A PILOT STUDY OF ANGIOTENSIN II AS PRIMARY VASOPRESSOR IN CRITICALLY ILL ADULTS WITH VASODILATORY HYPOTENSION: THE ARAMIS STUDY.

ABSTRACT: Objective: The aim of the study is to evaluate the efficacy and safety of using angiotensin II (Ang2) as primary vasopressor for vasodilatory hypotension. Methods: This was a prospective observational study of critically ill adults admitted to an academic intensive care unit (ICU) with vasodilatory hypotension. We treated 40 patients with Ang2 as primary vasopressor and compared them with 80 matched controls who received conventional vasopressors (norepinephrine, vasopressin, metaraminol, epinephrine, or combinations). Results : Mean age was 63 years and median Acute Physiology and Chronic Health Evaluation III score was 65. Ang2 patients had lower ICU mortality (10% vs 26%, P = 0.04); however, their 28- and 90-day mortality was not significantly different (18% vs 29%, P = 0.18; 22% vs 30%, P = 0.39). Peak serum creatinine levels were similar (128 vs 126 µmol/L, P = 0.81), as was the incidence and stage of acute kidney injury (70% vs 74%, P = 0.66), requirement for continuous renal replacement therapy (14% vs 13%, P = 0.84), and risk of major adverse kidney events at 7 days (20% vs 29%, P = 0.30). However, Ang2 patients with prior exposure to renin angiotensin aldosterone system inhibitors had a lower peak serum creatinine ( P = 0.03 for interaction) than conventional vasopressors patients, and serum troponin elevations were less common with Ang2 (8% vs 22%, P = 0.04). The incidence of thromboembolic complications was similar. Conclusions: Primary Ang2 administration in vasodilatory hypotension did not seem harmful compared with conventional vasopressors. Although Ang2 did not decrease peak serum creatinine levels or major adverse kidney events, its effects on intensive care unit survival, serum troponin, and renal function in patients on renin angiotensin aldosterone system inhibitors warrant further exploration in randomized trials (ACTRN12621000281897).

Modern Cardiac Surgical Outcomes in Nonagenarians: A Multicentre Retrospective Observational Study.

Background: There have been multiple recent advancements in the selection, optimisation and management of patients undergoing cardiac surgery. However, there is limited data regarding the outcomes in nonagenarians, despite this cohort being increasingly referred for these interventions. The objective of this study was to describe the patient characteristics, management and outcomes of a cohort of nonagenarians undergoing cardiac surgery receiving contemporary peri-operative care. Methods: After receiving ethics approval, we conducted a retrospective observational study of nonagenarians who had undergone cardiac surgery requiring a classic median sternotomy. All operative indications were included. We excluded patients who underwent transcatheter aortic valve implantation (TAVI), and surgery on the thoracic aorta via an endovascular approach (TEVAR). Patients undergoing TEVAR often have the procedure done under sedation and regional blocks with local anesthetic solution. There is no open incision and these patients do not require cardiopulmonary bypass. We also excluded patients undergoing minimally invasive mitral valve surgery via a videoscope assisted approach. These patients do not have a median sternotomy, have the procedure done via erector spinae block, and often are extubated on table. Data were collected from four hospitals in Victoria, Australia, over an 8-year period (January 2012-December 2019). The primary objective was to assess 6-month mortality in nonagenarian patients undergoing cardiac surgery and to provide a detailed overview of postoperative complications. We hypothesized that cardiac surgery in nonagenarian patients would be associated with a 6-month postoperative mortality <10%. As a secondary outcome, we hypothesized that significant postoperative complications (i.e., Clavien Dindo Grade IIIb or greater) would occur in > 30% of patients. Results: A total of 12,358 adult cardiac surgery patients underwent surgery during the study period, of whom 18 nonagenarians (0.15%) fulfilled inclusion criteria. The median (IQR) [min-max] age was 91.0 years (90.0:91.8) [90-94] and the median body mass index was 25.0 (kg/m2) (22.3:27.0). Comorbidities, polypharmacy, and frailty were common. The median predicted mortality as per EuroSCORE-II was 6.1% (4.1:14.5). There were no cases of intra-operative, in-hospital, or 6-month mortality. One (5.6%) patient experienced two Grade IIIa complications. Three (16.7%) patients experienced Grade IIIb complications. Three (16.7%) patients had an unplanned hospital readmission within 30 days of discharge. The median value for postoperative length of stay was 11.6 days (9.8:17.6). One patient was discharged home and all others were discharged to an inpatient rehabilitation facility. Conclusion: In this selected, contemporary cohort of nonagenarian patients undergoing cardiac surgery, postoperative 6-month mortality was zero. These findings support carefully selected nonagenarian patients being offered cardiac surgery (Trials Registry: https://www.anzctr.org.au/ACTRN12622000058774.aspx).

A pilot study of the pharmacokinetics of continuous magnesium infusion in critically ill patients.

Objective: The pharmacokinetics and haemodynamic effect of continuous magnesium infusion in non-cardiac intensive care unit (ICU) patients are poorly understood. We aimed to measure serum and urine magnesium levels during bolus and continuous infusion in critically ill adults, compare serum levels with those of a control population, and assess its haemodynamic effect. Design: Pharmacokinetic study Setting: A single tertiary adult ICU. Participants: Mechanically ventilated adults requiring vasopressor support. Intervention: A 10 mmol bolus of magnesium sulfate followed by 1.5-3 mmol/h infusion for 24 hours. Main outcome measures: The primary outcome was the change in total serum magnesium concentration. The main secondary outcome was mean arterial pressure (MAP)- adjusted vasopressor dose. Results: We matched 31 treated patients with 93 controls. Serum total magnesium concentration increased from a median 0.94 mmol/L (interquartile range [IQR], 0.83-1.10 mmol/L) to 1.38 mmol/L (IQR, 1.25-1.69 mmol/L; P < 0.001) and stabilised between a median 1.64 mmol/L (IQR, 1.38-1.88 mmol/L) at 7 hours and 1.77 mmol/L (IQR, 1.53-1.85 mmol/L) at 25 hours. This was significantly greater than in the control group (P < 0.001). The MAP-adjusted vasopressor dose decreased during magnesium infusion (P < 0.001). Conclusion: In critically ill patients, a magnesium sulfate bolus followed by continuous infusion achieved moderately elevated levels of total serum magnesium with a decrease in MAP-adjusted vasopressor dose. Trial registration number: ACTRN12619000925145.