSEPs, but the use of BAEPs was limited due to their low sensitivity. Additional VEP measurements can reduce prognostic uncertainty.

Objectives: Anaphylaxis refractory to epinephrine treatment is a potentially fatal condition requiring additional medications. Neutrophil-to lymphocyte ratio (NLR) is commonly used to predict severity in allergic diseases. The aim of this study was to determine the association between NLR and refractory anaphylaxis. Methods: This was a retrospective, observational study of 126 adult anaphylaxis patients arriving at the emergency department between January 2015 and December 2019. Patients were placed into refractory anaphylaxis, if they required more than two 0.3 mg injections of intramuscular epinephrine for symptom resolution, and non-refractory anaphylaxis groups. NLRs were determined at the time of arrival at the hospital and were compared between groups. Results: Thirty-two (25.4%) patients were categorized as refractory anaphylaxis cases. NLR was significantly lower in the refractory anaphylaxis than in the non-refractory anaphylaxis group (P < 0.001). In the multivariate logistic regression analysis model, NLR was inversely associated with the occurrence of refractory anaphylaxis (adjusted odds ratio 0.33, 95% confidence interval 0.13-0.81, P = 0.016). The area under the receiver operating characteristic curve of NLR for prediction of refractory anaphylaxis was 0.717 (P < 0.001). The optimal cut-off value of NLR was < 0.68 using the Youden index, with 50.0% sensitivity and 80.9% specificity. Conclusions: NLR was independently and inversely associated with the occurrence of refractory anaphylaxis among anaphylactic patients. Therefore, NLR has the potential to be used as an easy and inexpensive test to predict refractory anaphylaxis in patients.

It has been reported that valproic acid (VPA) combined with therapeutic hypothermia can improve survival and neurologic outcomes in a rat asphyxial cardiac arrest model. However, neuroprotective mechanisms of such combined treatment of valproic acid with hypothermia remains unclear. We hypothesized that epigenetic regulation of HSP70 by histone acetylation could increase HSP70-mediated neuroprotection suppressed under hypothermia. Male Sprague-Dawley rats that achieved return of spontaneous circulation (ROSC) from asphyxial cardiac arrest were randomized to four groups: normothermia (37°C ± 1°C), hypothermia (33°C ± 1°C), normothermia + VPA (300 mg/kg IV initiated 5 minutes post-ROSC and infused over 20 min), and hypothermia + VPA. Three hours after ROSC, acetyl-histone H3 was highly expressed in VPA-administered groups (normothermia + VPA, hypothermia + VPA). Four hours after ROSC, HSP70 mRNA expression levels were significantly higher in normothermic groups (normothermia, normothermia + VPA) than in hypothermic groups (hypothermia, hypothermia + VPA). The hypothermia + VPA group showed significantly higher HSP70 mRNA expression than the hypothermia group. Similarly, at five hours after ROSC, HSP70 protein levels were significantly higher in normothermic groups than in hypothermic groups. HSP70 levels were significantly higher in the hypothermia + VPA group than in the hypothermia group. Only the hypothermia + VPA group showed significantly attenuated cleaved caspase-9 levels than the normothermia group. Hypothermia can attenuate the expression of HSP70 at transcriptional level. However, VPA administration can induce hyperacetylation of histone H3, leading to epigenetic transcriptional activation of HSP70 even in a hypothermic status. Combining VPA treatment with hypothermia may compensate for reduced activation of HSP70-mediated anti-apoptotic pathway.

Background While multivessel coronary artery disease (CAD) is frequently observed in out-of-hospital cardiac arrest (OHCA) survivors, little is known about the impact of revascularization strategy on outcomes. We aimed to evaluate the prevalence of left main or triple vessel CAD in comatose survivors of OHCA and assess their outcome based on the revascularization strategy. Methods This multicenter retrospective cohort study was conducted at 9 Korean tertiary care hospitals. Adult comatose OHCA survivors with left main or triple vessel CAD documented by immediate (≤ 2 hours) coronary angiography after return of spontaneous circulation between 2011 and 2019 were included. The primary outcome was neurologically intact survival at 1-month defined as survival with a Cerebral Performance Category score of 1–2. Results Among 727 OHCA patients with immediate coronary angiography, 150 (25.3%) with left main or triple vessel CAD were identified and categorized into complete (N = 32), incomplete (N = 78), and no immediate (N = 40) revascularization groups. The rate of neurologically intact survival at 1 month was significantly different among the groups (53.1%, 32.1%, and 22.5% for complete, incomplete, and no immediate revascularization groups, respectively; P = 0.021). After adjustment using the inverse probability of treatment weighting, complete revascularization was independently associated with neurologically intact survival at 1 month (odds ratio, 2.635; 95% confidence interval, 1.128–6.155; P = 0.012). Conclusions Left main or triple vessel CAD is not uncommon in comatose OHCA patients. The rate of neurologically intact survival at 1 month was 34.0%, and it was significantly greater in patients with complete revascularization than in patients with incomplete or no immediate revascularization. Further clinical trials will be needed to confirm the best revascularization strategy to improve outcomes in such critically ill patients.

Objectives The aim of this study was to evaluate the prognostic performance of the peak amplitude of P25/30 cortical somatosensory evoked potentials in predicting nonawakening in targeted temperature management-treated cardiac arrest patients. Design Prospective analysis. Setting Four academic tertiary care hospitals. Patients Eighty-seven cardiac arrest survivors after targeted temperature management. Interventions Analysis of the amplitude of P25/30. Measurements and main results In all participants, somatosensory evoked potentials were recorded after rewarming, and bilaterally absent pupillary and corneal reflexes were evaluated at 72 hours after the return of spontaneous circulation. We analyzed the amplitudes of the N20 and P25/30 peaks and the N20-P25/30 complex in cortical somatosensory evoked potentials. Upon hospital discharge, 87 patients were dichotomized into the awakening and nonawakening groups. The lowest amplitudes of N20, P25/30, and N20-P25/30 in the awakening patients were 0.17, 0.45, and 0.73 μV, respectively, and these thresholds showed a sensitivity of 70.5% (95% CI, 54.8-83.2%), 86.4% (95% CI, 72.7-94.8%), and 75.0% (95% CI, 59.7-86.8%), respectively, for nonawakening. The area under the curve of the P25/30 amplitude was significantly higher than that of the N20 amplitude (0.955 [95% CI, 0.912-0.998] vs 0.894 [95% CI, 0.819-0.969]; p = 0.036) and was comparable with that of the N20-P25/30 amplitude (0.931 [95% CI, 0.873-0.989]). Additionally, adding resuscitation variables or an absent brainstem reflex to the P25/30 amplitude showed a trend toward improving prognostic performance compared with the use of other somatosensory evoked potential amplitudes (area under the curve, 0.958; 95% CI, 0.917-0.999 and area under the curve, 0.974; 95% CI, 0.914-0.996, respectively). Conclusions Our results provide evidence that the absence of the P25/30 peak and a reduction in the P25/30 amplitude may be considered prognostic indicators in these patients.

Background Paricalcitol is known to attenuate ischemic-reperfusion injury of various organs. However, it is not known whether paricalcitol prevents neuronal injury after global cerebral ischemia. The purpose of this study is to investigate the neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia. Methods This is a prospective, randomized experimental study. Male Sprague-Dawley rats that survived 10 min of four-vessel occlusion were randomly assigned to two treatment groups: one group was treated with paricalcitol 1 μg/kg IP, and the other was given an equivalent volume of normal saline IP. Drugs were administered at 5 min, 1 day, 2 days, and 3 days after ischemia. Neurologic function was assessed at 2 h, 1 day, 2 days, 3 days, and 4 days after ischemia. We tested motor function 3 days after ischemia using the rotarod test. Also, we tested memory function 4 days after ischemia using the passive avoidance test. We assessed neuronal degeneration in the hippocampus of surviving rats 4 days after ischemia. Results Eight rats were allocated to each group. No significant differences were found between the groups in terms of survival rate, motor coordination, or memory function. The neurological function score 2-h post-ischemia was significantly higher in the paricalcitol group (p = 0.04). Neuronal degeneration was significantly less in the paricalcitol group compared with the control group (p = 0.01). Conclusions Paricalcitol significantly attenuated neuronal injury in the hippocampus. Although motor coordination, memory function, and survival rate were not significantly improved by paricalcitol treatment in this study, paricalcitol remains a potential neuroprotective drug after global cerebral ischemia.

Objectives Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by various tissues in pathologic states. Previous studies reported that post-cardiac arrest serum NGAL levels correlate with short-term neurologic outcomes and survival. The aim of this study was to examine the associations between NGAL levels post-cardiac arrest and long-term outcomes and survival. Methods This prospective observational study and retrospective review included adult out-of-hospital cardiac arrest survivors who were treated by hypothermia-targeted temperature management. Serum NGAL was assessed at 0, 24, 48, and 72 h after return of spontaneous circulation. The primary outcome was poor outcome at six months after cardiac arrest, defined as cerebral performance category score of 3–5. The secondary outcome was six-month mortality. Results In total, 76 patients were analyzed. The patients with poor outcomes showed significantly higher NGAL levels at 24, 48 and 72 h after cardiac arrest than the patients with good outcomes. Long-term survival rates were significantly lower in the high-NGAL group than in the low-NGAL group at each time point. Subgroup analysis of patients who survived 72 h showed that only serum NGAL 72 h after cardiac arrest had prognostic value for long-term outcomes (area under the receiver operating characteristic curve = 0.72; p = 0.02). Conclusions Post-cardiac arrest serum NGAL is associated with long-term outcomes and survival; particularly, three days post-cardiac arrest is the optimal time point for predicting long-term outcomes. However, the predictive power of NGAL is unsatisfactory, and it should be regarded as an additional prognostic modality.

In attempted suicide, laryngotracheal rupture caused by hanging leads to rapid death at the scene or before arrival at hospital. The case presented here describes a patient with complete tracheal rupture from an attempted suicidal hanging who was successfully resuscitated. Pre-hospital providers transferred the patient to hospital without being aware of the possibility of airway damage. Cardiac arrest occurred shortly after arrival at hospital. During the cardiopulmonary resuscitation, endotracheal intubation was performed, and fortunately, the tracheal tube was located just below the ruptured trachea and thus enabled ventilation. For patients suspected of having airway damage at the pre-hospital stage, awareness of the patient’s condition and adequate airway management are important. The management of laryngotracheal rupture which suggests that for patients not adequately ventilated, immediate treatment with flexible fiberoptic intubation or tracheostomy is needed to secure the airway. Equipment and personnel at the receiving hospital need to be prepared for immediate treatment.

Background The reliability of somatosensory evoked potential (SSEP) to predict a poor outcome of cardiac arrest patients after targeted temperature management (TTM) has been questioned due to self-fulfilling prophecy. Methods This was a multicentre, prospective, registry-based study. Data were collected from the Korean Hypothermia Network (KORHN)-pro registry between November 2015 and December 2018. We excluded cases with possible bias (inappropriate SSEP recordings and patients who decided on the withdrawal of life-sustaining therapy [WLST]) and calculated the sensitivities and false positive rates (FPRs) for an absent N20 and an absent brainstem reflex. A poor outcome was defined as a cerebral performance category score of 3–5 after 6 months. Results A total of 262 patients were analysed: 83 in the good outcome group and 179 in the poor outcome group. A bilaterally absent N20 was found in 127 patients and predicted a poor outcome with a sensitivity of 71.0% (95% confidence interval [CI], 63.7–77.5) and an FPR of 0.0% (95% CI, 0.0–4.3). Among the patients with absent brainstem reflexes (n = 103), 3 had a good outcome, with an FPR of 4.3% (95% CI, 0.9–12.2). The absence of one or both N20 and brainstem reflex had a sensitivity of 84.2% (95% CI, 77.4–89.6) and an FPR of 4.3% (95% CI, 0.9–12.2). Conclusions Our results provide further evidence that SSEP exactly predicts poor neurological outcome in these patients and suggest that caution be taken when the brainstem reflex is used as a single test to make decisions regarding WLST.

Background We hypothesized that the absence of P25 and the N20–P25 amplitude in somatosensory evoked potentials (SSEPs) have higher sensitivity than the absence of N20 for poor neurological outcomes, and we evaluated the ability of SSEPs to predict long-term outcomes using pattern and amplitude analyses. Methods Using prospectively collected therapeutic hypothermia registry data, we evaluated whether cortical SSEPs contained a negative or positive short-latency wave (N20 or P25). The N20–P25 amplitude was defined as the largest difference in amplitude between the N20 and P25 peaks. A good or poor outcome was defined as a Glasgow-Pittsburgh Cerebral Performance Category (CPC) score of 1–2 or 3–5, respectively, 6 months after cardiac arrest. Results A total of 192 SSEP recordings were included. In all patients with a good outcome (n = 51), both N20 and P25 were present. Compared to the absence of N20, the absence of N20–P25 component improved the sensitivity for predicting a poor outcome from 30.5% (95% confidence interval [CI], 23.0–38.8%) to 71.6% (95% CI, 63.4–78.9%), while maintaining a specificity of 100% (93.0–100.0%). Using an amplitude

Introduction: Several studies have shown that the alpha-delta ratio (ADR) is associated with ischemic brain injury. Recently, an animal study has revealed that the ADR reaches the maximum point at 11 hours after ROSC, followed by downward curve (ADR peak) in the continuous EEG recordings of the rats with good outcome after cardiac arrest. We examined the existence of the early ADR peak after cardiac arrest in human. Methods: This is a prospective, observational study. Forty patients who survived out-of-hospital cardiac arrest underwent 33°C-targeted temperature management. We induced 33°C within 5 hours after ROSC and maintained for 24 hours, followed by 12 hours of rewarming period. All patients received sedative and paralytic agents until the restoration of normothermia. We started continuous EEG monitoring within 20 hours after ROSC until 72 hours after ROSC or mental recovery. We calculated alpha (8 - 13 Hz) and delta (0.5 - 4 Hz) frequency bands and computed ADR in the bifrontal channel (F3 - F4), bicentral channel (C3 - C4) and biparietal channel (P3 - P4). We did not remove artifact nor seizure events. Therefore, the whole continuous recordings were analyzed. Good neurologic outcome was defined as cerebral performance category 1 and 2 one month after ROSC. Results: Twenty-five patients showed poor outcome, while 15 patients showed good outcome. The figure is showing mean ADR ± SD change over time. The ADR reaches its highest amplitude 10 hours after ROSC and gradually decreases in the patients with good outcome regardless of the recording channel. However, the 10-hour ADR was not significantly different between the groups due to the large variances. Conclusions: Similar to the rats, the ADR peak appears early in the human patients with good outcome. However, due to the highly variable trend, application of ADR peak as a prognostic marker is limited. Regardless, the ADR implicates the crucial window of brain recovery time and remains an important subject requiring further study.

OBJECTIVES The absence of N20 somatosensory evoked potential after cardiac arrest is related to poor outcome. However, discrimination between the low-amplitude and the absence of N20 is challenging. P25 and P30 are short-latency positive peaks with latencies between 25 and 30 ms following N20 (P25/30). P25/30 is evident even with an ambiguous N20 in patients with good outcome. Therefore, we evaluated the predictive value of P25/30 after cardiac arrest. DESIGN A retrospective observational study. SETTING University-affiliated hospital. SUBJECTS Comatose survivors after out-of-hospital cardiac arrest treated by hypothermic targeted temperature management. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS The specificity and the positive predictive value of P25/30 and N20 in predicting poor outcome were the same, showing a rate of 100%. The sensitivity of P25/30 in predicting poor outcome (90.12% [95% CI, 81.5-95.6%]) was higher than that of N20 (70.37% [95% CI, 59.2-80%]). Also, the negative predictive value of P25/30 in predicting poor outcome (81.4% [95% CI, 69.4-89.4%]) was higher than that of N20 (59.3% [95% CI, 51-67.1%]). The P25/30-based adjusted model showed a larger area under the curve (0.98 [95% CI, 0.95-1]) compared with the N20-based adjusted model (0.95 [95% CI, 0.91-0.98]) (p = 0.02). CONCLUSIONS The absence of P25/30 is related to poor outcome with a higher sensitivity, negative predictive value than the absence of N20.

OBJECTIVES High-dose valproic acid in combination with hypothermic-targeted temperature management has been reported to synergistically improve neurologic outcomes after cardiac arrest. This study investigated the potential synergistic mechanisms. DESIGN Prospective, randomized, experimental study. SETTING University research institution. SUBJECTS Male Long Evans rats. INTERVENTION Rats resuscitated from asphyxial cardiac arrest were randomized to one of the three groups: normothermic-targeted temperature management (37°C ± 1°C), hypothermic-targeted temperature management (33° ± 1° × 24 hr + placebo infusion), hypothermic-targeted temperature management plus high-dose valproic acid (300 mg/kg IV × 1 initiated 5 min post return of spontaneous circulation and infused over 20 min) (hypothermic-targeted temperature management + valproic acid). MEASUREMENTS AND MAIN RESULTS Seventy-two-hour survival was significantly greater with hypothermic-targeted temperature management + valproic acid, compared to hypothermic-targeted temperature management and normothermic-targeted temperature management (p < 0.05). Survival with good neurologic function, neurodegeneration, expression of HSP70, phosphorylation of Akt and Erk1/2 were not significantly different between hypothermic-targeted temperature management and hypothermic-targeted temperature management + valproic acid. The prevalence of seizures during the first 72-hour postcardiac arrest was significantly lower with hypothermic-targeted temperature management + valproic acid compared to hypothermic-targeted temperature management and normothermic-targeted temperature management (p = 0.01). CONCLUSIONS High-dose valproic acid combined with hypothermic-targeted temperature management prevents postcardiac arrest seizures and improves survival. It remains to be determined if the mechanism of seizure prevention is through the antiepileptic effect of valproic acid or direct neuroprotection. Overall, the combination of high-dose valproic acid and hypothermic-targeted temperature management remains a promising strategy to improve cardiac arrest outcomes.

Purposes In cardiac arrest patients treated with targeted temperature management (TTM), it is not certain if somatosensory evoked potentials (SEPs) and visual evoked potentials (VEPs) can predict neurological outcomes during TTM. The aim of this study was to investigate the prognostic value of SEPs and VEPs during TTM and after rewarming. Methods This retrospective cohort study included comatose patients resuscitated from cardiac arrest and treated with TTM between March 2007 and July 2015. SEPs and VEPs were recorded during TTM and after rewarming in these patients. Neurological outcome was assessed at discharge by the Cerebral Performance Category (CPC) Scale. Results In total, 115 patients were included. A total of 175 SEPs and 150 VEPs were performed. Five SEPs during treated with TTM and nine SEPs after rewarming were excluded from outcome prediction by SEPs due to an indeterminable N20 response because of technical error. Using 80 SEPs and 85 VEPs during treated with TTM, absent SEPs yielded a sensitivity of 58% and a specificity of 100% for poor outcome (CPC 3–5), and absent VEPs predicted poor neurological outcome with a sensitivity of 44% and a specificity of 96%. The AUC of combination of SEPs and VEPs was superior to either test alone (0.788 for absent SEPs and 0.713 for absent VEPs compared with 0.838 for the combination). After rewarming, absent SEPs and absent VEPs predicted poor neurological outcome with a specificity of 100%. When SEPs and VEPs were combined, VEPs slightly increased the prognostic accuracy of SEPs alone. Although one patient with absent VEP during treated with TTM had a good neurological outcome, none of the patients with good neurological outcome had an absent VEP after rewarming. Conclusion Absent SEPs could predict poor neurological outcome during TTM as well as after rewarming. Absent VEPs may predict poor neurological outcome in both periods and VEPs may provide additional prognostic value in outcome prediction.

There is little consensus regarding many post-cardiac arrest care parameters. Variability in such practices could confound the results and generalizability of post-arrest care research. We sought to characterize the variability in post-cardiac arrest care practice in Korea and the United States. A 54-question survey was sent to investigators participating in one of two research groups in South Korea (Korean Hypothermia Network [KORHN]) and the United States (National Post-Arrest Research Consortium [NPARC]). Single investigators from each site were surveyed (N = 40). Participants answered questions based on local institutional protocols and practice. We calculated descriptive statistics for all variables. Forty surveys were completed during the study period with 30 having greater than 50% of questions completed (75% response rate; 24 KORHN and 6 NPARC). Most centers target either 33°C (N = 16) or vary the target based on patient characteristics (N = 13). Both bolus and continuous infusion dosing of sedation are employed. No single indication was unanimous for cardiac catheterization. Only six investigators reported having an institutional protocol for withdrawal of life-sustaining therapy (WLST). US patients with poor neurological prognosis tended to have WLST with subsequent expiration (N = 5), whereas Korean patients are transferred to a secondary care facility (N = 19). Both electroencephalography modality and duration vary between institutions. Serum biomarkers are commonly employed by Korean, but not US centers. We found significant variability in post-cardiac arrest care practices among US and Korean medical centers. These practice variations must be taken into account in future studies of post-arrest care.

Objective Therapeutic hypothermia is now regarded as the only effective treatment of global ischemic injury after cardiac arrest. Numerous studies of the neuroprotective effects of 17 β -estradiol have yielded conflicting results depending on administration route and dose. Herein, we investigated the neuroprotective effect of postischemic 17 β -estradiol administration combined with therapeutic hypothermia. Methods Twenty-one rats were randomly divided into 4 groups: control (group I), therapeutic hypothermia (group II), 17 β -estradiol treatment (group III), and therapeutic hypothermia combined with 17 β -estradiol treatment (group IV). One rat was assigned to a sham operation group. With the exception of the sham-operated rat, all animals underwent transient global cerebral ischemia for 20 minutes by the 4-vessel occlusion method. Hypothermia was maintained at 33°C for 2 hours in groups II and IV, and 17 β -estradiol (10 μ g/kg) was intraperitoneally administered to rats in groups III and IV. Neurologic deficit scores and hippocampal cornu ammonis 1 neuronal injury were assessed 72 hours postischemia. Results The neurologic deficit score was not significantly different among the groups. The percentage of normal neurons in the hippocampal cornu ammonis 1 was 7.32% ± 0.88% in group I, 53.65% ± 2.52% in group II, 51.6% ± 3.44% in group III, and 79.79% ± 1.6% in group IV. The neuroprotective effect in the combined treatment group was markedly greater than in the single treatment groups, which suggests that hypothermia and 17 β -estradiol work synergistically to exert neuroprotection. Conclusion Postischemic administration of low-dose 17 β -estradiol appears to be neuroprotective after transient global ischemia, and its effect is potentiated by therapeutic hypothermia.

Situs inversus totalis is a rare inherent disease in which the thoracic and abdominal organs are transposed. Symptoms of appendicitis in situs inversus (SI) may appear in the left lower quadrant, and the diagnosis of appendicitis is very difficult. We report a case of left-sided appendicitis diagnosed preoperatively after dextrocardia that was detected by chest X-ray, although the chief complaint of the patient was left lower-quadrant pain. The patient underwent an emergent laparoscopic appendectomy under the diagnosis of appendicitis after abdominal computed tomography (CT). In patients with left lower quadrant pain, if the chest X-ray shows dextrocardia, one should suspect left-sided appendicitis. A strong suspicion of appendicitis and an emergency laparoscopic operation after confirmation of the diagnosis by imaging modalities including abdominal CT or sonography can reduce the likelihood of misdiagnosis and complications including perforation and abscess. Laparoscopic appendectomy in SI was technically more challenging because of the mirror nature of the anatomy.

Purpose This study evaluated the prognostic performance of the gray to white matter ratio (GWR) on brain computed tomography (CT) in out-of-hospital cardiac arrest (OHCA) survivors with a noncardiac etiology and compared the prognostic performance of GWR between hypoxic and nonhypoxic etiologies. Methods Using a multicenter retrospective registry of adult OHCA patients treated with targeted temperature management, we identified those with a noncardiac etiology who underwent brain CT within 24 hours after restoration of spontaneous circulation. Attenuation of the gray matter and white matter (at the level of the basal ganglia, centrum semiovale, and high convexity) were measured and GWRs were calculated. The primary outcome was neurologic outcome. Results Of 164 patients, 145 (88.4%) were discharged with a poor neurologic outcome. Lower GWR was associated with a poor neurologic outcome. The sensitivities of this marker were markedly low (9.7%-43.5%) at cutoff values, with 100% sensitivity. The cutoff values of the GWR for hypoxic arrest showed higher sensitivities than those for nonhypoxic arrest. The area under the curve (AUC) values of the GWR for the caudate nucleus/posterior limb of the internal capsule, putamen/corpus callosum, and basal ganglia were significant in the hypoxic group, whereas the AUC of the putamen/corpus callosum was the only significant GWR in the nonhypoxic group. Conclusion A low GWR is associated with poor neurologic outcome in noncardiac etiology OHCA patients treated with targeted temperature management. Gray to white matter ratio can help to predict the neurologic outcome in a cardiac arrest with hypoxic etiology rather than a nonhypoxic etiology.

Introduction Various methods and devices have been described for cooling after cardiac arrest, but the ideal cooling method remains unclear. The aim of this study was to compare the neurological outcomes, efficacies and adverse events of surface and endovascular cooling techniques in cardiac arrest patients. Methods We performed a multicenter, retrospective, registry-based study of adult cardiac arrest patients treated with therapeutic hypothermia presenting to 24 hospitals across South Korea from 2007 to 2012. We included patients who received therapeutic hypothermia using overall surface or endovascular cooling devices and compared the neurological outcomes, efficacies and adverse events of both cooling techniques. To adjust for differences in the baseline characteristics of each cooling method, we performed one-to-one matching by the propensity score. Results In total, 803 patients were included in the analysis. Of these patients, 559 underwent surface cooling, and the remaining 244 patients underwent endovascular cooling. In the unmatched cohort, a greater number of adverse events occurred in the surface cooling group. Surface cooling was significantly associated with a poor neurological outcome (cerebral performance category 3–5) at hospital discharge (p = 0.01). After propensity score matching, surface cooling was not associated with poor neurological outcome and hospital mortality [odds ratio (OR): 1.26, 95% confidence interval (CI): 0.81-1.96, p = 0.31 and OR: 0.85, 95% CI: 0.55-1.30, p = 0.44, respectively]. Although surface cooling was associated with an increased incidence of adverse events (such as overcooling, rebound hyperthermia, rewarming related hypoglycemia and hypotension) compared with endovascular cooling, these complications were not associated with surface cooling using hydrogel pads. Conclusions In the overall matched cohort, no significant difference in neurological outcomes and hospital morality was observed between the surface and endovascular cooling methods.

IntroductionThe aim of this study was to investigate the association of adverse events (AEs) during targeted temperature management (TTM) and other AEs and concomitant treatments during the advanced critical care period with poor neurological outcome at hospital discharge in adult out-of-hospital cardiac arrest (OHCA) patients.MethodsThis was a retrospective study using Korean Hypothermia Network registry data of adult OHCA patients treated with TTM in 24 teaching hospitals throughout South Korea from 2007 to 2012. Demographic characteristics, resuscitation and post-resuscitation variables, AEs, and concomitant treatments during TTM and the advanced critical care were collected. The primary outcome was poor neurological outcome, defined as a cerebral performance category (CPC) score of 3–5 at hospital discharge. The AEs and concomitant treatments were individually entered into the best multivariable predictive model of poor neurological outcome to evaluate the associations between each variable and outcome.ResultsA total of 930 patients, including 704 for whom a complete dataset of AEs and covariates was available for multivariable modeling, were included in the analysis; 476 of these patients exhibited poor neurological outcome [CPC 3 = 50 (7.1 %), CPC 4 = 214 (30.4 %), and CPC 5 = 212 (30.1 %)]. Common AEs included hyperglycemia (45.6 %), hypokalemia (31.3 %), arrhythmia (21.3 %) and hypotension (29 %) during cooling, and hypotension (21.6 %) during rewarming. Bleeding (5 %) during TTM was a rare AE. Common AEs during the advanced critical care included pneumonia (39.6 %), myoclonus (21.9 %), seizures (21.7 %) and hypoglycemia within 72 hours (23 %). After adjusting for independent predictors of outcome, cooling- and rewarming-related AEs were not significantly associated with poor neurological outcome. However, sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care were associated with poor neurological outcome [adjusted odds ratios (95 % confidence intervals) of 3.12 (1.40–6.97), 3.72 (1.93–7.16), 4.02 (2.04–7.91), 2.03 (1.09–3.78), and 1.69 (1.03–2.77), respectively]. Alternatively, neuromuscular blocker use was inversely associated with poor neurological outcome (0.48 [0.28–0.84]).ConclusionsCooling- and rewarming-related AEs were not associated with poor neurological outcome at hospital discharge. Sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care period were associated with poor neurological outcome at hospital discharge in our study.

Objectives The Surviving Sepsis Campaign has recommended that antibiotic therapy should be started within the first hour of recognizing severe sepsis. Procalcitonin has recently been proposed as a biomarker of bacterial infection, although the quantitative procalcitonin assay is often time consuming, and it is not always available in many emergency departments (EDs). Our aim is to evaluate usefulness of the semiquantitative procalcitonin fast kit as a guideline for starting antibiotic administration for patients with severe sepsis or septic shock that requires prompt antibiotic therapy in the ED. Methods We include those patients who were admitted to the ED and who were suspected of having infection. The procalcitonin concentration was determined by semiquantitative PCT-Q strips, and the points of the severity scoring system were calculated. The receiver operating characteristic curve was used to assess the diagnostic value of the PCT-Q strips to predict severe sepsis or septic shock. Results Of the 80 recruited patients, 33 patients were categorized as having severe sepsis or septic shock according to the definition. At a procalcitonin cutoff level of 2 ng/mL or greater, the sensitivity of the PCT-Q for detecting severe sepsis or septic shock was 93.94% and the specificity was 87.23. The receiver operating characteristic curve for PCT-Q to predict severe sepsis or septic shock had an area under the curve of 0.916. Conclusion PCT-Q is probably a fast, useful method for detecting severe sepsis in the ED, and it can be used as a guideline for antibiotic treatment.

Hypothermia increases clotting time, which is known as hypothermic coagulopathy. However, prothrombin time and activated partial thromboplastin time prolongation associated with therapeutic hypothermia is usually mild and thus, hypothermic coagulopathy is not considered to cause clinically significant bleeding. On the other hand, PT and aPTT do not seem to reflect the severity of hypothermic coagulopathy. Serious bleeding complications of therapeutic hypothermia has not been reported previously. Herein, we introduce a case of spontaneous brain stem hemorrhage as a complication of therapeutic hypothermia-induced coagulopathy.