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Aims: The clinical benefits of venoarterial extracorporeal membrane oxygenation (VA‐ECMO) for profound cardiogenic shock are well known. However, peripheral VA‐ECMO increases the left ventricular afterload, thus compromising myocardial recovery. Recent studies have revealed the benefit of left ventricular unloading using various methods applied at different times. The EARLY‐UNLOAD trial compares the clinical outcomes of early left ventricular unloading and conventional approach after VA‐ECMO. Methods and results: The EARLY‐UNLOAD trial is a single‐centre, open‐label, randomized trial that recruited 116 patients with cardiogenic shock undergoing VA‐ECMO. Patients meeting the inclusion criteria were randomized in a 1:1 ratio to two groups: routine left ventricular unloading via intracardiac echocardiography‐guided transseptal left atrial cannulation within 12 h of VA‐ECMO initiation or conventional approach that indicates rescue left ventricular unloading if clinical signs of an increased left ventricular afterload are present. The primary endpoint is the cumulative incidence of all‐cause death within 30 days, and patients will be followed‐up for 12 months. A key secondary endpoint is a composite measure of all‐cause death and rescue transseptal left atrial cannulation in the conventional group (suggestive of VA‐ECMO treatment failure) within 30 days. The enrolment of patients was finished in September 2022. Conclusions: The EARLY‐UNLOAD trial is the first randomized controlled trial to compare early left ventricular unloading and conventional approach after VA‐ECMO using the same unloading modality. The results could impact clinical practice to overcome the haemodynamic issues associated with VA‐ECMO. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aim Endoscopic retrograde cholangiopancreatography ( ERCP) has been increasingly performed in the elderly patients, yet little is known concerning objective criteria of safety. This study aimed to determine the potential predictors for the procedure-related outcomes. Methods Two hundred eighty-one patients older than 70 years who were indicated for ERCP (group A [ n = 195], 70-79 years of age; group B [ n = 86], ≥ 80 years of age) were prospectively enrolled and analyzed for the development of serious adverse events related to ERCP. Results ERCP was not performed in six patients at high risk for the procedure. There were significant differences between group A and B in Duke Activity Status Index ( DASI) (23.1 vs 14.9, P < 0.01) and Eastern Cooperative Oncology Group performance status (3 and 4, 49/195 vs 33/86, P < 0.05). Major ERCP-related complications (hypotension, severe bradycardia, hypoxia, myocardial infarction, cerebral infarction) occurred in five patients from group B and three from group A. Post- ERCP pancreatitis occurred in one patient from group A and bleeding in one from group B. In univariate analysis, old age (≥ 80 years), American Society of Anesthesiologists score ≥ 3, and DASI < 10 were statistically significant predictors for overall serious events related to ERCP. In the multivariate analysis, DASI < 10 (only manage to ambulate) was independent predictor for overall serious events related to ERCP. Conclusion DASI score is useful predictor for the feasibility assessment of safe ERCP in the elderly patients. [ABSTRACT FROM AUTHOR]

Background Cerebral blood flow (CBF) is impaired in the early phase after return of spontaneous circulation. Sodium nitroprusside (SNP) administration via intracranial subdural catheters improves cerebral cortical microcirculation. We determined whether the SNP treatment improves CBF in the subcortical tissue and evaluated the effects of this treatment on cerebral lactate. Methods and Results Sixty minutes after return of spontaneous circulation following 14 minutes of untreated cardiac arrest, 14 minipigs randomly received 4 mg SNP or saline via intracranial subdural catheters. CBF was measured in regions of interest within the cerebrum and thalamus using dynamic susceptibility contrast-magnetic resonance imaging. After return of spontaneous circulation, CBF was expressed as a percentage of the baseline value. In the saline group, the %CBF in the regions of interest within the cerebrum remained at approximately 50% until 3.5 hours after return of spontaneous circulation, whereas %CBF in the thalamic regions of interest recovered to approximately 73% at this time point. The percentages of the baseline values in the cortical gray matter and subcortical white matter were higher in the SNP group (group effect P =0.026 and 0.025, respectively) but not in the thalamus. The cerebral lactate/creatine ratio measured using magnetic resonance spectroscopy increased over time in the saline group but not in the SNP group (group-time interaction P =0.035). The thalamic lactate/creatine ratio was similar in the 2 groups. Conclusions SNP administered via intracranial subdural catheters improved CBF not only in the cortical gray matter but also in the subcortical white matter. The CBF improvement by SNP was accompanied by a decrease in cerebral lactate.

Background Postischemic cerebral hypoperfusion has been indicated as an important contributing factor to secondary cerebral injury after cardiac arrest. We evaluated the effects of sodium nitroprusside administered via a subdural intracranial catheter on the microcirculation, oxygenation, and electrocortical activity of the cerebral cortex in the early postresuscitation period using a pig model of cardiac arrest. Methods and Results Twenty-nine pigs were resuscitated with closed cardiopulmonary resuscitation after 14 minutes of untreated ventricular fibrillation. Thirty minutes after restoration of spontaneous circulation, 24 pigs randomly received either 4 mg of sodium nitroprusside (IT-SNP group) or saline placebo (IT-saline group) via subdural intracranial catheters and were observed for 5 hours. The same dose of sodium nitroprusside was administered intravenously in another 5 pigs. Compared with the IT-saline group, the IT-SNP group had larger areas under the curve for tissue oxygen tension and percent changes of arteriole diameter and number of perfused microvessels from baseline (all P <0.05) monitored on the cerebral cortex during the 5-hour period, without severe hemodynamic instability. This group also showed faster recovery of electrocortical activity measured using amplitude-integrated electroencephalography. Repeated-measures analysis of variance revealed significant group-time interactions for these parameters. Intravenously administered sodium nitroprusside caused profound hypotension but did not appear to increase the cerebral parameters. Conclusions Sodium nitroprusside administered via a subdural intracranial catheter increased post-restoration of spontaneous circulation cerebral cortical microcirculation and oxygenation and hastened electrocortical activity recovery in a pig model of cardiac arrest. Further studies are required to determine its impact on the long-term neurologic outcomes.

Background We previously reported that pralidoxime facilitated restoration of spontaneous circulation by potentiating the pressor effect of epinephrine. We determined the optimal dose of pralidoxime during cardiopulmonary resuscitation and evaluated the involvement of α-adrenoceptors in its pressor action. Methods and Results Forty-four pigs randomly received 1 of 3 doses of pralidoxime (40, 80, or 120 mg/kg) or saline placebo during cardiopulmonary resuscitation, including epinephrine administration. Pralidoxime at 40 mg/kg produced the highest coronary perfusion pressure, whereas 120 mg/kg of pralidoxime produced the lowest coronary perfusion pressure. Restoration of spontaneous circulation was attained in 4 (36.4%), 11 (100%), 9 (81.8%), and 3 (27.3%) animals in the saline, 40, 80, and 120 mg/kg groups, respectively ( P <0.001). In 49 rats, arterial pressure response to 40 mg/kg of pralidoxime was determined after saline, guanethidine, phenoxybenzamine, or phentolamine pretreatment, and the response to 200 mg/kg pf pralidoxime was determined after saline, propranolol, or phentolamine pretreatment. Pralidoxime at 40 mg/kg elicited a pressor response. Phenoxybenzamine completely inhibited the pressor response, but guanethidine and phentolamine did not. The pressor response of pralidoxime was even greater after guanethidine or phentolamine pretreatment. Pralidoxime at 200 mg/kg produced an initial vasodepressor response followed by a delayed pressor response. Unlike propranolol, phentolamine eliminated the initial vasodepressor response. Conclusions Pralidoxime at 40 mg/kg administered with epinephrine improved restoration of spontaneous circulation rate by increasing coronary perfusion pressure in a pig model of cardiac arrest, whereas 120 mg/kg did not improve coronary perfusion pressure or restoration of spontaneous circulation rate. The pressor effect of pralidoxime was unrelated to α-adrenoceptors and buffered by its vasodepressor action mediated by sympathoinhibition.