Effects of ivabradine on the prevention of intradialytic hypotension in a dialytic patient with heart failure with reduced ejection fraction

A 65-year-old man with a history of heart failure with reduced ejection fraction (HFrEF) and renal failure was admitted due to difficulty in fluid volume control during haemodialysis. He had frequent episodes of intradialytic hypotension (IDH) with presyncope during haemodialysis despite using a vasopressor agent. Before haemodialysis, his blood pressure was 130–150/60–70 mm Hg, and his heart rate was 80–100 beats/min. There were no specific causes of IDH. For refractory IDH, he was treated with oral ivabradine (2.5 mg two times per day), which resulted in reduced heart rate and decreased occurrence of IDH. This is the first report to describe a dialysis case with HFrEF presenting with an elevated heart rate and impaired fluid management as manifested by recurring IDH, which improved after ivabradine treatment. Ivabradine therapy may assist in increasing stroke volume by lowering the sinus heart rate, thus resulting in the prevention of IDH.

Treatment With Vasopressor Agents for Cardiovascular Shock Patients With Poor Renal Function; Results From the Japanese Circulation Society Cardiovascular Shock Registry

According to the guidelines for cardiogenic shock, norepinephrine is associated with fewer arrhythmias than dopamine and may be the better first-line vasopressor agent. This study aimed to evaluate the utility of norepinephrine vs. dopamine as first-line vasopressor agent for cardiovascular shock depending on the presence and severity of renal dysfunction at hospitalization. This was a secondary analysis of the prospective, multicenter Japanese Circulation Society Cardiovascular Shock Registry (JCS Shock Registry) conducted between 2012 and 2014, which included patients with shock complicating emergency cardiovascular disease at hospital arrival. The analysis included 240 adult patients treated with norepinephrine alone (n = 98) or dopamine alone (n = 142) as the first-line vasopressor agent. Primary endpoint was mortality at 30 days after hospital arrival. The two groups had similar baseline characteristics, including estimated glomerular filtration rate (eGFR), and similar 30-day mortality rates. The analysis of the relationship between 30-day mortality rate after hospital arrival and vasopressor agent used in patients categorized according to the eGFR-based chronic kidney disease classification revealed that norepinephrine as the first-line vasopressor agent might be associated with better prognosis of cardiovascular shock in patients with mildly compromised renal function at admission (0.0 vs. 22.6%; P = 0.010) and that dopamine as the first-line vasopressor agent might be beneficial for cardiovascular shock in patients with severely compromised renal function [odds ratio; 0.22 (95% confidence interval 0.05–0.88; P = 0.032)]. Choice of first-line vasopressor agent should be based on renal function at hospital arrival for patients in cardiovascular shock.Clinical Trial Registration:http://www.umin.ac.jp/ctr/, Unique identifier: 000008441.

Abstract 429: First-Line Vasopressor Agent for Cardiogenic Shock Due to Acute Myocardial Infarction: Results From Tokyo CCU Network Registry

Background: In the guidelines for cardiogenic shock, norepinephrine, as compared with dopamine, was associated with fewer cases of arrhythmia and may be a better first-line vasopressor agent. However, few clinical studies have investigated the effects of optimal first-line vasopressor agents for patients with poor renal function. Methods: From a multicenter, prospective, cohort registry of emergency cardiovascular patients in Tokyo between 2013 and 2016, we identified adult patients with cardiogenic shock due to acute myocardial infarction (AMI) who received either norepinephrine, dopamine or both as a vasopressor agent without mechanical circulatory supports. Study patients were divided into 4 groups according to estimated glomerular filtration rate (eGFR). The primary endpoint was all-cause mortality at 30 days after admission. Results: Of the 4,034 patients with cardiogenic shock due to AMI, 665 were eligible for this study; 419 received norepinephrine (N group), 154 dopamine (D group), and 92 both agents (B group). There was a significant difference in the all-cause mortality rate between the three groups in the whole cohort (16.0% in the N group, 9.7% in the D group and 40.2% in the B group, P<0.001). In addition, there was a significant difference in the all-cause mortality rate between the three groups in the subgroups of patients with eGFR stage 3a and 3b. (Figure). After adjustment of independent factors for mortality, the odds ratio of the D group (reference, the N group) was 0.51 (95%CI 0.26-0.99, p=0.049). Conclusion: Compared with norepinephrine, dopamine was associated with a lower all-cause mortality rate for patients with cardiogenic shock due to AMI, especially patients with poor renal function.

Renal autoregulation in experimental septic shock and its response to vasopressin and norepinephrine administration

Evidence suggests that septic shock patients with chronic arterial hypertension may benefit from resuscitation targeted to achieve higher blood pressure values than other patients, possibly as a result of altered renal autoregulation. The effects of different vasopressor agents on renal autoregulation may be important in this context. We investigated the effects of arginine vasopressin (AVP) and norepinephrine (NE) on renal autoregulation in ovine septic shock. Sepsis was induced by fecal peritonitis. When shock developed (decrease in mean arterial pressure to <65 mmHg and no fluid responsiveness), animals were randomized to receive NE or AVP in a crossover design. Before the switch to the second vasopressor, the first vasopressor was discontinued for 30 min to ensure complete washout of the first vasopressor. Renal autoregulation was evaluated by recording the change in renal blood flow (RBF) in response to manual, stepwise reductions in renal inflow pressure. In this model, the lower limit of renal autoregulation was not significantly altered 6 h after sepsis induction (59 ± 9 vs. 64 ± 7 mmHg at baseline, P = 0.096). After development of shock, the autoregulatory threshold was lower with AVP than with NE (59 ± 5 vs. 65 ± 7 mmHg, P = 0.010). However, RBF was higher with NE both at the start of autoregulatory measurements (206 ± 58 vs. 170 ± 52 ml/min; P = 0.049) and at the autoregulatory threshold (191 ± 53 vs. 150 ± 47 ml/min; P = 0.008). As vasopressors may have different effects on renal autoregulation, blood pressure management in patients with septic shock should be individualized and take into account drug-specific effects. NEW & NOTEWORTHY Septic shock patients with chronic arterial hypertension may benefit from higher blood pressure targets due to underlying deficits in renal autoregulatory efficiency. The current study is the first to show that the choice of vasopressor agent can differentially affect renal autoregulation. These findings may contribute to more personalized blood pressure management in patients with septic shock.

Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery

Background Vasoplegic syndrome is a common complication after cardiac surgery and impacts negatively on patient outcomes. The objective of this study was to evaluate whether vasopressin is superior to norepinephrine in reducing postoperative complications in patients with vasoplegic syndrome. Methods This prospective, randomized, double-blind trial was conducted at the Heart Institute, University of Sao Paulo, Sao Paulo, Brazil, between January 2012 and March 2014. Patients with vasoplegic shock (defined as mean arterial pressure less than 65 mmHg resistant to fluid challenge and cardiac index greater than 2.2 l · min−2 · m−2) after cardiac surgery were randomized to receive vasopressin (0.01 to 0.06 U/min) or norepinephrine (10 to 60 μg/min) to maintain arterial pressure. The primary endpoint was a composite of mortality or severe complications (stroke, requirement for mechanical ventilation for longer than 48 h, deep sternal wound infection, reoperation, or acute renal failure) within 30 days. Results A total of 330 patients were randomized, and 300 were infused with one of the study drugs (vasopressin, 149; norepinephrine, 151). The primary outcome occurred in 32% of the vasopressin patients and in 49% of the norepinephrine patients (unadjusted hazard ratio, 0.55; 95% CI, 0.38 to 0.80; P = 0.0014). Regarding adverse events, the authors found a lower occurrence of atrial fibrillation in the vasopressin group (63.8% vs. 82.1%; P = 0.0004) and no difference between groups in the rates of digital ischemia, mesenteric ischemia, hyponatremia, and myocardial infarction. Conclusions The authors’ results suggest that vasopressin can be used as a first-line vasopressor agent in postcardiac surgery vasoplegic shock and improves clinical outcomes.

P139: Procedural sedation by advanced care paramedics for emergency GI endoscopy

Introduction: Acute upper gastrointestinal (UGI) bleeding is a relatively common emergency resulting in death in 6 to 8% of cases. UGI endoscopy is the intervention of choice which requires procedural sedation and analgesia (PSA). The Halifax Infirmary emergency department (ED) performs 1000 PSAs annually, performed by advanced care paramedics (ACPs). This has been shown safe for other indications for PSA, such as orthopedic procedures. Considering that UGI endoscopy involves upper airway manipulation, and patients are at an increased risk of massive bleeding, this procedure would be expected to be more complex and have an increased risk of adverse events (AEs). This study aims to compare PSA for UGI endoscopy performed by ACPs to that for orthopedic procedures for AEs, airway intervention and medication use. Methods: This study is a retrospective review of an ACP-performed ED PSA quality control database. A dataset was built matching 64 UGI endoscopy PSAs to 192 orthopedic PSAs by propensity scores calculated using age, gender and ASA classification. Outcomes assessed were hypotension (SBP < 100, or 15% decrease from baseline), hypoxia (SaO2 < 90), apnea (> 30sec), vomiting, arrhythmias and death in the ED. The need for airway intervention and medication use was assessed. Results: The UGI endoscopy group was 4.60 times more likely to suffer hypotension than the orthopedic group (OR=4.6, CI:2.2-9.6), and a fifth as likely to require airway repositioning (OR=0.2, CI:0.1-0.5). One endoscopy patient required endotracheal intubation. No patient died in either group. Compared to the orthopedic group, the UGI endoscopy group was one-third as likely to receive fentanyl (OR=0.3, CI:0.2-0.6). When fentanyl was administered, endoscopy patients received an average 26.7 mcg less than orthopedic patients. The endoscopy group was 15.4 times more likely to receive ketamine (OR=15.4, CI:4.7-66.5), and received 34.4 mg less on average. Four endoscopy patients received phenylephrine compared to none in the orthopedic group. There were no other differences. Conclusion: ED PSA for UGI endoscopy appears to differ significantly from that performed for orthopedic procedures. It was associated with more frequent hypotension and increased use of ketamine as a sedative. Patients undergoing UGI endoscopy were less likely to receive fentanyl and require airway repositioning. Only patients in the endoscopy group required intubation or a vasopressor agent.

Vasoconstrictor Responses to Vasopressor Agents in Human Pulmonary and Radial Arteries

Background: Vasopressor drugs, commonly used to treat systemic hypotension and maintain organ perfusion, may also induce regional vasoconstriction in specialized vascular beds such as the lung. An increase in pulmonary vascular tone may adversely affect patients with pulmonary hypertension or right heart failure. While sympathomimetics constrict pulmonary vessels, and vasopressin does not, a direct comparison between these drugs has not been made. This study investigated the effects of clinically used vasopressor agents on human isolated pulmonary and radial arteries. Methods: Isolated pulmonary and radial artery ring segments, mounted in organ baths, were used to study the contractile responses of each vasopressor agent. Concentration–response curves to norepinephrine, phenylephrine, metaraminol, and vasopressin were constructed. Results: The sympathomimetics norepinephrine, phenylephrine, and metaraminol caused concentration-dependent vasoconstriction in the radial (pEC50: 6.99 ± 0.06, 6.14 ± 0.09, and 5.56 ± 0.07, respectively, n = 4 to 5) and pulmonary arteries (pEC50: 6.86 ± 0.11, 5.94 ± 0.05 and 5.56 ± 0.09, respectively, n = 3 to 4). Vasopressin was a potent vasoconstrictor of the radial artery (pEC50 9.13 ± 0.20, n = 3), whereas in the pulmonary artery, it had no significant effect. Conclusions: Sympathomimetic-based vasopressor agents constrict both human radial and pulmonary arteries with similar potency in each. In contrast, vasopressin, although a potent vasoconstrictor of radial vessels, had no effect on pulmonary vascular tone. These findings provide some support for the use of vasopressin in patients with pulmonary hypertension.