Vascular limitations in blood pressure regulation with age in women: Insights from exercise and acute cardioselective ß-blockade.

Younger women rely on altering cardiac output ( Q ̇ $\dot{Q}$ ) to regulate blood pressure (BP). In contrast, older women rely more on altering vascular tone. However, evidence suggests that the ability to alter systemic vascular conductance (SVC) is diminished in older women. In the present study, cardioselective ß-blockade was utilized to diminish the relative contribution of Q ̇ $\dot{Q}$ to BP regulation and thereby evaluate age-related vascular limitations in women at rest and during large muscle dynamic exercise. Younger (n = 13, mean age 26.0 years) and older (n = 14, mean age 61.8 years) healthy women performed submaximal bouts of semi-recumbent cycling exercise at varying intensities while receiving an intravenous infusion of esmolol, a ß1-antagonist, or saline control in a repeated-measures crossover design. Q ̇ $\dot{Q}$ was attenuated during esmolol infusion, with greater reductions during exercise (moderate, -1.0 (95% CI, -1.6 to -0.5) L/min, P < 0.001; heavy, -2.0 (95% CI, -2.6 to -1.5) L/min, P < 0.001) than seated rest (-0.5 (95% CI, -1.1 to 0.0) L/min, P = 0.048), and this reduction was not significantly different between age groups (P = 0.122). Older women exhibited a greater attenuation in mean arterial pressure (MAP) during esmolol (-7 (95% CI, -9 to -4) mmHg, P < 0.001) relative to younger women (-2 (95% CI, -5 to 0) mmHg, P = 0.071). These changes coincided with a greater reduction of SVC in the younger women during esmolol (-15 (95% CI, -20 to -10) mL/min/mmHg, P < 0.001) compared to older women (-3 (95% CI, -9 to 2) mL/min/mmHg, P = 0.242). Together, these findings provide evidence that older, postmenopausal women have a diminished ability to adjust SVC in order to regulate MAP.

The role of esmolol in sepsis: a meta-analysis based on randomized controlled trials.

BACKGROUND: Sepsis is associated with a high incidence and mortality and poses a significant challenge to the treatment. Although esmolol has shown promise in sepsis treatment, its efficacy and safety remain contentious. This meta-analysis aims to clarify the role of esmolol in sepsis management. METHODS: PubMed, Embase, Web of Science, Cochrane library, clinicaltrials.gov and the Chinese Clinical Trial Registry were searched and references of relevant reviews and meta-analysis were also screened for appropriate studies. Keywords and free words of 'sepsis', 'esmolol' and 'randomized controlled trials' were used for search. Meta-analysis was performed using RevMan 5.3 software. RESULTS: Fifteen studies involving 1100 patients were included. Compared with the control group, patients receiving esmolol exhibited significantly decreased 28-day mortality (RR, 0.69; 95% CI, 0.60 to 0.81; P < 0.0001), heart rate (HR) (SMD, -1.15; 95% CI, -1.34 to -0.96; P < 0.0001), cardiac troponin I levels (cTnI) (SMD, -0.88; 95% CI, -1.13 to -0.64; P < 0.0001), length of intensive care unit (ICU) stay (SMD, -0.46; 95% CI, -0.62 to -0.3; P < 0.0001) and duration of mechanical ventilation (SMD, -0.28; 95% CI, -0.48 to -0.09; P = 0.004) and significantly increased central venous oxygen saturation (ScvO2) (SMD, 0.66; 95% CI, 0.44 to 0.88; P < 0.0001).While, esmolol had no significant influence on norepinephrine dosage (SMD, 0.08; 95% CI, -0.13 to 0.29; P = 0.46), mean arterial pressure (MAP) (SMD, 0.17; 95% CI, -0.07 to 0.4; P = 0.16), central venous pressure (CVP) (SMD, 0.16; 95% CI, -0.04 to 0.35; P = 0.11) and left ventricular ejection fraction (LVEF) (SMD, 0.21; 95% CI, -2.9 to 0.7; P = 0.41). CONCLUSION: Esmolol reduces 28-day mortality, length of ICU stay and duration of mechanical ventilation in sepsis patients. Furthermore, esmolol improves oxygen metabolism, mitigates myocardial injury and decreases heart rate without significantly affecting hemodynamic parameters. TRIAL REGISTRATION: This study was registered on the PROSPERO website (registration number: CRD42023484884).

Efficacy and Safety of Esmolol in Neonatal Cardiac Surgery with Cardiopulmonary Bypass (CPB) for d-Transposition of the Great Arteries (d-TGA).

OBJECTIVE: D-Transposition of the great arteries (d-TGA) is the most common congenital heart disease requiring surgical correction within the neonatal period. Sinus tachycardia often persists postoperatively, potentially affecting cardiac function. This study aimed to investigate the efficacy and safety of the short-acting beta-1-selective beta-blocker esmolol in controlling heart rate in neonatal cardiac surgery with cardiopulmonary bypass (CPB). METHODS: A retrospective cohort study was conducted on neonates undergoing surgery for d-TGA. The study cohort included 112 patients, divided into an esmolol intervention group (n = 57) and a control group (n = 55). Baseline characteristics, hemodynamic parameters and outcome measures were assessed. RESULTS: In the esmolol group, median heart rate at ICU admission was significantly higher compared to the control group (155 vs. 147 bpm, p = 0.018). After a median time of 11 h, heart rate was lower among the esmolol patients (135 vs. 144 bpm, p < 0.001). There were no differences in other hemodynamic parameters between the two groups. Patients treated with esmolol required longer catecholamine support while no difference regarding survival, duration of invasive ventilation and ICU stay were noticed. CONCLUSION: No relevant hemodynamic difference was seen between neonates treated with perioperative esmolol and the control group and outcome did not differ. This indicates non-inferiority of perioperative betablocker therapy in young age. Prospective and placebo-controlled assessment of perioperative esmolol therapy in neonates is needed.

Esmolol, vector change, and dose-capped epinephrine for prehospital ventricular fibrillation or pulseless ventricular tachycardia.

BACKGROUND: Refractory ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) cardiac arrest describes a subset of patients who do not respond to standard Advanced Cardiac Life Support (ACLS) interventions and are associated with poor outcomes. Esmolol administration and vector change defibrillation have shown promise in improving outcomes in these patients, however evidence is limited. OBJECTIVES: This study compares clinical outcomes between patients with prehospital refractory VF/pVT who received an Emergency Medical Service (EMS) bundle, comprised of esmolol administration, vector change defibrillation, and dose-capped epinephrine at 3 mg, to patients who received standard ACLS interventions. METHODS: This multicenter, retrospective, cohort study evaluated medical records between October 18, 2017 and March 15, 2022. Patients were enrolled if they experienced a prehospital cardiac arrest with the rhythm VF or pVT, had received at least three standard defibrillations, at least 3 mg of epinephrine, and 300 mg of amiodarone. Patients who received the EMS bundle after its implementation were compared to patients who received standard ACLS interventions prior to its implementation. The primary outcome was sustained return of spontaneous circulation (ROSC), defined as ROSC lasting 20 min without recurrence of cardiac arrest. Secondary outcomes included the incidence of any ROSC, survival to hospital arrival, survival at hospital discharge, and neurologically intact survival at hospital discharge. RESULTS: Eighty-three patients were included in the study. Thirty-six were included in the pre-EMS bundle group and 47 patients were included in the post-EMS bundle group. Patients in the pre-EMS bundle group achieved significantly higher rates of sustained ROSC (58.3% vs 17%, p < 0.001), any ROSC (66.7% vs 19.1%, p < 0.001), and survival to hospital arrival (55.6% vs 17%, p < 0.001). The rates of survival to hospital discharge (16.7% vs 6.4%, p = 0.17) and neurologically intact survival at hospital discharge (5.9% vs 4.3%, p = 1.00) were not significantly different between groups. CONCLUSIONS: Patients who received the EMS bundle achieved sustained ROSC significantly less often and were less likely to have pulses at hospital arrival. The incidence of neurologically intact survival was low and similar between groups.

A successful case of electrical storm rescue after acute myocardial infarction.

BACKGROUND: Electrical storm (ES) is a heterogeneous clinical emergency that can present with malignant ventricular arrhythmias such as ventricular fibrillation (VF), ventricular tachycardia (VT), requiring the need for cardiac defibrillation. ES is a life-threatening condition with a high mortality rate. Successfully managing ES in the setting of acute myocardial infarction (MI) is expected to be known by physicians on call to reduce in-hospital mortality. CASE PRESENTATION: A 57-year-old man presenting with acute onset chest pain was found to have an infero-posterior ST-segment elevation myocardial infarction (STEMI) complicated by acute right ventricular MI secondary to total occlusion of the proximal right coronary artery (RCA). The patient developed ES in the form of recurrent VF that was managed successfully with electrical defibrillation, antiarrhythmic therapy with amiodarone and esmolol, endotracheal intubation, sedation, electrolyte replacement, volume resuscitation, comfort care, psychological intervention, and percutaneous coronary intervention (PCI) of the occluded epicardial artery. With these interventions used in quick succession and with the aspiration of a massive RCA thrombus, the patient was reversed to hemodynamic stability, did not have further episodes of VF, and survived the index hospitalization. CONCLUSION: ES is a rare but fatal complication of acute MI. Residents on night shifts should be better prepared and equipped to deal with this rare condition. We hope our successful experience can benefit physicians on call who take care of acute MI patients that deteriorate with ES.

Esterases Involved in the Rapid Bioconversion of Esmolol after Intravenous Injection in Humans.

Esmolol is indicated for the acute and temporary control of ventricular rate due to its rapid onset of action and elimination at a rate greater than cardiac output. This rapid elimination is achieved by the hydrolysis of esmolol to esmolol acid. It has previously been reported that esmolol is hydrolyzed in the cytosol of red blood cells (RBCs). In order to elucidate the metabolic tissues and enzymes involved in the rapid elimination of esmolol, a hydrolysis study was performed using different fractions of human blood and liver. Esmolol was slightly hydrolyzed by washed RBCs and plasma proteins while it was extensively hydrolyzed in plasma containing white blood cells and platelets. The negligible hydrolysis of esmolol in RBCs is supported by its poor hydrolysis by esterase D, the sole cytosolic esterase in RBCs. In human liver microsomes, esmolol was rapidly hydrolyzed according to Michaelis-Menten kinetics, and its hepatic clearance, calculated by the well-stirred model, was limited by hepatic blood flow. An inhibition study and a hydrolysis study using individual recombinant esterases showed that human carboxylesterase 1 isozyme (hCE1) is the main metabolic enzyme of esmolol in both white blood cells and human liver. These studies also showed that acyl protein thioesterase 1 (APT1) is involved in the cytosolic hydrolysis of esmolol in the liver. The hydrolysis of esmolol by hCE1 and APT1 also results in its pulmonary metabolism, which might be a reason for its high total clearance (170-285 mL/min/kg bodyweight), 3.5-fold greater than cardiac output (80.0 mL/min/kg bodyweight).

Prospective Clinical Trial Comparing IV Esmolol to IV Metoprolol in CT Coronary Angiography: Effect on Hemodynamic, Technical Parameters and Cost.

BACKGROUND: Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost. MATERIALS AND METHODS: Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality. RESULTS: Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status. CONCLUSION: Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.

The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines.

ß-blockers having specific affinities to ß-adrenergic receptors are routinely used to treat cardiovascular problems. Additionally, it has been demonstrated that these drugs can be effective in treating apoptosis-related diseases. The current study was conducted to investigate the cytotoxic and apoptotic effects of ß-1 selective esmolol, ß-2 selective ICI-118,551, and non-selective nadolol blockers on the cancerous and healthy lung cells. MTT test was used to evaluate cytotoxicity. Apoptotic actions were examined by using Annexin V-FITC/PI assay, JC-1 staining, ROS test, and the determination of the caspase-4 and -9, Bcl-2, Bax, Bax/Bcl-2, and JNK levels. Although the MRC-5 showed greater resistance than A549 cells, the ß-blockers at 150-250 µM exhibited different levels of cytotoxic effect on both lung cell lines. Esmolol was found to be the most ineffective blocker and the increases in Bcl-2 protein levels were appeared to be effective in resistance to this drug. The increases in reactive oxygen species (ROS) together with the increase in caspase-4 and Bax protein levels have been shown to play a role in ICI-118,551 induced lung cell death. Nadolol was the most effective blocker increasing the total apoptotic cell population in both lung cells, which was based on both mitochondrial and endoplasmic reticulum stress. When the selectivities of the ß-blockers are considered, it seems that ß-2 specific antagonism predominantly mediated the death of lung cells, and the overwhelming factors causing apoptosis mainly varied depending on the selectivity of the blockers.

Evaluation of esmolol for heart rate control in patients with acute aortic dissection.

PURPOSE: Acute aortic dissection is a serious and life-threatening condition that requires prompt, effective management. The purpose of this study was to evaluate the efficacy and safety of esmolol for heart rate control in patients with acute aortic dissection in the Emergency Department (ED). METHODS: This was a retrospective, descriptive analysis of patients treated for type A or type B acute aortic dissection in the ED at an academic medical center. The primary outcome was the proportion of patients achieving strict (≤60 bpm) or lenient (≤80 bpm) heart rate control within the first 60 min of therapy at the study site. The primary safety endpoint was the incidence of hypotension, defined as a systolic blood pressure of <90 mmHg or a mean arterial pressure of ≤60 mmHg. RESULTS: Of 266 patients screened, 40 patients met inclusion criteria. Thirty-three patients (82.5%) attained lenient rate control within the first 60 min of esmolol therapy. Eleven patients (27.5%) achieved a strict heart rate goal within the first 60 min of esmolol therapy. Five patients (12.5%) experienced an episode of hypotension during the first 3 h of esmolol therapy. CONCLUSION: In patients treated with esmolol infusion for acute aortic dissection, a lenient HR goal was achieved in most patients. In contrast, esmolol was not associated with attainment of strict HR control in most patients included in this sample. Further studies are warranted to evaluate the exact role of esmolol in acute aortic dissection in a larger patient population.

Esmolol in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether the administration of the ultra-short-acting ß-blocker esmolol in cardiac surgery could have a cardioprotective effect that translates into improved postoperative outcomes. DESIGN: Single-center, double-blinded, parallel-group randomized controlled trial. SETTING: A tertiary care referral center. PARTICIPANTS: Patients undergoing elective cardiac surgery with preoperative evidence of left ventricular end-diastolic diameter >60 mm and/or left ventricular ejection fraction <50%. INTERVENTIONS: Patients were assigned randomly to receive either esmolol (1 mg/kg as a bolus before aortic cross-clamping and 2 mg/kg mixed in the cardioplegia solution) or placebo in a 1:1 allocation ratio. MEASUREMENTS AND MAIN RESULTS: The primary composite endpoint of prolonged intensive care unit stay and/or in-hospital mortality occurred in 36/98 patients (36%) in the placebo group versus 27/102 patients (27%) in the esmolol group (p = 0.13). In the esmolol group, a reduction in the maximum inotropic score during the first 24 postoperative hours was observed (10 [interquartile range 5-15] v 7 [interquartile range 5-10.5]; p = 0.04), as well as a trend toward a reduction in postoperative low-cardiac-output syndrome (13/98 v 6/102; p = 0.08) and the rate of hospital admission at one year (26/95 v 16/96; p = 0.08). A trend toward an increase in the number of patients with ejection fraction ≥60% at hospital discharge also was observed (4/95 v 11/92; p = 0.06). CONCLUSIONS: In the present trial, esmolol as a cardioplegia adjuvant enhanced postoperative cardiac performance but did not reduce a composite endpoint of prolonged intensive care unit stay and/or mortality.

Resuscitating Resuscitation: Advanced Therapies for Resistant Ventricular Dysrhythmias.

BACKGROUND: More than 640,000 combined in-hospital and out-of-hospital cardiac arrests occur annually in the United States. However, survival rates and meaningful neurologic recovery remain poor. Although "shockable" rhythms (i.e., ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)) have the best outcomes, many of these ventricular dysrhythmias fail to return to a perfusing rhythm (resistant VF/VT), or recur shortly after they are resolved (recurrent VF/VT). OBJECTIVE: This review discusses 4 emerging therapies in the emergency department for treating these resistant or recurrent ventricular dysrhythmias: beta-blocker therapy, dual simultaneous external defibrillation, stellate ganglion blockade, and extracorporeal cardiopulmonary resuscitation. We discuss the underlying physiology of each therapy, review relevant literature, describe when these approaches should be considered, and provide evidence-based recommendations for these techniques. DISCUSSION: Esmolol may mitigate some of epinephrine's negative effects when used during resuscitation, improving both postresuscitation cardiac function and long-term survival. Dual simultaneous external defibrillation targets the region of the heart where ventricular fibrillation typically resumes and may apply a more efficient defibrillation across the heart, leading to higher rates of successful defibrillation. Stellate ganglion blocks, recently described in the emergency medicine literature, have been used to treat patients with recurrent VF/VT, resulting in significant dysrhythmia suppression. Finally, extracorporeal cardiopulmonary resuscitation is used to provide cardiopulmonary support while clinicians correct reversible causes of arrest, potentially resulting in improved survival and good neurologic functional outcomes. CONCLUSION: These emerging therapies do not represent standard practice; however, they may be considered in the appropriate clinical scenario when standard therapies are exhausted without success.

Systolic-dicrotic notch pressure difference can identify tachycardic patients with septic shock at risk of cardiovascular decompensation following pharmacological heart rate reduction.

BACKGROUND: During sepsis, heart rate (HR) reduction could be a therapeutic target, but identification of responders (non-compensatory tachycardia) and non-responders (compensatory for 'fixed' stroke volume [SV]) is challenging. We tested the ability of the difference between systolic and dicrotic pressure (SDPdifference), which reflects the coupling between myocardial contractility and a given afterload, in discriminating the origin of tachycardia. METHODS: In this post hoc analysis of 45 patients with septic shock with persistent tachycardia, we characterised features of haemodynamic response focusing on SDPdifference, classifying patients according to variations in arterial dP/dtmax after 4 h of esmolol administration to maintain HR <95 beats min-1. A cut-off value of 0.9 mm Hg ms-1 was used for group allocation. RESULTS: After reducing HR, arterial dP/dtmax remained above the cut-off in 23 patients, whereas it decreased below the cut-off in 22 patients (from 0.99 [0.37] to 0.63 [0.16] mm Hg ms-1; mean [SD], P<0.001). At baseline, patients with decreased dP/dtmax after esmolol had lower SDPdifference than those with higher dP/dtmax (40 [19] vs 53 [16] mm Hg, respectively; P=0.01). The SDPdifference remained unchanged after esmolol in the higher dP/dtmax group (49 [16] mm Hg), whereas it decreased significantly in patients with lower dP/dtmax (29 [11] mm Hg; P<0.001). In the latter, the HR reduction resulted in a significant cardiac output reduction with unchanged SV, whereas in patients with higher dP/dtmax SV increased (from 48 [12] to 67 [14] ml; P<0.001) with maintained cardiac output. CONCLUSIONS: A decrease in SDPdifference could discriminate between compensatory and non-compensatory tachycardia, revealing a covert loss of myocardial contractility not detected by conventional echocardiographic parameters and deteriorating after HR reduction with esmolol. CLINICAL TRIAL REGISTRATION: NCT02188888.

Effects of dexmedetomidine and esmolol on otoacoustic emissions during controlled hypotensive anesthesia: randomized clinical trial.

PURPOSE: The aim of this study was to investigate the ability of esmolol and dexmedetomidine to achieve controlled hypotension on cochlea by measuring otoacoustic emission and stapedius reflex. METHODS: In this prospective, double-blind pilot study, patients scheduled for elective tympanoplasty, rhinoplasty and endoscopic sinus surgery operation were randomly assigned to two groups, and received either dexmedetomidine (n=23) or esmolol (n=24) during surgery to maintain a mean arterial blood pressure between 55 and 65 mmHg. Distortion product otoacoustic emission tests (DPOAE) were performed 24 hours before and after the operation and during surgery (in the 20th and 40th minutes of the operation). RESULTS: In the intra-group comparison, a statistically significant decrease was present at t20 (2,000 and 4,000 Hz frequency band) and t40 (1,000 and 1,500 Hz) according to the baseline value in the dexmedetomidine group (n=23); in the esmolol group (n=24), a statistically significant decrease (relative to the baseline value) was also detected at t20 and t40 for the 1,000 Hz frequency band. No damage was found on stapes reflexes with the infusion of these drugs. CONCLUSIONS: Infusion of dexmedetomidine and esmolol decreased DPOAE levels during the operations, but DPOAE levels returned to normal in the postoperative period, and had no effect on stapes reflexes. Studies with larger groups of patients are needed to confirm these results in tympanoplasty and other surgeries.

Esmolol in the management of pre-hospital refractory ventricular fibrillation: A systematic review and meta-analysis.

BACKGROUND: Esmolol has been proposed as a viable adjunctive therapy for pre-hospital refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). OBJECTIVES: We performed a systematic review and meta-analysis to assess the effectiveness of esmolol on pre-hospital refractory VF/pVT, compared with standard of care. METHODS: MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for eligible studies. Two investigators independently extracted relevant data and assessed the methodological quality of each included study using the ROBINS-I tool. The quality of evidence for summary estimates was assessed according to GRADE guidelines. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome of interest were calculated. RESULTS: The search yielded 3253 unique records, of which two studies were found to be in accordance with the research purpose, totaling 66 patients, of whom 33.3% (n = 22) received esmolol. Additional evidence was provided in the paper but was not relevant to the analysis and was therefore not included. Esmolol was likely associated with an increased rate of survival to discharge (RR 2.82, 95% CI 1.01-7.93, p = 0.05) (GRADE: Very low) and survival with favorable neurological outcome (RR 3.44, 95% CI 1.11-10.67, p = 0.03) (GRADE: Very low). Similar results were found for return of spontaneous circulation (ROSC) (RR 2.63, 95% CI 1.37-5.07, p = 0.004) (GRADE: Very low) and survival to intensive care unit (ICU)/hospital admission (RR 2.63, 95% CI 1.37-5.07, p = 0.004) (GRADE: Very low). CONCLUSION: The effectiveness of esmolol for refractory VF/pVT remains unclear. Trial sequential analysis (TSA) indicates that the evidence is inconclusive and that further trials are required in order to reach a conclusion. Therefore, it is imperative to continue to accumulate evidence in order to obtain a higher level of scientific evidence.

The evolving role of novel treatment techniques in the management of patients with refractory VF/pVT out-of-hospital cardiac arrest.

STUDY OBJECTIVES: The purpose of this review is to provide a brief overview of new life-saving interventions and novel techniques that have been proposed as viable treatment options for patients presenting with refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a comprehensive literature search of PubMed recent, Medline and Embase databases via the Ovid interface and Google Scholar from inception to July 2019. Eligible studies were observational in nature reporting outcomes of extracorporeal membrane oxygenation (ECMO), esmolol, double sequential defibrillation (DSD), and stellate ganglion block (SGB). Two investigators conducted the literature search, study selection, and data extraction. Any disagreements were resolved by consensus. RESULTS: Our database search identified 5331 records. We included in our review 23 articles that met our inclusion criteria. The selected studies included 16 observational studies on ECMO, 2 observational studies on esmolol, and 5 observational studies on DSD. CONCLUSION: We would like to suggest that there is not enough evidence in the existing literature to support at large-scale the effects of these techniques in the treatment of refractory VF/pVT OHCA. Randomized studies are warranted to evaluate the significant effects of these approaches against the best current standard of care.

Selective beta-blocker esmolol improves cerebral cortex microcirculation in a swine ventricular fibrillation model.

OBJECTIVE: This study aimed to identify whether esmolol attenuates cerebral cortex microcirculation blood flow due to epinephrine in prolonged ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR), and may improve neurological prognosis. METHODS: Male pigs were randomized into the esmolol+epinephrine group (group EE), the epinephrine group (group EP), and the normal saline group (group NS) (n = 8 each group). Untreated VF for 8 minutes was induced in pigs. After CPR for 2 minutes, group EE received esmolol (500 µg/kg)+epinephrine (20 µg/kg), group EP received epinephrine 20 µg/kg, and group NS received 5 mL normal saline. Then, a 120 J electric shock was delivered. If the return of spontaneous circulation (ROSC) failed, epinephrine (20 µg/kg) was repeated in group EP and EE, followed by another 2 minutes of CPR, a 150 J electric shock was delivered every 2 minutes until ROSC. Cerebral microcirculation images were obtained at 0.5, 6, 12, and 24 hours by cranial windows after ROSC. Cerebral performance category scores and neurological deficit scores (NDS) were calculated. The frontal cortices were harvested after the animals were euthanized. RESULTS: The NDS, the perfused vessel density, and the microcirculatory flow index of group EE were better than other two groups. The morphology of endothelial cells in the group EE remained intact; however, it was destroyed in the group EP. CONCLUSIONS: Administration of esmolol with epinephrine may alleviate the impairment of cerebral microcirculation blood flow caused by the administration of epinephrine in prolonged VF and thereby improves neurological outcomes in a swine model.

The effect of intraoperative lidocaine versus esmolol infusion on postoperative analgesia in laparoscopic cholecystectomy: a randomized clinical trial.

BACKGROUND: As a part of multimodal analgesia for laparoscopic cholecystectomy, both intraoperative lidocaine and esmolol facilitate postoperative analgesia. Our objective was to compare these two emerging strategies that challenge the use of intraoperative opioids. We aimed to assess if intraoperative esmolol infusion is not inferior to lidocaine infusion for opioid consumption after laparoscopic cholecystectomy. METHODS: In this prospective, randomized, double-blind, non-inferiority clinical trial, 90 female patients scheduled for elective laparoscopic cholecystectomy received either intravenous (IV) lidocaine bolus 1.5 mg/kg at induction followed by an infusion (1.5 mg/ kg/h) or IV bolus of esmolol 0.5 mg/kg at induction followed by an infusion (5-15 µg/kg/min) till the end of surgery. Remaining aspect of anesthesia followed a standard protocol apart from no intraoperative opioid supplementation. Postoperatively, patients received either morphine or tramadol IV to maintain visual analogue scale (VAS) scores ≤3. The primary outcome was opioid consumption (in morphine equivalents) during the first 24 postoperative hours. Pain and sedation scores, time to first perception of pain and void, and occurrence of nausea/vomiting were secondary outcomes measured up to 24 h postoperatively. RESULTS: Two patients in each group were excluded from the analysis. The postoperative median (IQR) morphine equivalent consumption in patients receiving esmolol was 1 (0-1.5) mg compared to 1.5 (1-2) mg in lidocaine group (p = 0.27). The median pain scores at various time points were similar between the two groups (p > 0.05). More patients receiving lidocaine were sedated in the post-anesthesia care unit (PACU) than those receiving esmolol (p < 0.05); however, no difference was detected later. CONCLUSION: Infusion of esmolol is not inferior to lidocaine in terms of opioid requirement and pain severity in the first 24 h after surgery. Patients receiving lidocaine were more sedated during their stay in PACU than those receiving esmolol. TRIAL REGISTRATION: ClinicalTrials.gov - NCT02327923. Date of registration: December 31, 2014.

Esmolol Compared with Amiodarone in the Treatment of Recent-Onset Atrial Fibrillation (RAF): An Emergency Medicine External Validity Study.

BACKGROUND: Recent-onset atrial fibrillation (RAF) is the most frequent supraventricular dysrhythmia in emergency medicine. Severely compromised patients require acute treatment with injectable drugs OBJECTIVE: The main purpose of this external validity study was to compare the short-term efficacy of esmolol with that of amiodarone to treat severe RAF in an emergency setting. METHODS: This retrospective survey was conducted in mobile intensive care units by analyzing patient records between 2002 and 2013. We included RAF with (one or more) severity factors including: clinical shock, angina pectoris, ST shift, and very rapid ventricular rate. A blind matching procedure was used to constitute esmolol group (n = 100) and amiodarone group (n = 200), with similar profiles for age, gender, initial blood pressure, heart rate, severity factors, and treatment delay. The main outcome measure was the percentage of patients with a ventricular rate control defined as heart frequency ≤ 100 beats/min. More stringent (rhythm control) and more humble indicators (20% heart rate reduction) were analyzed at from 10 to 120 min after treatment initiation. RESULTS: Patient characteristics were comparable for both groups: age 66 ± 16 years, male 71%, treatment delay < 1 h 36%, 1-2 h 29%, > 2 h 35%, chest pain 61%, ST shift 62%, ventricular rate 154 ± 26 beats/min, and blood pressure 126/73 mm Hg. The superiority of esmolol was significant at 40 min (64% rate control with esmolol vs. 25% with amiodarone) and for all indicators from 10 to 120 min after treatment onset. CONCLUSION: In "real life emergency medicine," esmolol is better than amiodarone in the treatment of RAF.

Left ventricular dysfunction after two hours of polarizing or depolarizing cardioplegic arrest in a porcine model.

INTRODUCTION: This experimental study compares myocardial function after prolonged arrest by St. Thomas' Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas' Hospital No 2, both administered as cold oxygenated blood cardioplegia. METHODS: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples. RESULTS: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both). CONCLUSION: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB.

[Effect of esmolol in septic shock patients with tachycardia: a randomized clinical trial].

Objective: To investigate the effect of esmolol in septic shock patients with tachycardia. Methods: A prospective randomized controlled trial was conducted. Screening septic shock patients that admitted to Department of General Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from June 2016 to August 2017. After 24 h resuscitation therapy, 100 cases of septic shock patients with tachycardia (heart rate>100 bpm) were divided into esmolol group (n=50) and control group (n=50) with random number table. Patients in esmolol group accepted standard treatment plus esmolol injection with an initial dose of 25 mg/h. Heart rate target is 80 to 100 bpm. Patients in esmolol group continued to use esmolol for 7 days or to the day the patient left the ICU when the heart rate didn't achieve the target. Patients in control group were given standard treatment. Primary outcome was 28 d mortality. Secondary outcomes included heart rate, norepinephrine dosages, lactate level, inflammatory markers in per day during the trial; acute physiology and chronic health evaluation (APACHE Ⅱ) and sequential organ failure assessment (SOFA) on day 1, 3, 5, 7; length of hospital stay, length of mechanical ventilation, medication time of vasoactive agent. The data were compared with t test or rank sum test between the two groups. Results: The 28 d mortality of esmolol group and control group was 62%, 68%, respectively(χ(2)=0.529, P=0.529). Logistic regression analysis showed that primary heart rate (increase of 10 bpm, OR=1.568, 95%CI: 1.039-1.238, P=0.027), primary APACHEⅡ (OR=1.134, 95%CI: 1.026-1.239, P=0.005), integral heart rate (per 10 bpm, OR=2.207, 95%CI: 1.400-3.479, P=0.001) were independent risk factors for 28 d mortality. Compared with control group, the esmolol group had a lower heart rate on day 1-7; but over all, there was no statistically significant difference in heart rate between the two groups (P>0.05). There was no significant difference in total does of norepinephrine, lactate level, inflammatory markers, APACHE Ⅱ, SOFA, length of hospital stay between the two groups (all P>0.05). Conclusion: Tachycardia significantly increases the risk of death in patients with septic shock, esmolol may decrease the mortality by controlling heart rate.