Early Left Ventricular Unloading or Conventional Approach After Venoarterial Extracorporeal Membrane Oxygenation: The EARLY-UNLOAD Randomized Clinical Trial.

BACKGROUND: Although venoarterial extracorporeal membrane oxygenation (VA-ECMO) is beneficial for the treatment of profound cardiogenic shock, peripheral VA-ECMO cannulation can increase left ventricular afterload, thus compromising myocardial recovery. We investigated whether early routine left ventricular unloading can reduce 30-day mortality compared with the conventional approach in patients with cardiogenic shock undergoing VA-ECMO. METHODS: This randomized clinical trial involved 116 patients with cardiogenic shock undergoing VA-ECMO from March 2021 to September 2022 at Chonnam National University Hospital, Gwangju, South Korea. The patients were randomly assigned to undergo either early routine left ventricular unloading with transseptal left atrial cannulation within 12 hours after randomization (n=58) or the conventional approach, which permitted rescue transseptal left atrial cannulation in case of an increased left ventricular afterload (n=58). The primary outcome was all-cause mortality within 30 days. RESULTS: All 116 randomized patients (mean age, 67.6±13.5 years; 34 [29.3%] women) completed the trial. At 30 days, all-cause death had occurred in 27 (46.6%) patients in the early group and 26 (44.8%) patients in the conventional group (hazard ratio, 1.02 [95% CI, 0.59-1.74]; P=0.942). Crossover to rescue transseptal left atrial cannulation occurred in 29 patients (50%) in the conventional group according to a clear indication. Time to rescue transseptal cannulation in the conventional group was a median of 21.8 (interquartile range, 12.4-52.2) hours after randomization. There were no significant differences in other secondary outcomes between the 2 groups except for a shorter time to disappearance of pulmonary congestion in the early group (median, 3 [interquartile range, 2-6] versus 5 [interquartile range, 3-7] days; P=0.027). CONCLUSIONS: Among patients with cardiogenic shock undergoing VA-ECMO, early routine left ventricular unloading with transseptal left atrial cannulation did not reduce 30-day mortality compared with the conventional strategy, which permitted rescue transseptal left atrial cannulation. These findings should be cautiously interpreted until the results of multicenter trials using other unloading modalities become available. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04775472.

Feasibility of Magnetic Resonance-Based Conductivity Imaging as a Tool to Estimate the Severity of Hypoxic-Ischemic Brain Injury in the First Hours After Cardiac Arrest.

BACKGROUND: Early identification of the severity of hypoxic-ischemic brain injury (HIBI) after cardiac arrest can be used to help plan appropriate subsequent therapy. We evaluated whether conductivity of cerebral tissue measured using magnetic resonance-based conductivity imaging (MRCI), which provides contrast derived from the concentration and mobility of ions within the imaged tissue, can reflect the severity of HIBI in the early hours after cardiac arrest. METHODS: Fourteen minipigs were resuscitated after 5 min or 12 min of untreated cardiac arrest. MRCI was performed at baseline and at 1 h and 3.5 h after return of spontaneous circulation (ROSC). RESULTS: In both groups, the conductivity of cerebral tissue significantly increased at 1 h after ROSC compared with that at baseline (P = 0.031 and 0.016 in the 5-min and 12-min groups, respectively). The increase was greater in the 12-min group, resulting in significantly higher conductivity values in the 12-min group (P = 0.030). At 3.5 h after ROSC, the conductivity of cerebral tissue in the 12-min group remained increased (P = 0.022), whereas that in the 5-min group returned to its baseline level. CONCLUSIONS: The conductivity of cerebral tissue was increased in the first hours after ROSC, and the increase was more prominent and lasted longer in the 12-min group than in the 5-min group. Our findings suggest the promising potential of MRCI as a tool to estimate the severity of HIBI in the early hours after cardiac arrest.

Late Awakening Is Common in Settings Without Withdrawal of Life-Sustaining Therapy in Out-of-Hospital Cardiac Arrest Survivors Who Undergo Targeted Temperature Management.

OBJECTIVES: We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. DESIGN: Retrospective analysis of the Korean Hypothermia Network Pro registry. SETTING: Multicenter ICU. PATIENTS: Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. CONCLUSIONS: Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

Role of electrocardiogram findings in predicting 48-h mortality in patients with traumatic brain injury.

OBJECTIVE: Electrocardiogram (ECG) patterns can change, especially in patients with central nervous system disorders such as spontaneous subarachnoid hemorrhage. However, the association between the prognosis of traumatic brain injury (TBI) and ECG findings is unknown. Therefore, this study aimed to compare and to analyze ECG findings to predict early mortality in patients with TBI. METHODS: This retrospective observational study included patients with severe trauma and TBI who were admitted to the emergency department (ED) between January 2018 and December 2020. TBI was defined as an abbreviated injury scale score of the head of ≥3. We examined ECG findings, including PR prolongation (≥ 200 ms), QRS complex widening (≥ 120 ms), corrected QT interval prolongation (QTP, ≥ 480 ms), ST-segment elevation, and ST-segment depression (STD) at ED arrival. The primary outcome was 48-h mortality. RESULTS: Of the total patients with TBI, 1024 patients were included in this study and 48-h mortality occurred in 89 patients (8.7%). In multivariate analysis, QTP (odds ratio [OR], 2.017; confidence interval [CI], 1.203-3.382) and STD (OR, 8.428; 95% CI, 5.019-14.152) were independently associated with 48-h mortality in patients with TBI. The areas under the curve (AUCs) of the revised trauma score (RTS), injury severity score (ISS), QTP, STD, and the combination of QTP and STD were 0.790 (95% CI, 0.764-0.815), 0.632 (95% CI, 0.602-0.662), 0.605 (95% CI, 0.574-0.635), 0.723 (95% CI, 0.695-0.750), and 0.786 (95% CI, 0.759-0.811), respectively. The AUC of the combination of QTP and STD significantly differed from that of ISS, QTP, and STD, but not RTS. CONCLUSION: Based on the ECG findings, QTP and STD were associated with 48-h mortality in patients with TBI.

Supranormal arterial oxygen tension only during the first six hours after cardiac arrest is associated with unfavourable outcomes.

BACKGROUND: Multiple studies have investigated the association between hyperoxaemia following cardiac arrest (CA) and unfavourable outcomes; however, they have yielded inconsistent results. Most previous studies quantified oxygen exposure without considering its timing or duration. We investigated the relationship between unfavourable outcomes and supranormal arterial oxygen tension (PaO2 ), commonly defined as PaO2 > 100 mmHg, at specific time intervals within 24 h following CA. METHODS: This retrospective observational study included 838 adult non-traumatic patients with CA. The first 24 h following CA were divided into four 6-h time intervals, and the first 6-h period was further divided into three 2-h segments. Multivariable logistic regression analyses were conducted to assess associations of the highest PaO2 and time-weighted average PaO2 (TWA-PaO2 ) values at each time interval with unfavourable outcomes at hospital discharge (cerebral performance categories 3-5). RESULTS: The highest PaO2 (p = .028) and TWA-PaO2 (p = .022) values during the 0-6-h time interval were significantly associated with unfavourable outcomes, whereas those at time intervals beyond 6 h were not. The association was the strongest at supranormal PaO2 values within the 0-2-h time interval, becoming significant at PaO2 values ≥ 150 mmHg. During the first 6 h, longer time spent at ≥150 mmHg of PaO2 was associated with an increased risk of unfavourable outcomes (p = .038). The results were consistent across several sensitivity analyses. CONCLUSION: Supranormal PaO2 during but not after the first 6 h following cardiac arrest was independently associated with unfavourable outcomes.

Analysis of Factors Affecting Emergency Physicians' Attitudes toward Deceased Organ & Tissue Donation.

BACKGROUND: This study aimed to investigate differences in knowledge, and attitudes toward deceased organ and tissue donation of emergency physicians. Additionally, we analyzed factors affecting the attitudes toward deceased organ and tissue donation. METHODS: We conducted a survey of specialists and residents registered with the Korean Society of Emergency Medicine in December 2020. The respondents' sex, age, position, personal registration for organ donation, experience of soliciting organ donation, participation in related education, knowledge, and attitude about brain death organ donation, and attitude toward stopping life-sustaining treatments were investigated. According to the characteristics of the respondents (specialists or residents, experience and education on organ and tissue donation), their knowledge and attitude toward deceased organ donation were compared. Stepwise hierarchical multiple regression analysis was used to investigate the factors affecting the attitudes toward deceased organ and tissue donation. RESULTS: Of the total 428 respondents, there were 292 emergency medicine specialists and 136 medical residents. Specialists and those who registered or wished to donate organs had higher knowledge and attitude scores regarding deceased organ and tissue donation. Those who had experience recommending organ and tissue donation more than 6 times had higher knowledge scores on deceased organ and tissue donation and higher overall scores in attitude. Those who received education from the Korean Organ Donation Agency had higher knowledge scores. Specialists, and those who wished to donate or had registered as organ donors and had a higher life-sustaining treatment attitude score and knowledge about deceased organ and tissue donation, had more positive attitudes toward deceased organ and tissue donation. CONCLUSION: For more potential deceased organ and tissue donors to be referred for donation, there should be continuous education for emergency physicians on brain-dead organ and tissue donation-related knowledge and procedures. In addition, institutional or systematic improvements that can lead to organ donation when deciding on the withdrawal of life-sustaining treatment should be considered.

Pralidoxime-Induced Potentiation of the Pressor Effect of Adrenaline and Hastened Successful Resuscitation by Pralidoxime in a Porcine Cardiac Arrest Model.

PURPOSE: Pralidoxime potentiated the pressor effect of adrenaline and facilitated restoration of spontaneous circulation (ROSC) after prolonged cardiac arrest. In this study, we hypothesised that pralidoxime would hasten ROSC in a model with a short duration of untreated ventricular fibrillation (VF). We also hypothesised that potentiation of the pressor effect of adrenaline by pralidoxime would not be accompanied by worsening of the adverse effects of adrenaline. METHODS: After 5 min of VF, 20 pigs randomly received either pralidoxime (40 mg/kg) or saline, in combination with adrenaline, during cardiopulmonary resuscitation (CPR). Coronary perfusion pressure (CPP) during CPR, and ease of resuscitation were compared between the groups. Additionally, haemodynamic data, severity of ventricular arrhythmias, and cerebral microcirculation were measured during the 1-h post-resuscitation period. Cerebral microcirculatory blood flow and brain tissue oxygen tension (PbtO2) were measured on parietal cortices exposed through burr holes. RESULTS: All animals achieved ROSC. The pralidoxime group had higher CPP during CPR (P = 0.014) and required a shorter duration of CPR (P = 0.024) and smaller number of adrenaline doses (P = 0.024). During the post-resuscitation period, heart rate increased over time in the control group, and decreased steadily in the pralidoxime group. No inter-group differences were observed in the incidences of ventricular arrhythmias, cerebral microcirculatory blood flow, and PbtO2. CONCLUSION: Pralidoxime improved CPP and hastened ROSC in a model with a short duration of untreated VF. The potentiation of the pressor effect of adrenaline was not accompanied by the worsening of the adverse effects of adrenaline.

Pralidoxime administered during cardiopulmonary resuscitation facilitates successful resuscitation in a pig model of cardiac arrest.

Pralidoxime is a common antidote for organophosphate poisoning; however, studies have also reported pralidoxime's pressor effect, which may facilitate the restoration of spontaneous circulation (ROSC) after cardiac arrest by improving coronary perfusion pressure (CPP). We investigated the immediate cardiovascular effects of pralidoxime in anaesthetised normal rats and the effects of pralidoxime administration during cardiopulmonary resuscitation (CPR) in a pig model of cardiac arrest. To evaluate the immediate cardiovascular effects of pralidoxime, seven anaesthetised normal rats received saline or pralidoxime (20 mg/kg) in a randomised crossover design, and the responses were determined using the conductance catheter technique. To evaluate the effects of pralidoxime administration during CPR, 22 pigs randomly received either 80 mg/kg of pralidoxime or an equivalent volume of saline during CPR. In the rats, pralidoxime significantly increased arterial pressure than saline (P = .044). The peak effect on arterial pressure was observed in the first minute. In a pig model of cardiac arrest, CPP during CPR was higher in the pralidoxime group than in the control group (P = .002). ROSC was attained in three animals (27.3%) in the control group and nine animals (81.8%) in the pralidoxime group (P = .010). Three animals (27.3%) in the control group and eight animals (72.2%) in the pralidoxime group survived the 6-hour period (P = .033). In conclusion, pralidoxime had a rapid onset of pressor effect. Pralidoxime administered during CPR led to significantly higher rates of ROSC and 6-hour survival by improving CPP in a pig model.

Association of plasma neutrophil gelatinase-associated lipocalin with acute kidney injury and clinical outcome in cardiac arrest survivors depends on the time of measurement.

PURPOSE: The optimal timing for measurement of neutrophil gelatinase-associated lipocalin (NGAL) level to predict acute kidney injury (AKI) and prognosis in cardiac arrest (CA) survivors has not been elucidated. We aimed to compare the diagnostic and prognostic performance of NGAL levels after return of spontaneous circulation (ROSC) and at 48 h after CA. METHODS: We included 231 adult cardiac arrest survivors who underwent targeted temperature management between May 2013 and December 2016. The primary outcome was stage 2 and 3 AKI (high stage AKI), and the secondary outcomes were in-hospital mortality and neurologic outcome. Sixty-one (26.4%) developed high stage AKI, 50 (21.6%) died, and 152 (65.8%) had a poor neurologic outcome. RESULTS: NGAL level at 48 h (0.876; 95% confidence interval [CI], 0.826-0.916) had a higher area under receiver operating characteristic curve than NGAL level after ROSC (0.694; 95% CI, 0.631-0.753). Both NGAL levels were independently associated with high stage AKI. NGAL level at 48 h (1.001; 95% CI, 1.000-1.002) remained a significant predictor for in-hospital mortality, while neither of the NGAL levels were independently associated with neurologic outcome. CONCLUSIONS: NGAL at 48 h after CA seems to be a robust predictor for high stage AKI and in-hospital mortality.

Comparison of propofol monotherapy and propofol combination therapy for sedation during gastrointestinal endoscopy: A systematic review and meta-analysis.

BACKGROUND AND AIM: Previous randomized controlled trials have reported conflicting findings comparing propofol combination therapy (PCT) with propofol monotherapy (PMT) for sedation of patients undergoing gastrointestinal endoscopy. Therefore, a systematic review was carried out to compare the efficacy and safety of PCT and PMT in such patients. METHODS: We searched MEDLINE, EMBASE and CENTRAL databases to identify all randomized controlled trials that compared the efficacy and safety of PCT and PMT for sedation of patients undergoing gastrointestinal endoscopy. Primary endpoints were incidence of respiratory complications, hypotension and arrhythmia, dose of propofol used, and recovery time. Procedure duration and the satisfaction of patients and doctors were also evaluated. RESULTS: A total of 2250 patients from 22 studies were included in the final analysis. The combined analysis did not show any difference between PCT and PMT in the incidence of respiratory complications (risk ratio [RR], 0.80; 95% CI, 0.52 to 1.23; I2 = 58.34%), hypotension (RR, 1.06; 95% CI, 0.63 to 1.78; I2 = 72.13%), arrhythmia (RR,1.40; 95% CI, 0.74 to 2.64; I2 = 43.71%), recovery time (standardized mean difference [SMD], 0.16; 95% CI, -0.49 to 0.81; I2 = 95.9%), procedure duration (SMD, 0.04; 95% CI, -0.05 to 0.14; I2 = 0.0%), patient satisfaction (SMD, 0.13; 95% CI, -0.26 to 0.52; I2 = 89.63%) or doctor satisfaction (SMD, 0.01; 95% CI, -0.15 to 0.17; I2 = 0.00%). However, the dose of propofol used was significantly lower in PCT than in PMT (SMD, -1.38; 95% CI, -1.99 to -0.77; I2 = 97.70%). CONCLUSION: PCT showed comparable efficacy and safety to PMT with respect to respiratory complications, hypotension and arrhythmia, recovery time, procedure duration, patient satisfaction, and doctor satisfaction. However, the average dose of propofol used was higher in PMT.

Relationship Between Left Ventricle Position and Haemodynamic Parameters During Cardiopulmonary Resuscitation in a Pig Model.

BACKGROUND: From the viewpoint of cardiac pump theory, the area of the left ventricle (LV) subjected to compression increases as the LV lies closer to the sternum, possibly resulting in higher blood flow in patients with LV closer to the sternum. However, no study has evaluated LV position during cardiac arrest or its relationship with haemodynamic parameters during cardiopulmonary resuscitation (CPR). The objectives of this study were to determine whether the position of the LV relative to the anterior-posterior axis representing the direction of chest compression shifts during cardiac arrest and to examine the relationship between LV position and haemodynamic parameters during CPR. METHODS: Subcostal view echocardiograms were obtained from 15 pigs with the transducer parallel to the long axis of the sternum before inducing ventricular fibrillation (VF) and during cardiac arrest. Computed tomography was performed in three pigs to objectively observe LV position during cardiac arrest. LV position parameters including the shortest distance between the anterior-posterior axis and the mid-point of the LV chamber (DAP-MidLV), the shortest distance between the anterior-posterior axis and the LV apex (DAP-Apex), and the area fraction of the LV located on the right side of the anterior-posterior axis (LVARight/LVATotal) were measured. RESULTS: DAP-MidLV, DAP-Apex, and LVARight/LVATotal decreased progressively during untreated VF and basic life support (BLS), and then increased during advanced cardiovascular life support (ACLS). A repeated measures analysis of variance revealed significant time effects for these parameters. During BLS, the end-tidal carbon dioxide and systolic right atrial pressure were significantly correlated with the LV position parameters. During ACLS, systolic arterial pressure and systolic right atrial pressure were significantly correlated with DAP-MidLV and DAP-Apex. CONCLUSIONS: Left ventricular position changed significantly during cardiac arrest compared to the pre-arrest baseline. LV position during CPR had significant correlations with haemodynamic parameters.

Effect of ultrasound-guided phrenic nerve block on shoulder pain after laparoscopic cholecystectomy-a prospective, randomized controlled trial.

BACKGROUND: Post-laparoscopic shoulder pain (PLSP) frequently follows a laparoscopic cholecystectomy. A proposed mechanism for PLSP is the irritation or injury of the phrenic nerve by the CO2 pneumoperitoneum during laparoscopic surgery. Here, we investigated whether a phrenic nerve block (PNB), performed under ultrasound guidance, could reduce the incidence and severity of PLSP after laparoscopic cholecystectomy. METHOD: Sixty patients were randomized into two groups, with one group receiving PNB with 4 ml (30 mg) of 0.75% ropivacaine (group P, n = 28) and a control group (group C, n = 32). The existence and severity of PLSP were assessed for 2 days postoperatively. A pulmonary function test (PFT) and diaphragmatic excursion test were performed pre- and postoperatively. RESULTS: With ultrasound guidance, all PNBs were performed successfully in group P. In group P, the overall incidence and severity of PLSP decreased significantly. There were no significant differences in incisional pain, visceral pain, and analgesic requirements between the groups. Right-side diaphragmatic excursion decreased significantly in group P at 1 h postoperatively. The PFT results and respiratory discomfort assessed by a modified Borg's scale were not different significantly between the groups. CONCLUSION: Based on these findings, ultrasound-guided PNB can prevent or reduce the PLSP without clinically significant respiratory discomfort.

Effects of a Lidocaine-Loaded Poloxamer/Alginate/CaCl2 Mixture on Postoperative Pain and Adhesion in a Rat Model of Incisional Pain.

BACKGROUND: Pain and adhesion are problematic issues after surgery. Lidocaine has analgesics and anti-inflammatory properties, and poloxamer/alginate/CaCl2 (PACM) is a known antiadhesive agent. We hypothesized that the novel combination of lidocaine as chemical barrier and PACM as physical barrier would be beneficial for both postoperative pain and adhesion. The purpose of this study was to investigate the effects of lidocaine-loaded PACM in a rat model of incisional pain. Primary outcome was to evaluate between-group differences for the mechanical withdrawal threshold (MWT) measured by von Frey filament in various concentrations of lidocaine-loaded PACM applied, PACM applied, and sham-operated groups. METHODS: Male Sprague-Dawley rats were used for the postoperative pain model. After plantar incision and adhesion formation, 0.5%, 1%, 2%, and 4% lidocaine-loaded PACM, PACM only, nothing, and 4% lidocaine only were applied at the incision site in groups PL0.5, PL1, PL2, PL4, P, S, and L4, respectively. MWT using a von Frey filament and serum levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and high-sensitivity C-reactive protein were measured. Rats were euthanized 2 weeks after surgery, and inflammation and fibrosis were assessed with microscopy. Data were analyzed using the Kruskal-Wallis test, multivariate analysis of variance, and linear mixed-effect model. To compare MWT at each time point, analysis of variance with Bonferroni correction was used. RESULTS: Multivariate analysis of variance showed that 4% lidocaine-loaded PACM significantly raised the MWT up to 6 and 8 hours after surgery compared with lidocaine-unloaded groups S and P, respectively; 2% lidocaine-loaded PACM significantly increased the MWT at 4 hours after surgery compared with groups S and C. Linear mixed-effect model showed that the MWT (estimated difference in means [95% confidence interval]) was significantly increased in groups PL2 and PL4 (6.58 [2.52-10.63], P = .002; 11.46 [7.40-15.51], P < .001, respectively) compared with group P. Inflammation and fibrosis seen on microscopic evaluation were significantly decreased in groups PL2 and PL4 compared with group S. Four percent of lidocaine only showed a significant reduction in inflammation. Serum levels of tumor necrosis factor-α, IL-1ß, IL-6, and high-sensitivity C-reactive protein were decreased in lidocaine-loaded groups compared with group S or P at 1, 2, and 48 hours, and 2 weeks after surgery, respectively. CONCLUSIONS: Lidocaine-loaded PACM reduced postoperative pain, and lidocaine strengthened the antiadhesive effect of PACM.

The association of body mass index with outcomes and targeted temperature management practice in cardiac arrest survivors.

PURPOSE: Obesity is a well-known risk factor in various health conditions. We analyzed the association between obesity and clinical outcomes, and its effect on targeted temperature management (TTM) practice for cardiac arrest survivors by calculating and classifying their body mass indexes (BMIs). METHODS: We conducted a retrospective data analysis of adult comatose cardiac arrest survivors treated with TTM from 2008 to 2015. BMI was calculated and the cohort was divided into four categories based on the cut-off values of 18.5, 23.0, and 27.5kgm-2. The primary outcome was six-month mortality and the secondary outcomes were neurologic outcome at hospital discharge, cooling rate, and rewarming rate. RESULTS: The study included 468 patients. Poor neurologic outcome at discharge and six-month mortality were reported in 311 (66.5%) and 271 (57.9%) patients, respectively. A multivariate logistic analysis showed that an overweight compared to normal BMI was associated with lower probability of six-month mortality (odds ratio [OR], 0.481; 95% confidence interval [CI], 0.274-0.846; p=0.011) and poor neurologic outcome at discharge (OR, 0.482; 95% CI, 0.258-0.903; p=0.023). BMI correlated with cooling rate (B, -0.073; 95% CI, -0.108 to -0.039; p<0.001), but had no association with rewarming rate (B, 0.003; 95% CI, -0.001-0.008; p=0.058). CONCLUSION: Overweight BMI compared to normal BMI classification was found to be associated with lower six-month mortality and poor neurologic outcome at discharge in cardiac arrest survivors treated with TTM. Higher BMI correlated with a slower induction rate.

Disseminated intravascular coagulation is associated with the neurologic outcome of cardiac arrest survivors.

PURPOSE: We aimed to examine the serial changes in coagulofibrinolytic markers that occurred after the restoration of spontaneous circulation (ROSC) in cardiac arrest patients, who were treated with targeted temperature management (TTM). We also evaluated the association between the disseminated intravascular coagulation (DIC) score and clinical outcomes. METHODS: This was a single-centre, retrospective observational study that included cardiac arrest patients who were treated with TTM from May 2012 to December 2015. The prothrombin time (PT) and partial thromboplastin time (PTT), along with the levels of fibrinogen, fibrin degradation products (FDP), and D-dimer were obtained after ROSC and on day 1, 2, and 3. The DIC score was calculated after ROSC. The primary outcome was the neurologic outcome at discharge and the secondary outcome was the 6-month mortality. RESULTS: This study included 317 patients. Of these, 222 (70.0%) and 194 (61.2%) patients had a poor neurologic outcome at discharge and 6-month mortality, respectively. The PT, PTT, and fibrinogen level significantly increased over time, while the FDP and D-dimer levels decreased during first three days after ROSC. Multivariate logistic analyses revealed that the DIC score remained a significant predictor for poor neurologic outcome (odds ratio [OR], 1.800; 95% confidence interval [CI], 1.323-2.451) and 6-month mortality (OR, 1.773; 95% CI, 1.307-2.405). CONCLUSION: The activity of coagulation and fibrinolysis decreased over time. An increased DIC score was an independent prognostic factor for poor neurologic outcome and 6-month mortality.

Clinical Efficacy of Intravenous Lidocaine for Thyroidectomy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Systemic lidocaine has analgesic and anti-inflammatory effects. The purpose of this prospective, randomized, double-blind study was to evaluate the effects of intravenous lidocaine on pain following thyroidectomy. METHODS: Fifty-eight adult patients scheduled for total thyroidectomy were randomly allocated to receive a 1.5 mg/kg lidocaine bolus followed by a 2 mg/kg/h infusion during surgery, or the same volume of normal saline (control). After thyroidectomy, we evaluated postoperative pain, nausea, fentanyl consumption, frequency of pushing the button (FPB) for patient-controlled analgesia (PCA), High-sensitivity C-reactive protein (hs-CRP) in serum, and patient satisfaction scores regarding the recovery process. RESULTS: Postoperative pain and nausea scores were significantly lower in the lidocaine group for the first 4 h following thyroidectomy, compared to the control group. Fentanyl consumption and FPB for the PCA were also significantly reduced in the lidocaine group for 4 h following thyroidectomy, and hs-CRP was significantly less in the lidocaine group at postoperative days 1 and 3. Furthermore, satisfaction scores were significantly higher in the lidocaine group compared to the control group. CONCLUSIONS: Intravenous lidocaine effectively reduced postoperative pain and nausea following thyroidectomy as well as improved the quality of recovery. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT01608360.

The Effectiveness of Midazolam for Preventing Postoperative Nausea and Vomiting: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous randomized controlled trials regarding the effectiveness of perioperative midazolam in preventing postoperative nausea and vomiting (PONV) have produced conflicting results. Consequently, the present systematic review was performed to assess the effect of perioperative administration of midazolam on PONV. METHODS: The MEDLINE®, Embase, and Cochrane Central Register of Controlled Trials databases were searched to identify all randomized controlled trials that investigated the effectiveness of midazolam under general anesthesia. The primary end points were defined as postoperative nausea (PON), postoperative vomiting (POV), and PONV. RESULTS: From 16 studies, 1433 patients were included in the final analysis. Compared with the control group, patients who received midazolam showed a lower overall incidence of PON (risk ratio [RR], 0.51; 95% confidence interval [CI], 0.40-0.65; I = 35%; number needed to treat [NNT] = 6; number of included studies [n] = 11), POV (RR, 0.46; 95% CI, 0.33-0.65; I = 0%; NNT = 8; n = 10), and PONV (RR, 0.45; 95% CI, 0.36-0.57; I = 31%; NNT = 3; n = 7). CONCLUSIONS: Perioperative administration of midazolam was effective in preventing PON, POV, and PONV.

Prevalence and risk factors for central diabetes insipidus in cardiac arrest survivor treated with targeted temperature management.

PURPOSE: Central diabetes insipidus (CDI) is a marker of severe brain injury. Here we aimed to investigate the prevalence and risk factors of CDI in cardiac arrest survivors treated with targeted temperature management (TTM). METHODS: This retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM between 2008 and 2014. Central diabetes insipidus was confirmed if all of the following criteria were met: urine volume >50 cc kg(-1) d(-1), serum osmolarity >300 mmol/L, urine osmolarity <300 mmol/L, and serum sodium >145 mEq/L. The primary outcome was the incidence of CDI. RESULTS: Of the 385 included patients, 45 (11.7%) had confirmed central CDI. Univariate analysis showed that younger age, nonwitness of collapse, nonshockable rhythm, a high incidence of asphyxia arrest, longer downtime, and lower initial core temperature were associated with CDI development. Patients with CDI had a higher incidence of poor neurologic outcomes at discharge and higher in-hospital mortality rate (20/45 vs 76/340, P= .001) as well as 180-day mortality (44/45 vs 174/340, P< .001). Multivariate analysis revealed that age (odds ratio [OR], 0.963; 95% confidence interval [CI], 0.942-0.984), shockable rhythm (OR, 0.077; 95% CI, 0.009-0.662), downtime (OR, 1.025; 95% CI, 1.006-1.044), and asphyxia etiology (OR, 6.815; 95% CI, 2.457-18.899) were independently associated with CDI development. CONCLUSION: Central diabetes insipidus developed in 12% of cardiac arrest survivors treated with TTM, and those with CDI showed poor neurologic outcomes and high mortality rates. Younger age, nonshockable rhythm, long downtime, and asphyxia arrest were significant risk factors for development of CDI.

Comparison of hemodynamic response to tracheal intubation and postoperative pain in patients undergoing closed reduction of nasal bone fracture under general anesthesia: a randomized controlled trial comparing fentanyl and oxycodone.

BACKGROUND: The present study aimed to compare the intravenous bolus effect of oxycodone and fentanyl on hemodynamic response after endotracheal intubation and postoperative pain in patients undergoing closed reduction of nasal bone fracture. METHODS: In this prospective randomized double-blinded study, 64 patients undergoing closed reduction of nasal bone fracture were randomized into one of two groups: the fentanyl group (Group F) or the oxycodone group (Group O). Each drug (fentanyl 2 mcg/kg in Group F and oxycodone 0.2 mg/kg in Group O) was administered prior to the induction of general anesthesia. Hemodynamic changes after endotracheal intubation and postoperative pain were then measured in both groups. RESULTS: There was no significant difference in the change in mean arterial pressure and heart rate between pre-induction and post-intubation in both Groups F and O (P > 0.05). Postoperative pain in Group O was milder than that in Group F (P < 0.001); however, time to awakening from the end of operation was shorter in Group F (P = 0.012). CONCLUSION: In patients undergoing closed reduction of nasal bone fracture, oxycodone attenuates hemodynamic response to endotracheal intubation similar to fentanyl. However, oxycodone is more effective than fentanyl in improving postoperative pain. TRIAL REGISTRATION: Clinical Research Information Service (Trial registry number: KCT0001153 ) on 3 July, 2014.

Antinociceptive Effects of Ginsenoside Rg3 in a Rat Model of Incisional Pain.

BACKGROUND: Ginsenoside Rg3 is an extract of total ginseng saponins, which accounts for 4.7% of all saponins. This study aimed to identify the mechanisms of the antinociceptive effects of ginsenoside Rg3. METHODS: Rats were randomly divided into six groups, which were treated with vehicle or 0.5, 1, 1.5, 2, or 4 mg/kg of ginsenoside Rg3 intraperitoneally 2 h after a plantar incision was made. To evaluate the mechanisms of antinociceptive effects, the rats were intraperitoneally injected with naloxone 5 mg/kg, atropine 1 mg/kg, yohimbine 2 mg/kg, mecamylamine 1 mg/kg, prazosin 1 mg/kg, and dexmedetomidine 5 µg/kg. Hyperalgesia produced by the plantar incision was assessed using von Frey filaments 1 day before the incision (BI) and 2 h after the plantar incision (AP); this measurement was repeated at 15, 30, 45, 60, 80, 100 and 120 min, and 24 and 48 h after the injection of ginsenoside Rg3. Serum interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) levels were measured 1 day before incision and 120 min, 24 h, and 48 h after the injection of ginsenoside Rg3 or vehicle. RESULTS: The mechanical withdrawal threshold (MWT) significantly increased in the group that received ginsenoside Rg3. The dose-MWT response showed a curvilinear, bell-shaped relationship. The maximum MWT was found with the administration of ginsenoside Rg3 at 1.5 mg/kg; MWT decreased to 2 and 4 mg/kg. Yohimbine diminished the analgesic effect of ginsenoside Rg3. Prazosin and dexmedetomidine increased the analgesic effect of ginsenoside Rg3. IL-1ß and IL-6 appeared significantly lower relative to control group. CONCLUSIONS: Ginsenoside Rg3 has an analgesic effect with a curvilinear dose-response relationship. Alpha 2 adrenergic receptor appeared to be related to the analgesic effect of ginsenoside Rg3. Also, the anti-inflammatory effect of ginsenoside Rg3 could be related to its analgesic effect.