60 research outputs found
The nondepolarizing, normokalemic cardioplegia formulation adenosine-lidocaine (adenocaine) exerts anti-neutrophil effects by synergistic actions of its components
ObjectiveA new strategy of normothermic cardioplegia based on the combination of adenosine and lidocaine (adenocaine; Hibernation Therapeutics Global Ltd, Kilquade, Ireland) achieves nondepolarized arrest at normokalemia. Both adenosine and lidocaine independently inhibit neutrophil (polymorphonuclear neutrophil; PMN) activity. However, whether adenocaine exerts greater anti-inflammatory effects is not known. We tested the hypothesis that adenocaine synergistically attenuates PMN functions.MethodsSuperoxide anion (O2â) generation: Isolated porcine PMNs were primed with cytochalasin B (5 Îźg/mL) and activated by N-formylmethionyl-leucyl-phenylalanine (100 nM). O2â release was quantified using lucigenin-enhanced chemiluminescence. Data were expressed as percent of stimulated control.ResultsBoth adenosine and lidocaine alone inhibited O2â production in a dose-dependent manner (adenosine reduced to 67% Âą 8.4% and 21% Âą 2.2% of maximal stimulation at 0.1 and 10 Îźmol/L, respectively, lidocaine reduced to 57.9% Âą 18.6% and 28% Âą 5% at 10 and 100 Îźmol/L, respectively). Adenocaine further reduced O2â generation in a synergistic manner. In addition, adenosine alone (0.1â10 Îźmol/L) inhibited O2â generation in primed but not activated PMNs, whereas lidocaine alone (1â100 Îźmol/L) inhibited O2â release in both primed and activated PMNs. Adenocaine further reduced O2â generation because of inhibition of both priming and activation stages. Both adenosine and lidocaine alone and adenocaine comparably inhibited platelet activating factorâinduced CD11 b/c surface expression on PMNs (flow cytometry), but adenocaine further suppressed both CD18 expression (to 47.4% Âą 9.7%) and PMN adherence (to 47.2% Âą 4.3%) compared with adenosine and lidocaine alone. Transmigration of calcein-acetyoxymethylâlabeled PMNs through transwells seeded with cultured coronary artery endothelial cells was reduced comparably by adenosine (to 80.1% Âą 6.7%) and adenocaine (67.3% Âą 9.6%).ConclusionsAdenocaine suppresses multiple PMN functions including O2â generation, adhesion molecule expression, PMN adherence, and transmigration. In addition to inducing nondepolarized arrest, adenocaine cardioplegia may exert cardioprotection by inhibiting PMN-mediated inflammatory responses
Adenosine, lidocaine and Mg^2+ improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model
Introduction
The combination of Adenosine (A), lidocaine (L) and Mg^2+ (M) (ALM) has demonstrated cardioprotective and resuscitative properties in models of cardiac arrest and hemorrhagic shock. This study evaluates whether ALM also demonstrates organ protective properties in an endotoxemic porcine model.
Methods
Pigs (37 to 42 kg) were randomized into: 1) Control (nâ=â8) or 2) ALM (nâ=â8) followed by lipopolysaccharide infusion (1 Îźgâkg^-1âh^-1) for five hours. ALM treatment consisted of 1) a high dose bolus (A (0.82 mg/kg), L (1.76 mg/kg), M (0.92 mg/kg)), 2) one hour continuous infusion (A (300 Îźgâkg^-1 âmin^-1), L (600 Îźgâkg^-1 âmin^-1), M (336 Îźgâkg^-1 âmin^-1)) and three hours at a lower dose (A (240âkg^-1âmin^-1), L (480 Îźgâkg^-1âmin^-1), M (268 Îźgâkg^-1 âmin^-1)); controls received normal saline. Hemodynamic, cardiac, pulmonary, metabolic and renal functions were evaluated.
Results
ALM lowered mean arterial pressure (Mean value during infusion period: ALM: 47 (95% confidence interval (CI): 44 to 50) mmHg versus control: 79 (95% CI: 75 to 85) mmHg, P <0.0001). After cessation of ALM, mean arterial pressure immediately increased (end of study: ALM: 88 (95% CI: 81 to 96) mmHg versus control: 86 (95% CI: 79 to 94) mmHg, Pâ=â0.72). Whole body oxygen consumption was significantly reduced during ALM infusion (ALM: 205 (95% CI: 192 to 217) ml oxygen/min versus control: 231 (95% CI: 219 to 243) ml oxygen/min, Pâ=â0.016). ALM treatment reduced pulmonary injury evaluated by PaO(2)/FiO(2) ratio (ALM: 388 (95% CI: 349 to 427) versus control: 260 (95% CI: 221 to 299), Pâ=â0.0005). ALM infusion led to an increase in heart rate while preserving preload recruitable stroke work. Creatinine clearance was significantly lower during ALM infusion but reversed after cessation of infusion. ALM reduced tumor necrosis factor-Îą peak levels (ALM 7121 (95% CI: 5069 to 10004) pg/ml versus control 11596 (95% CI: 9083 to 14805) pg/ml, Pâ=â0.02).
Conclusion
ALM infusion induces a reversible hypotensive and hypometabolic state, attenuates tumor necrosis factor-Îą levels and improves cardiac and pulmonary function, and led to a transient drop in renal function that was reversed after the treatment was stopped
Association between tracheal intubation during adult in-hospital cardiac arrest and survival
Importance
Tracheal intubation is common during adult in-hospital cardiac arrest, but little is known about the association between tracheal intubation and survival in this setting.
Objective
To determine whether tracheal intubation during adult in-hospital cardiac arrest is associated with survival to hospital discharge.
Design, Setting, and Participants
Observational cohort study of adult patients who had an in-hospital cardiac arrest from January 2000 through December 2014 included in the Get With The GuidelinesâResuscitation registry, a US-based multicenter registry of in-hospital cardiac arrest. Patients who had an invasive airway in place at the time of cardiac arrest were excluded. Patients intubated at any given minute (from 0-15 minutes) were matched with patients at risk of being intubated within the same minute (ie, still receiving resuscitation) based on a time-dependent propensity score calculated from multiple patient, event, and hospital characteristics.
Exposure
Tracheal intubation during cardiac arrest.
Main Outcomes and Measures
The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC) and a good functional outcome. A cerebral performance category score of 1 (mild or no neurological deficit) or 2 (moderate cerebral disability) was considered a good functional outcome.
Results
The propensity-matched cohort was selected from 108âŻ079 adult patients at 668 hospitals. The median age was 69 years (interquartile range, 58-79 years), 45âŻ073 patients (42%) were female, and 24âŻ256 patients (22.4%) survived to hospital discharge. Of 71âŻ615 patients (66.3%) who were intubated within the first 15 minutes, 43âŻ314 (60.5%) were matched to a patient not intubated in the same minute. Survival was lower among patients who were intubated compared with those not intubated: 7052 of 43âŻ314 (16.3%) vs 8407 of 43âŻ314 (19.4%), respectively (risk ratio [RR]â=â0.84; 95% CI, 0.81-0.87; Pâ<â.001). The proportion of patients with ROSC was lower among intubated patients than those not intubated: 25âŻ022 of 43âŻ311 (57.8%) vs 25âŻ685 of 43âŻ310 (59.3%), respectively (RRâ=â0.97; 95% CI, 0.96-0.99; Pâ<â.001). Good functional outcome was also lower among intubated patients than those not intubated: 4439 of 41âŻ868 (10.6%) vs 5672 of 41âŻ733 (13.6%), respectively (RRâ=â0.78; 95% CI, 0.75-0.81; Pâ<â.001). Although differences existed in prespecified subgroup analyses, intubation was not associated with improved outcomes in any subgroup.
Conclusions and Relevance
Among adult patients with in-hospital cardiac arrest, initiation of tracheal intubation within any given minute during the first 15 minutes of resuscitation, compared with no intubation during that minute, was associated with decreased survival to hospital discharge. Although the study design does not eliminate the potential for confounding by indication, these findings do not support early tracheal intubation for adult in-hospital cardiac arrest
Senicapoc treatment in COVID-19 Patients with Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial
BACKGROUND: The aim of the current study was to determine if treatment with senicapoc, improves the PaO(2)/FiO(2) ratio in patients with COVIDâ19 and severe respiratory insufficiency. METHODS: Investigatorâinitiated, randomized, openâlabel, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged âĽ18âyears and admitted to an ICU with severe respiratory insufficiency due to COVIDâ19. The intervention consisted of 50âmg enteral senicapoc administered as soon as possible after randomization and again after 24âh. Patients in the control group received standard care only. The primary outcome was the PaO(2)/FiO(2) ratio at 72âh. RESULTS: Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on nonâinvasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72âh was 62.1âng/ml (IQR 46.7â71.2). The primary outcome, PaO(2)/FiO(2) ratio at 72âh, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference â5.1 kPa [95% CI â10.2, â0.04] p =â.05). The 28âday mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06â2.07, p =â.26). CONCLUSIONS: Treatment with senicapoc resulted in a significantly lower PaO(2)/FiO(2) ratio at 72âh with no differences for other outcomes
Vasopressin and methylprednisolone for in-hospital cardiac arrest - Protocol for a randomized, double-blind, placebo-controlled trial
Goal-directed haemodynamic therapy during general anaesthesia for noncardiac surgery:a systematic review and meta-analysis
BACKGROUND: During general anaesthesia for noncardiac surgery, there remain knowledge gaps regarding the effect of goal-directed haemodynamic therapy on patient-centred outcomes. METHODS: Included clinical trials investigated goal-directed haemodynamic therapy during general anaesthesia in adults undergoing noncardiac surgery and reported at least one patient-centred postoperative outcome. PubMed and Embase were searched for relevant articles on March 8, 2021. Two investigators performed abstract screening, full-text review, data extraction, and bias assessment. The primary outcomes were mortality and hospital length of stay, whereas 15 postoperative complications were included based on availability. From a main pool of comparable trials, meta-analyses were performed on trials with homogenous outcome definitions. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). RESULTS: The main pool consisted of 76 trials with intermediate risk of bias for most outcomes. Overall, goal-directed haemodynamic therapy might reduce mortality (odds ratio=0.84; 95% confidence interval [CI], 0.64 to 1.09) and shorten length of stay (mean difference=â0.72 days; 95% CI, â1.10 to â0.35) but with low certainty in the evidence. For both outcomes, larger effects favouring goal-directed haemodynamic therapy were seen in abdominal surgery, very high-risk surgery, and using targets based on preload variation by the respiratory cycle. However, formal tests for subgroup differences were not statistically significant. Goal-directed haemodynamic therapy decreased risk of several postoperative outcomes, but only infectious outcomes and anastomotic leakage reached moderate certainty of evidence. CONCLUSIONS: Goal-directed haemodynamic therapy during general anaesthesia might decrease mortality, hospital length of stay, and several postoperative complications. Only infectious postoperative complications and anastomotic leakage reached moderate certainty in the evidence
Fraction of Inspired Oxygen During General Anesthesia for Non-Cardiac Surgery:Systematic Review and Meta-Analysis
BACKGROUND: Controversy exists regarding the effects of a high versus a low intraoperative fraction of inspired oxygen (FiO(2)) in adults undergoing general anesthesia. This systematic review and metaâanalysis investigated the effect of a high versus a low FiO(2) on postoperative outcomes. METHODS: PubMed and Embase were searched on March 22, 2022 for randomized clinical trials investigating the effect of different FiO(2) levels in adults undergoing general anesthesia for nonâcardiac surgery. Two investigators independently reviewed studies for relevance, extracted data, and assessed risk of bias. Metaâanalyses were performed for relevant outcomes, and potential effect measure modification was assessed in subgroup analyses and metaâregression. The evidence certainty was evaluated using GRADE. RESULTS: This review included 25 original trials investigating the effect of a high (mostly 80%) versus a low (mostly 30%) FiO(2). Risk of bias was intermediate for all trials. A high FiO(2) did not result in a significant reduction in surgical site infections (OR: 0.91, 95% CI 0.81â1.02 [p = .10]). No effect was found for all other included outcomes, including mortality (OR = 1.27, 95% CI: 0.90â1.79 [p = .18]) and hospital length of stay (mean difference = 0.03âdays, 95% CI â0.25 to 0.30 [p = .84). Results from subgroup analyses and metaâregression did not identify any clear effect modifiers across outcomes. The certainty of evidence (GRADE) was rated as low for most outcomes. CONCLUSIONS: In adults undergoing general anesthesia for nonâcardiac surgery, a high FiO(2) did not improve outcomes including surgical site infections, length of stay, or mortality. However, the certainty of the evidence was assessed as low
Association of beta-blockers and first-registered heart rhythm in out-of-hospital cardiac arrest: real-world data from population-based cohorts across two European countries
AIMS: Conflicting results have been reported regarding the effect of beta-blockers on first-registered heart rhythm in out-of-hospital cardiac arrest (OHCA). We aimed to establish whether the use of beta-blockers influences first-registered rhythm in OHCA. METHODS AND RESULTS: We included patients with OHCA of presumed cardiac cause from two large independent OHCA-registries from Denmark and the Netherlands. Beta-blocker use was defined as exposure to either non-selective beta-blockers, β1-selective beta-blockers, or Îą-β-dual-receptor blockers within 90âdays prior to OHCA. We calculated odds ratios (ORs) for the association of beta-blockers with first-registered heart rhythm using multivariable logistic regression. We identified 23 834 OHCA-patients in Denmark and 1584 in the Netherlands: 7022 (29.5%) and 519 (32.8%) were treated with beta-blockers, respectively. Use of non-selective beta-blockers, but not β1-selective blockers, was more often associated with non-shockable rhythm than no use of beta-blockers [Denmark: OR 1.93, 95% confidence interval (CI) 1.48-2.52; the Netherlands: OR 2.52, 95% CI 1.15-5.49]. Non-selective beta-blocker use was associated with higher proportion of pulseless electrical activity (PEA) than of shockable rhythm (OR 2.38, 95% CI 1.01-5.65); the association with asystole was of similar magnitude, although not statistically significant compared with shockable rhythm (OR 2.34, 95% CI 0.89-6.18; data on PEA and asystole were only available in the Netherlands). Use of Îą-β-dual-receptor blockers was significantly associated with non-shockable rhythm in Denmark (OR 1.21; 95% CI 1.03-1.42) and not significantly in the Netherlands (OR 1.37; 95% CI 0.61-3.07). CONCLUSION: Non-selective beta-blockers, but not β1-selective beta-blockers, are associated with non-shockable rhythm in OHCA
Effect of Vasopressin and Methylprednisolone vs. Placebo on Long-Term Outcomes in Patients with In-Hospital Cardiac Arrest A Randomized Clinical Trial
- âŚ