Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.

BACKGROUND: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. INTERVENTIONS: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo. MAIN OUTCOME MEASURES: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author). RESULTS: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment. CONCLUSIONS: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.

In vivo tebuconazole administration impairs heart electrical function and facilitates the occurrence of dobutamine-induced arrhythmias: involvement of reactive oxygen species.

Tebuconazole (TEB), a widely used pesticide in agriculture to combat fungal infections, is commonly detected in global food, potable water, groundwater, and human urine samples. Despite its known in vivo toxicity, its impact on heart function remains unclear. In a 28-day study on male Wistar rats (approximately 100 g), administering 10 mg/kg/day TEB or a vehicle (control) revealed no effect on body weight gain or heart weight, but an increase in the infarct area in TEB-treated animals. Notably, TEB induced time-dependent changes in in vivo electrocardiograms, particularly prolonging the QT interval after 28 days of administration. Isolated left ventricular cardiomyocytes exposed to TEB exhibited lengthened action potentials and reduced transient outward potassium current. TEB also increased reactive oxygen species (ROS) production in these cardiomyocytes, a phenomenon reversed by N-acetylcysteine (NAC). Furthermore, TEB-treated animals, when subjected to an in vivo dobutamine (Dob) and caffeine (Caf) challenge, displayed heightened susceptibility to severe arrhythmias, a phenotype prevented by NAC. In conclusion, TEB at the no observed adverse effect level (NOAEL) dose adversely affects heart electrical function, increases arrhythmic susceptibility, partially through ROS overproduction, and this phenotype is reversible by scavenging ROS with NAC.

Independent predictors of true positivity of positive myocardial perfusion imaging.

OBJECTIVE: The primary aim of the present study was to determine the success of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in detecting critical coronary artery disease (CAD) as identified by invasive coronary angiography (ICA), as well as to compare the positive predictive values (PPV) of different stress methods. Our secondary aim was to investigate demographic, laboratory, electrocardiographic, and echocardiographic variables that could predict true positive results. PATIENTS AND METHODS: The study was conducted with 317 consecutive patients. Exercise, dipyridamole, adenosine, or dobutamine were used as stress methods. According to the results of ICA, patients with and without critical CAD were divided into two groups and compared statistically. The independent predictors of true positive results of positive SPECT-MPI were determined using univariate and multivariate logistic regression analysis (MLRA). RESULTS: Among the patients, 129 (40.7%) were found to have critical CAD (+) and 188 (50.3%) critical CAD (-). The PPVs of different stress methods were similar. Age, diabetes, and monocyte to HDL ratio (MHR) were found to be independent predictors of critical CAD in MLRA (p<0.005, p=0.002, and p<0.005, respectively). ROC curve analysis revealed 81.4% sensitivity and 47.3% specificity (AUC: 0.683) at a cut-off of 57 for age and 72.1% sensitivity and 54.3% specificity (AUC: 0.649) for MHR at a cut-off of 9.7. CONCLUSIONS: The true positivity rate of SPECT-MPI is low. Moreover, this rate is much lower for women. The PPVs of different stress methods are similar. Age, presence of diabetes, and MHR ratio are independent predictors for true positive results of SPECT-MPI. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-9.jpg.

The epidemiology of postoperative dobutamine and phosphodiesterase inhibitors after adult elective cardiac surgery and its impact on the length of hospital stay: a post hoc analysis from the multicenter retrospective observational study.

The optimal administration of inotrope after cardiac surgery is unknown. This study aimed to investigate the impact of postoperative inotrope on clinical outcomes in adult elective cardiac surgery patients. Data from the Blood Pressure and Relative Optimal Target after Heart Surgery in Epidemiologic Registry study were analyzed, employing propensity score considering the hospital of admission. The primary outcome was the length of hospital stay evaluated using quantile regression. Secondary outcomes were kidney injury progression, renal replacement therapy, atrial fibrillation, mortality, mechanical ventilation duration, and length of intensive care unit (ICU) stay. Among 870 patients from 14 ICUs in Japan, 535 received inotropes within 24 h of ICU admission, with usage rates ranging from 40 to 100% among facilities. After propensity score matching, 218 patients were included in each group. The inotrope group had a significantly longer hospital stay compared to the control group (16 days vs. 14 days; median difference 1.78 [95% confidence interval [CI] 0.31-3.24]; p = 0.018). However, no significant differences were observed in the secondary outcomes, except for mechanical ventilation duration. The results of the sensitivity analysis using a mixed-effects quantile regression analysis considering the hospital of admission for length of hospital stay in the original cohort were consistent with the results of the propensity analyses (median difference in days, 2.35 [95% CI, 0.35-4.36]; p = 0.022). The use of inotropes within 24 h of ICU admission in adult elective cardiac surgery patients was associated with an extended hospitalization period of approximately 2 days, without offering any prognostic benefit. Clinical trial registration: UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm , UMIN000037074.

Survey on the Updated German S3 Guideline for Intensive Care in Cardiac Surgery Patients.

BACKGROUND: The German guideline on intensive care treatment of cardiac surgical patients provides evidence-based recommendations on management and monitoring. It remains unclear if, respectively, to which degree the guidelines are implemented into the daily practice. Therefore, this study aims to characterize the implementation of guideline recommendations in German cardiac surgical intensive care units (ICUs). METHODS: An internet-based online survey (42 questions, 9 topics) was sent to 158 German head physicians of cardiac surgical ICUs. To compare the effect over time, most questions were based on a previously performed survey (2013) after introduction of the last guideline update in 2008. RESULTS: A total of n = 65 (41.1%) questionnaires were included. Monitoring changed to increased provision of available transesophageal echocardiography specialists in 86% (2013: 72.6%), SvO2 measurement in 93.8% (2013: 55.1%), and electroencephalography in 58.5% (2013: 2.6%). The use of hydroxyethyl starch declined (9.4% vs. 2013: 38.7%), gelatin 4% presented the most administered colloid with 23.4% (2013: 17.4%). Low cardiac output syndrome was primarily treated with levosimendan (30.8%) and epinephrine (23.1%), while norepinephrine (44.6%) and dobutamine (16.9%) represented the most favored drug combination. The main way of distribution was web-based (50.9%), with increasing impact on therapy regimens (36.9% vs. 2013: 24%). CONCLUSION: Changes were found in all questioned sectors compared with the preceding survey, with persisting variability between ICUs. Recommendations of the updated guideline have increasingly entered clinical practice, with participants valuing the updated publication as clinically relevant.

Safety of dobutamine or adenosine stress cardiac magnetic resonance imaging in patients with left ventricular thrombus.

BACKGROUND: Left ventricular (LV) thrombus formation is a common but potentially serious complication, typically occurring after myocardial infarction. Due to perceived high thromboembolic risk and lack of safety data, stress cardiac magnetic resonance (CMR) imaging especially with dobutamine is usually avoided despite its high diagnostic yield. This study aimed to investigate the characteristics, safety and outcome of patients with LV thrombus undergoing dobutamine or vasodilator stress CMR. METHODS: Patients undergoing stress CMR with concomitant LV thrombus were retrospectively included. Risk factors, comorbidities, and previous embolic events were recorded. Periprocedural safety was assessed for up to 48 h following the examination. Major adverse cardiac events (MACE) 12 months before the diagnosis were compared to 12 months after the exam and between patients and a matched control group. Additionally, patients were followed up for all-cause mortality. RESULTS: 95 patients (78 male, 65 ± 10.7 years) were included. Among them, 43 patients underwent dobutamine (36 high-dose, 7 low-dose) and 52 vasodilator stress CMR. Periprocedural safety was excellent with no adverse events. During a period of 24 months, 27 MACE (14.7%) occurred in patients and controls with no statistical difference between groups. During a median follow-up of 33.7 months (IQR 37.6 months), 6 deaths (6.3%) occurred. Type of stress agent, thrombus mobility, or protrusion were not correlated to embolic events or death. CONCLUSION: The addition of a stress test to a CMR exam is safe and does increase the generally high cardioembolic event rate in LV thrombus patients. Therefore, it is useful to support reperfusion decision-making.

Anesthetic management of children with medically refractory pulmonary hypertension undergoing surgical Potts shunt.

INTRODUCTION: Pulmonary hypertension in children is associated with high rates of adverse events under anesthesia. In children who have failed medical therapy, a posttricuspid shunt such as a Potts shunt can offload the right ventricle and possibly delay or replace the need for lung transplantation. Intraoperative management of this procedure, during which an anastomosis between the pulmonary artery and the descending aorta is created, is complex and requires a deep understanding of the pathophysiology of acute and chronic right ventricular failure. This retrospective case review describes the intraoperative management of children undergoing surgical creation of a Potts shunt at a single center. METHODS: A retrospective case review of all patients under the age of 18 who underwent Potts shunt between April 2013 and June 2022. Medical records were examined, and clinical data of demographics, intraoperative vital signs, anesthetic management, and postoperative outcomes were extracted. RESULTS: Twenty-nine children with medically refractory pulmonary hypertension underwent surgical Potts shunts with a median age of 12 years (range 4 months to 17.4 years). Nineteen Potts shunts (65%) were placed via thoracotomy and 10 (35%) were placed via median sternotomy with use of cardiopulmonary bypass. Ketamine was the most frequently utilized induction agent (17 out of 29, 59%), and the majority of patients were initiated on vasopressin prior to intubation (20 out of 29, 69%). Additional inotropic support with epinephrine (45%), milrinone (28%), norepinephrine (17%), and dobutamine (14%) was used prior to shunt placement. Following opening of the Potts shunt, hemodynamic support was continued with vasopressin (66%), epinephrine (62%), milrinone (59%), dobutamine (14%), and norepinephrine (10%). Major intraoperative complications included severe hypoxemia (21 out of 29, 72%) and hypotension requiring boluses of epinephrine (10 out of 29, 34.5%) but no patient suffered intraoperative cardiac arrest. There were four in-hospital mortalities. DISCUSSION: A Potts shunt offers another palliative option for children with medically refractory pulmonary hypertension. General anesthesia in these children carries high risk for pulmonary hypertensive crises. Anesthesiologists must understand underlying physiological mechanisms responsble for acute hemodynaic decompensation during acute pulmonary hypertneisve crises. Severe physiological perturbations imposed by thoracic surgery and use of cardiopulmonay bypass can be mitigated by aggresive heodynamic support of ventricle function and maintainence of systemic vascular resistance. Early use of vasopressin, before or immidiately after anesthesia induction, in combination with other inotropes is a useful agent during the perioperative care of thes. Early use of vasopressin during anesthesia induction, and aggressive inotropic support of right ventricular function can help mitigate effects of induction and intubation, single-lung ventilation, and cardiopulmonary bypass. CONCLUSIONS: Our single center expereince shows that the Potts shunt surgery, despite high short-term mortaility, may offer another option for palliation in children with medically refractory pulmonary hypertension.

Dobutamine use in horses during romifidine and isoflurane anaesthesia.

This retrospective study aimed to assess the incidence of hypotension and the subsequent administration of dobutamine in horses anesthetized with isoflurane and romifidine during elective surgery. Time from induction of anaesthesia to administration of dobutamine was registered, as well as the time and dose needed to restore mean arterial pressure (MAP) ≥ 70 mmHg. Additionally, the influence of patient and anaesthesia related parameters on the need for dobutamine supplementation was evaluated. In total, 118 horses were included in this retrospective study. Dobutamine was administered to effect when MAP<70 mmHg. Data registered: patient weight, acepromazine premedication, body position, administration of intraoperative ketamine bolus, locoregional anaesthesia, mechanical ventilation, duration of anaesthesia, dose and duration of dobutamine administration, heart rate, MAP before dobutamine administration, MAP and time required to increase MAP≥70 mmHg. Dobutamine infusion was needed in 54.2% of the horses 30 ± 17 min after isoflurane-romifidine anaesthesia started. Dobutamine 0.55 ± 0.18 µg kg-1 min-1 achieved a MAP≥70 mmHg in 12 ± 8 min. Duration of dobutamine infusion was 56 ± 37 min. An univariable logistic regression showed a significant association between dobutamine and acepromazine administration (p = 0.01; OR = 3.43), anaesthesia time (p = 0.02; OR = 2.41) and dorsal recumbency (p < 0.001; OR = 8.40). In a multivariable logistic regression, only dorsal recumbency significantly increased the need for dobutamine supplementation (p < 0.001; OR = 7.70). There was no significant association between patient weight (p = 0.11; OR = 1), locoregional anaesthesia (p = 0.07; OR = 0.47), administration of a ketamine bolus (p = 0.95; OR = 0.98) or volume controlled ventilation (p = 0.94; OR = 1.04) and dobutamine administration. Low doses of dobutamine were suitable to restore MAP above 70 mmHg within a limited time period. Only dorsal recumbency increased the need of dobutamine administration.

[Prospective study on the influence of dobutamine on blood perfusion in free flap repair of diabetic foot wounds].

Objective: To investigate the influence of clinical administration of dobutamine on blood perfusion in free flap repair of diabetic foot wounds. Methods: A prospective self-controlled study was conducted. From January to November 2022, 20 patients with diabetic foot who met the inclusion criteria were hospitalized in the Department of Burns and Plastic Surgery of Affiliated Hospital of Zunyi Medical University, including 9 males and 11 females, aged from 44 to 75 years, with the foot wounds area ranging from 5 cm×4 cm to 20 cm×10 cm, which were repaired by free anterolateral thigh flaps. Heart rate (HR) and mean arterial pressure (MAP) were recorded before anesthesia induction, 10 minutes after vascular recanalization, when the target blood pressure (i.e., MAP being 6-10 mmHg (1 mmHg=0.133 kPa) higher than that before anesthesia induction) was reached after infusion of dobutamine, and 10 minutes after tracheal catheter removal. Additionally, indocyanine green, a contrast agent, was injected intravenously at 10 minutes after vascular recanalization and when the target blood pressure was reached after infusion of dobutamine to assess flap blood perfusion using infrared imager, and the area ratio of flaps with hyperperfusion and hypoperfusion was calculated. Other recorded variables included flap harvesting area, surgical duration, total fluid infusion amount, infusion dose and total usage of dobutamine, intraoperative adverse events, postoperative flap complications, and follow-up outcomes. Data were statistically analyzed with paired sample t test, analysis of variance for repeated measurement, Bonferroni method, and generalized estimating equation. Results: Compared with those before anesthesia induction, HR and MAP of patients were significantly decreased at 10 minutes after vascular recanalization (P<0.05), while HR and MAP of patients were significantly increased when the target blood pressure was reached after infusion of dobutamine (P<0.05). Compared with those at 10 minutes after vascular recanalization, HR and MAP of patients were significantly increased when the target blood pressure was reached after infusion of dobutamine and at 10 minutes after tracheal catheter removal (P<0.05). Compared with those when the target blood pressure was reached after infusion of dobutamine, HR and MAP of patients were significantly decreased at 10 minutes after tracheal catheter removal (P<0.05). The area ratio of flaps with hyperperfusion of patients was 0.63±0.11 when the target blood pressure was reached after infusion of dobutamine, which was significantly higher than 0.31±0.09 at 10 minutes after vascular recanalization (t=-9.92, P<0.05). The area ratio of flaps with hypoperfusion of patients was 0.12±0.05 when the target blood pressure was reached after infusion of dobutamine, which was significantly lower than 0.45±0.10 at 10 minutes after vascular recanalization (t=17.05, P<0.05). The flap harvesting area of patients was (174±35) cm², the surgical duration was (372±52) min, the total fluid infusion amount was (2 485±361) mL, the infusion dose of dobutamine was 3-13 µg·kg⁻¹·min⁻¹, and the total usage of dobutamine was 5.7 (2.1, 9.7) mg. Two patients showed a significant increase in MAP during the infusion of dobutamine compared with that at 10 minutes after vascular recanalization, but before reaching 6 mmHg higher than that before anesthesia induction, their HR had reached the maximum (over 130 beats/min). The HR gradually returned to around 90 beats/min after the infusion of dobutamine was stopped. On post operation day 2, one patient had partial necrosis at the distal part of the flap, which was repaired by transplantation of thin split-thickness skin graft from the opposite thigh. During the follow-up of 3 to 6 months after operation, all the flaps survived well, with soft texture and well-formed shape, and no adverse cardiovascular events of patients were reported. Conclusions: The administration of dobutamine in free flap repair of diabetic foot wounds can significantly improve the MAP of patients, expand the area of hyperperfusion, reduce the area of hypoperfusion, and enhance the flap viability, with promising short-term follow-up results, which is suitable for promotion in clinical applications.

Successful echocardiography-guided medical management of severe early post-implant right ventricular failure in a patient with left ventricular assist device support: a case report.

BACKGROUND: Post-implant right heart failure (RHF) has been recognized as a crucial prognostic factor in patients receiving left ventricular assist devices (LVADs), and its management has long attracted attention from cardiologists and surgeons. CASE PRESENTATION: This report described an 18-year-old female with acutely deteriorating heart failure due to dilated cardiomyopathy who underwent paracorporeal pulsatile-flow LVAD and developed early post-implant RHF. At postoperative day (POD) six, she was almost asymptomatic at rest on 2.5 mg/kg/min of dobutamine; however, the echocardiogram, performed as part of the daily postoperative care, revealed a severely enlarged right ventricle with a decompressed left ventricle, implying the development of post-implant RHF. Bolus infusion of saline and reduction of pump flow (6.0 L/min to 3.0 L/min) led to normalization of both ventricular shapes in 30 s, suggesting that RHF could be managed without surgical interventions. Milrinone was started on POD six, followed by sildenafil administration on POD seven. Fluid balance was strictly adjusted under the close observation of daily echocardiograms. Milrinone and dobutamine were discontinued on PODs 18 and 21, respectively. The patient was listed for a heart transplant on POD 40. Despite reduced right ventricular function (right ventricular stroke work index of 182.34 mmHg*ml/m- 2, body surface area 1.5 m2), she was successfully converted to implantable LVAD on POD 44 with no recurrence of post-implant RHF thereafter for four years. CONCLUSIONS: In post-implant RHF management, early detection, together with proper and prompt medical management, is crucial to avoiding any surgical intervention. Close observation of daily echocardiograms might be helpful in detecting subclinical RHF and is useful for post-implant medical management.

The choice of perioperative inotropic support impacts the outcome of small infants undergoing complex cardiac surgery: an observational study.

BACKGROUND: Vaso-inotropic agents are frequently used to prevent and/or treat low cardiac output syndrome in infants undergoing surgery for congenital heart disease. Due to the lack of comparative studies, their use is largely dependent on physician- and center preferences. The aim was to assess the impact of two different inotropic regimens, milrinone-epinephrine versus dobutamine on postoperative morbi-mortality in young children undergoing complex cardiac surgery. METHODS: All consecutive children younger than one year of age admitted for complex cardiac surgery (Risk Adjustment in Congenital Heart Surgery-1 [RACHS-1] score ≥3) with cardiopulmonary bypass (CPB) from January 2008 to December 2018 were included. Children received either milrinone in association with low dose epinephrine (milrinone-epinephrine group) or dobutamine (dobutamine group) groups were matched and compared using a propensity score. Our primary outcome was a composite measure including either hospital death and/or the presence of at least two of the following events: respiratory failure, prolonged inotropic support, or renal failure. RESULTS: Two hundred and fifty patients were included in the analysis. Children in the milrinone-epinephrine group (N.=184) suffered more frequently from a cyanotic heart disease and had longer surgery, CPB, and aortic cross clamp times than those in the dobutamine group (N.=66). After matching, children in the milrinone-epinephrine group had a higher incidence of severe postoperative morbidity or mortality compared to those in the dobutamine group (27.4 versus 13.9%; P=0.016). Respiratory failure (28% vs. 12%), prolonged inotropic support (71% vs. 35%) and in-hospital death (3 vs. 0%) were more frequent in the milrinone-epinephrine group. CONCLUSIONS: In young infants undergoing complex cardiac surgery, milrinone combined with epinephrine is associated with a higher incidence of postoperative morbidity or mortality compared to dobutamine for perioperative inotropic support. Further prospective randomized studies are required to confirm this finding.

Preoperative Levosimendan Administration in Heart Transplant Patients with Severe Hepatic and Renal Impairment: A Retrospective Study.

BACKGROUND: The cardio-renal syndrome and hepatic impairment play a critical role in end-stage heart failure (HF). Levosimendan is an effective inotropic agent used to maintain cardiac output similar to classic cardiotonic like dobutamine/dopamine. This current research aims to investigate the clinical outcomes of levosimendan and dobutamine/dopamine in Chinese heart transplant awaiting patients with severe hepatic or renal impairment. METHODS: We performed a retrospective analysis of 568 heart transplant awaiting individuals with severe hepatic or renal impairment who treated with levosimendan or dobutamine/dopamine in our institution between January 2015 and December 2020. Univariate Cox proportional hazard models and Kaplan-Meier survival curves were applied. The primary endpoint was defined as death included inhospital mortality and the mortality at 30 days, 90 days, 180 days and 1 year after heart transplantation. RESULTS: There were no significant differences in mortality rate at 30, 90, 180 days and 1 years after heart transplantation between the levosimendan and non-levosimendan groups, or between subgroups of patients with severe hepatic impairment or renal impairment. The results were consistent before and after propensity score matching. CONCLUSIONS: In the population with advanced heart failure awaiting heart transplantation, levosimendan did not increase short- or long-term mortality rates after surgery compared to dobutamine/dopamine, regardless of their hepatic or renal function. Severe hepatic or renal impairment were not necessarily considered a contraindication for levosimendan in these patients.

Protective Effects of Fuziline on Dobutamine-Induced Heart Damage in Mice.

INTRODUCTION: Fuziline is one of the many antioxidants currently being tested to treat cardiac damage. In our study, histopathological and biochemical effects of fuziline were investigated in mice with dobutamine-induced heart damage in vitro. METHODS: Thirty-two adult male BALB/c mice, average weight of 18-20 g, were randomly divided into four groups - Group 1 (sham, n=8), Group 2 (control, dobutamine, n=8), Group 3 (treatment 1, dobutamine + fuziline, n=8), and Group 4 (treatment 2, fuziline, n=8). Biochemical parameters and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were measured. Interleukin 1 beta (IL-1ß), NLR family, pyrin domain containing protein 3 (NLRP3), 8-hydroxy-deoxyguanosine (8-OHDG), gasdermin D (GSDMD), and galectin 3 (GAL-3) levels were analyzed by enzyme-linked immunosorbent assay method, and histopathological examination of heart tissues was performed. RESULTS: When dobutamine + fuziline and fuziline groups were compared, troponin-I (P<0.05), NLRP3 (P<0.001), GSDMD (P<0.001), 8-OHDG (P<0.001), IL-1ß (P<0.001), and GAL-3 (P<0.05) were found to be statistically significant. TOS level was the highest in the dobutamine group (P<0.001) and TAS level was the highest in the fuziline group (P<0.001). OSI level was statistically significant between the groups (P<0.001). In histopathological examination, focal necrosis areas were smaller in the dobutamine + fuziline group than in the dobutamine group, and cardiac myocytes were better preserved. CONCLUSION: Fuziline markedly reduced cardiac damage and pyroptosis in mice with dobutamine-induced heart damage by lowering the levels of GSDMD, 8-OHDG, IL-1ß, and GAL-3. It also prevented necrosis of cardiac myocytes in histopathological evaluation.

Characteristics, management, and outcomes of active cancer patients with cardiogenic shock.

AIMS: Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all aetiologies. METHODS AND RESULTS: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. 'Active cancer' was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72% vs. 52%, P = 0.005 and norepinephrine-dobutamine combination 64.7% vs. 44.5%, P = 0.005), but had less mechanical circulatory support (5.9% vs. 19.5%, P = 0.016). They presented a similar 30-day mortality rate (29% vs. 26%) but a significantly higher mortality at 1-year (70.6% vs. 45.2%, P < 0.001). In multivariable analysis, active cancer was not associated with 30-day mortality but was significantly associated with 1-year mortality in 30-day survivors [HR 3.61 (1.29-10.11), P = 0.015]. CONCLUSION: Active cancer patients accounted for almost 7% of all cases of cardiogenic shock. Early mortality was the same regardless of active cancer or not, whereas long-term mortality was significantly increased in patients with active cancer.

A knowledge graph-based analytical model for mining clinical value of drug stress echocardiography for diagnosis, risk stratification and prognostic evaluation of coronary artery disease.

The three major techniques for clinically diagnosing coronary heart disease, including angina associated with myocardial ischemia, are coronary angiography, myocardial perfusion imaging, and drug stress echocardiography. Compared to the first two methods, which are invasive or involve the use of radionuclides, drug stress echocardiography is increasingly used in clinical practice due to its non-invasive, low-risk, and controllable nature, and wide applicability. We developed a novel methodology to demonstrate knowledge graph-based efficacy analysis of drug stress echocardiography as a complement to traditional meta-analysis. By measuring coronary flow reserve (CFR), we discovered that regional ventricular wall abnormalities (RVWA) and drug-loaded cardiac ultrasound can be used to detect coronary artery disease. Additionally, drug-loaded cardiac ultrasound can be used to identify areas of cardiac ischemia, stratify risks, and determine prognosis. Furthermore, adenosine stress echocardiography(ASE) can determine atypical symptoms of coronary heart disease with associated cardiac events through CFR and related quantitative indices for risk stratification. Using a knowledge graph-based approach, we investigated the positive and negative effects of three drugs - Dipyridamole, Dobutamine, and Adenosine - for coronary artery disease analysis. Our findings show that Adenosine has the highest positive effect and the lowest negative effect among the three drugs. Due to its minimal and controlled side effects, and high sensitivity for diagnosing coronary microcirculation disorders and multiple lesions, adenosine is frequently used in clinical practice.

Efficacy of Co-Medications in Patients with Alcoholic Liver Disease.

BACKGROUND: Alcoholic liver disease (ALD) is still increasing and leads to acute liver injury but also liver cirrhosis and subsequent complications such as liver failure or hepatocellular carcinoma (HCC). As most patients fail to achieve alcohol abstinence, it is essential to identify alternative treatment options in order to improve the outcome of ALD patients. METHODS: Evaluating two large cohorts of patients with ALD from the USA and Korea with a total of 12,006 patients, we investigated the effect on survival of aspirin, metformin, metoprolol, dopamine, and dobutamine drugs in patients with ALD between 2000 and 2020. Patient data were obtained through the "The Observational Health Data Sciences and Informatics consortium," an open-source, multi-stakeholder, and interdisciplinary collaborative effort. RESULTS: The use of aspirin (p = 0.000, p = 0.000), metoprolol (p = 0.002, p = 0.000), and metformin (p = 0.000, p = 0.000) confers a survival benefit for both AUSOM- and NY-treated cohorts. Need of catecholamines dobutamine (p = 0.000, p = 0.000) and dopamine (p = 0.000, p = 0.000) was strongly indicative of poor survival. ß-Blocker treatment with metoprolol (p = 0.128, p = 0.196) or carvedilol (p = 0.520, p = 0.679) was not shown to be protective in any of the female subgroups. CONCLUSION: Overall, our data fill a large gap in long-term, real-world data on patients with ALD, confirming an impact of metformin, acetylsalicylic acid, and ß-blockers on ALD patient's survival. However, gender and ethnic background lead to diverse efficacy in those patients.

The effect of dobutamine treatment on salvage of digital replantation and revascularization.

PURPOSE: One of the most common causes of a failure after replantation and revascularization surgeries is 'no reflow' from proximal artery that occurs, especially following crush and avulsion injuries. In this study, we aimed to evaluate the effect of dobutamine treatment on salvage of replanted and revascularized digits. METHODS: The patients with no reflow phenomenon detected in the salvage operations of replanted/revascularized digits between the years 2017 and 2020 were included in the study. Dobutamine treatment was infused at a rate of 4 µg·kg-1·min-1 intraoperatively and of 2 µg·kg-1 min-1 postoperatively. Demographic data (age, sex), digit survival rate, ischemia time, and level of injury were retrospectively analysed. Pre-infusion, intraoperative and postoperative values of cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) were recorded. RESULTS: The phenomenon of 'no reflow' was encountered in 35 digits of 22 patients who underwent salvage surgery due to vascular compromise. The survival rate in the revascularization group was 75%, while it was 42.1% in the replanted digits. Metaphysis level of proximal phalanx was the most common localization for 'no reflow' phenomenon. The least values of CI, MAP and HR to obtain sufficient perfusion in salvaged digits were as follows: 4.2 l.min-1.m-2, 76 mm Hg, and 83 beat·min-1, respectively. CONCLUSIONS: It was demonstrated that dobutamine infusion at a rate of 4 µg·kg-1·min-1 intraoperatively and at 2 µg·kg-1·min-1 postoperatively has favorable effects on the vascular compromise derived from no reflow of proximal artery.

Stress granule activation attenuates lipopolysaccharide-induced cardiomyocyte dysfunction.

BACKGROUND: Sepsis is the leading cause of death in intensive care units. Sepsis-induced myocardial dysfunction, one of the most serious complications of sepsis, is associated with higher mortality rates. As the pathogenesis of sepsis-induced cardiomyopathy has not been fully elucidated, there is no specific therapeutic approach. Stress granules (SG) are cytoplasmic membrane-less compartments that form in response to cellular stress and play important roles in various cell signaling pathways. The role of SG in sepsis-induced myocardial dysfunction has not been determined. Therefore, this study aimed to determine the effects of SG activation in septic cardiomyocytes (CMs). METHODS: Neonatal CMs were treated with lipopolysaccharide (LPS). SG activation was visualized by immunofluorescence staining to detect the co-localization of GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and T cell-restricted intracellular antigen 1 (TIA-1). Eukaryotic translation initiation factor alpha (eIF2α) phosphorylation, an indicator of SG formation, was assessed by western blotting. Tumor necrosis factor alpha (TNF-α) production was assessed by PCR and enzyme-linked immunosorbent assays. CMs function was evaluated by intracellular cyclic adenosine monophosphate (cAMP) levels in response to dobutamine. Pharmacological inhibition (ISRIB), a G3BP1 CRISPR activation plasmid, and a G3BP1 KO plasmid were employed to modulate SG activation. The fluorescence intensity of JC-1 was used to evaluate mitochondrial membrane potential. RESULTS: LPS challenge in CMs induced SG activation and resulted in eIF2α phosphorylation, increased TNF-α production, and decreased intracellular cAMP in response to dobutamine. The pharmacological inhibition of SG (ISRIB) increased TNF-α expression and decreased intracellular cAMP levels in CMs treated with LPS. The overexpression of G3BP1 increased SG activation, attenuated the LPS-induced increase in TNF-α expression, and improved CMs contractility (as evidenced by increased intracellular cAMP). Furthermore, SG prevented LPS-induced mitochondrial membrane potential dissipation in CMs. CONCLUSION: SG formation plays a protective role in CMs function in sepsis and is a candidate therapeutic target.

Management and clinical outcomes of cardiogenic shock in King Abdulaziz University Hospital: A retrospective study.

OBJECTIVES: To assess frequencies of various management approaches in cardiogenic shock (CS) and their clinical outcomes. Cardiogenic shock is a state of organ hypoperfusion and hypoxia caused by cardiac failure. METHODS: In this retrospective record review, we assessed the presentations, vital signs, laboratory readings, and treatments for 188 consecutive CS inpatients from 2010-2021. Patients were labeled as "ischemic CS" or "non-ischemic CS" based on the occurrence of myocardial infarction as the precipitating cause, and "post-operative CS" if they had undergone cardiac surgery. In-hospital mortality was the primary endpoint of the study. RESULTS: We identified 118 (62.8%) ischemic, 64 (34%) non-ischemic, and 6 (3.2%) postoperative CS patients. The study population had a high mortality rate (85.1%). Logistic regression analysis revealed that dopamine (p=0.040) and epinephrine (p=0.001) were independent predictors of mortality, while dobutamine (p=0.004) and digoxin (p=0.044) associated with increased survival. No significant association with mortality was found between either PCI or IABP. No significant difference in mortality was observed between CS subgroups. CONCLUSION: Variations in outcomes occurred with different medications. Mortality was higher in patients receiving dopamine or epinephrine and lower in those receiving dobutamine or digoxin. Implementation of clinical trials for investigation of the mortality benefit observed with dobutamine can serve towards formulation of new guidelines for improvement of CS mortality rates.