Renin Levels and Angiotensin II Responsiveness in Vasopressor-Dependent Hypotension.

OBJECTIVES: The relationship between renin levels, exposure to renin-angiotensin system (RAS) inhibitors, angiotensin II (ANGII) responsiveness, and outcome in patients with vasopressor-dependent vasodilatory hypotension is unknown. DESIGN: We conducted a single-center prospective observational study to explore whether recent RAS inhibitor exposure affected baseline renin levels, whether baseline renin levels predicted ANGII responsiveness, and whether renin levels at 24 hours were associated with clinical outcomes. SETTING: An academic ICU in Melbourne, VIC, Australia. PATIENTS: Forty critically ill adults who received ANGII as the primary agent for vasopressor-dependent vasodilatory hypotension who were included in the Acute Renal effects of Angiotensin II Management in Shock study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After multivariable adjustment, recent exposure to a RAS inhibitor was independently associated with a relative increase in baseline renin levels by 198% (95% CI, 36-552%). The peak amount of ANGII required to achieve target mean arterial pressure was independently associated with baseline renin level (increase by 46% per ten-fold increase; 95% CI, 8-98%). Higher renin levels at 24 hours after ANGII initiation were independently associated with fewer days alive and free of continuous renal replacement therapy (CRRT) (-7 d per ten-fold increase; 95% CI, -12 to -1). CONCLUSIONS: In patients with vasopressor-dependent vasodilatory hypotension, recent RAS inhibitor exposure was associated with higher baseline renin levels. Such higher renin levels were then associated with decreased ANGII responsiveness. Higher renin levels at 24 hours despite ANGII infusion were associated with fewer days alive and CRRT-free. These preliminary findings emphasize the importance of the RAS and the role of renin as a biomarker in patients with vasopressor-dependent vasodilatory hypotension.

Carboxyhemoglobin in Cardiac Surgery Patients and Its Association with Risk Factors and Biomarkers of Hemolysis.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with hemolysis. Yet, there is no easily available and frequently measured marker to monitor this hemolysis. However, carboxyhemoglobin (CO-Hb), formed by the binding of carbon monoxide (a product of heme breakdown) to hemoglobin, may reflect such hemolysis. We hypothesized that CO-Hb might increase after cardiac surgery and show associations with operative risk factors and indirect markers for hemolysis. METHODS: We conducted a retrospective descriptive cohort study of data from on-pump cardiac surgery patients. We analyzed temporal changes in CO-Hb levels and applied a generalized linear model to assess patient characteristics associated with peak CO-Hb levels. Additionally, we examined their relationship with red blood cell (RBC) transfusion and bilirubin levels. RESULTS: We studied 38,487 CO-Hb measurements in 1735 patients. CO-Hb levels increased significantly after cardiac surgery, reaching a peak CO-Hb level 2.1 times higher than baseline (P < .001) at a median of 17 hours after the initiation of surgery. Several factors were independently associated with higher peak CO-Hb, including age (P < .001), preoperative respiratory disease (P = .001), New York Heart Association Class IV (P = .019), the number of packed RBC transfused (P < .001), and the duration of CPB (P = .002). Peak CO-Hb levels also significantly correlated with postoperative total bilirubin levels (Rho = 0.27, P < .001). CONCLUSIONS: CO-Hb may represent a readily obtainable and frequently measured biomarker that has a moderate association with known biomarkers of and risk factors for hemolysis in on-pump cardiac surgery patients. These findings have potential clinical implications and warrant further investigation.

The Impact of Early Positive Studies on the Evolution of Extracorporeal Albumin Dialysis Literature: A Bibliometric Analysis.

INTRODUCTION: Liver failure is a life-threatening condition characterized by the accumulation of metabolic toxins. Extracorporeal albumin dialysis (ECAD) has been promoted as a possible therapy. METHODS: We employed bibliometric analysis to scrutinize the conceptual, intellectual, and social structure of the ECAD literature including its co-citation network and thematic analysis to explore its evolution and organization. RESULTS: We identified 784 documents with a mean of 30.25 citations per document in a corpus of 15,191 references. The average citation rate peaked in 1998 at 280.75 citations/year before a second 2013 peak of 54.81 citations/year and then progressively decreased to its nadir in 2022 (1.48 yearly citations). We identified four primary co-citation clusters, with the most impactful publications being small "positive" manuscripts by Mitzner et al. (2000) and Heemann et al. (2002) (Cluster 1). This first cluster had several relational citations with clusters 2 and 3, but almost no citation link with cluster 4 represented by Bañares et al. (2013), Saliba et al. (2013), and Larsen et al. (2016), with their three negative randomized controlled trials. Finally, the thematic map revealed a shift in focus over time, with inflammation and ammonia as recent emergent themes. CONCLUSIONS: This bibliometric analysis provided a transparent and reproducible longitudinal assessment of ECAD literature and demonstrated how positive studies with low levels of evidence can dominate a research field and overshadow negative findings from higher quality studies. These insights hold significant implications for future research and clinical practice within this domain.

Renal medullary oxygenation during laparoscopic vs open surgery: the impact of blood pressure management-a pilot randomized controlled trial.

The impact of blood pressure targets and surgical approach (laparoscopic or open) on continuous urinary oxygenation (PuO2), a validated surrogate of renal medullary PO2, during general surgery, is unclear. We aimed to assess the effects of different blood pressure targets and surgical procedures on PuO2. We randomized patients receiving either laparoscopic or open surgery into two mean arterial pressure (MAP) target groups: usual MAP or a high MAP. We measured PuO2 in real-time and analyzed it according to the type of surgery and blood pressure target. The study was retrospectively registered on the 5th of July 2023 (ACTRN12623000726651). We included 43 participants who underwent either laparoscopic (n = 20) or open surgery (n = 23). We found that PuO2 significantly decreased during both laparoscopic and open surgery under a usual blood pressure target (- 51% and - 49%, respectively). However, there was a sharper fall with laparoscopic surgery resulting in a higher PuO2 with open surgery (mean difference: 11 ± 1 mmHg higher; p < 0.001). Targeting a higher MAP resulted in a higher PuO2 over time during laparoscopic surgery (mean difference: 7 ± 1 mmHg, p < 0.001). In contrast, targeting a usual MAP resulted in a higher PuO2 during open surgery (mean difference: 7 ± 1 mmHg, p < 0.001). Surgical approach and intraoperative blood pressure targets significantly impact urinary oxygenation. Further studies with larger sample sizes are needed to confirm these findings and understand their potential clinical implications.Registration number: ACTRN12623000726651; Date of registration: 05/07/2023 (retrospectively registered).

Cardiac Output Changes during Renal Replacement Therapy: A Scoping Review.

INTRODUCTION: Renal replacement therapy (RRT) is associated with hypotension. However, its impact on cardiac output (CO) is less understood. We aimed to describe current knowledge of CO monitoring and changes during RRT. METHODS: We searched MEDLINE, Embase, and Cochrane from January 1, 2000, to January 31, 2023, using Covidence for studies of intermittent hemodialysis (IHD) and continuous RRT (CRRT) with at least three CO measurements during treatment. Two independent reviewers screened citations, and a third resolved disagreements. The findings did not allow meta-analysis and are presented descriptively. RESULTS: We screened 3,285 articles and included 48 (37 during IHD, nine during CRRT, and two during both). Non-invasive devices (electrical conductivity techniques and finger cuff pulse contour) were the most common CO measurement techniques (21 studies). The median baseline cardiac index in IHD studies was 3 L/min/m2 (95% CI, 2.7-3.39). Among the 88 patient cohorts studied, a decrease in CO occurred in 63 (72%). In 16 cohorts, the decrease was severe (>25%). Changes in blood pressure (BP) were not concordant in extent or direction with changes in CO. The decrease in CO correlated weakly with ultrafiltration rate (r = -0.3, p = 0.05) and strongly with changes in systemic vascular resistance (SVR) (r = -0.6, p < 0.001). CONCLUSION: There are limited data on CO changes during RRT. However, a decrease in CO appeared common and was marked in 1 of 5 patient cohorts. Such decreases often occurred without BP changes and were associated with increased SVR.

Exploring the norepinephrine to angiotensin II conversion ratio in patients with vasodilatory hypotension: A post-hoc analysis of the ARAMIS trial.

PURPOSE: Angiotensin II is approved for catecholamine-refractory vasodilatory shock but the conversion dose ratio from norepinephrine to angiotensin II remains unclear. METHODS: We conducted a post-hoc analysis of the Acute Renal effects of Angiotensin II Management in Shock (ARAMIS) trial involving patients with vasodilatory hypotension. We determined the norepinephrine equivalent dose immediately prior to angiotensin II initiation and calculated the conversion dose ratio between norepinephrine and angiotensin II. We performed subgroup analyses based on recent exposure to angiotensin receptor blockers (ARBs) and renin levels at baseline. RESULTS: In 37 patients, the median conversion dose ratio between norepinephrine equivalent and angiotensin II was to 10:1 for norepinephrine bitartrate (5:1 for norepinephrine base). The conversion ratio was not affected by the baseline renin, with a median ratio of 10 (7-21) in the high renin group versus 12 (5-22) in the low renin group. Finally, exposure to ARBs prior admission appeared to diminish the conversion ratio with a median ratio of 7 (4-13) in ARB patients vs. 12 (7-22) in non-ARB patients. CONCLUSIONS: The norepinephrine to angiotensin II conversion dose ratio is 10:1 in a vasodilatory hypotension population. These findings can guide clinicians and researchers in the use, dosing, and study of angiotensin II in critical care.

Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial.

BACKGROUND: Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. METHODS: We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score. RESULTS: We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520-2593) ml with placebo and 2948 (2181-3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [- 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes. CONCLUSION: In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020.

Kinetics of the Cell Cycle Arrest Biomarkers (TIMP2 and IGFBP7) for the Diagnosis of Acute Kidney Injury in Critically Ill COVID-19 Patients.

BACKGROUND: Acute kidney injury (AKI) is highly prevalent in critical COVID-19 patients. The diagnosis and staging of AKI are based on serum creatinine (sCr) and urinary output criteria, with limitations in the functional markers. New cell-cycle arrest biomarkers [TIMP2]*[IGFBP7] have been proposed for early detection of AKI, but their role in critically ill COVID-19 patients is poorly understood. METHODS: We conducted an observational study to assess the performance of [TIMP2]*[IGFBP7] for the detection of AKI in critical COVID-19 patients admitted to our intensive care unit (ICU). We sampled urinary [TIMP2]*[IGFBP7] levels at ICU admission, 12 h, 24 h, and 48 h, and compared the results to the development of AKI, as well as baseline and laboratory data. RESULTS: Forty-one patients were enrolled. The median age was 66 years [57-72] and most were males (85%). Thirteen patients (31.7%) developed no/mild stage AKI, 19 patients (46.3%) moderate AKI, and nine patients (22.0%) severe AKI. The ICU mortality was 29.3%. sCr levels in the Emergency Department or at ICU admission were not significantly different according to AKI stage. [TIMP-2]*[IGFBP-7] urinary levels were elevated in severe AKI at 12 h after ICU admission, but not at ICU admission or 24 h or 48 h after ICU admission. CONCLUSION: Urinary biomarkers [TIMP-2]*[IGFBP-7] were generally increased in this population with a high prevalence of AKI, and were higher in patients with severe AKI measured at 12 h from ICU admission. Further studies are needed to evaluate the best timing of these biomarkers in this population.

The Cardiac Power Index during Abdominal Open Aortic Surgery: Intraoperative Insights into the Cardiac Performance-A Retrospective Observational Analysis.

Background: The Cardiac Power Index (CPI) measures the rate of energy output generated by the heart and correlates this with in-hospital mortality due to cardiogenic shock. In open aortic surgery, both aortic clamping and unclamping expose the heart to abrupt variations of the left ventricle afterload, preload, and contractility, with possible hemodynamic impairment. We investigated how aortic-cross clamping (Ao-XC) and unclamping (Ao-UC) procedures affect the CPI during open aortic surgery. Methods: We retrospectively analyzed our surgical database of 67 patients submitted to open surgical aortic repair at Humanitas Research Hospital, Milan. Patients were monitored by an EV1000-FloTrac SystemTM (Edwards Lifescience, Irvine, CA, USA) beyond the standard intra-operative hemodynamic monitoring. The primary outcome was the variation of basal CPI after aortic clamping and unclamping. Secondary outcomes were variations of the cardiac index (CI), mean arterial pressure (MAP), heart rate, and lactate during aortic clamping and after unclamping. The CPI was computed as: (CI × MAP)/451. Results: The CPI changed significantly after aortic unclamping. CPI: basal = 0.39 ± 0.1 W/m2, after Ao-XC = 0.39 ± 0.1 W/m2, and after Ao-UC = 0.44 ± 0.2 W/m2, p < 0.05. The CI changed during both cross-clamping and unclamping (p < 0.0001), whilst the MAP and heart rate did not during any phase of the surgery. Five subjects (8.3%) needed inotropic support after cross-clamping. Their basal CPI was lower than the general population: 0.31 ± 0.11 W/m2 vs. 0.39 ± 0.1 W/m2. Conclusions: The CPI describes the adaptation of the cardiac function to the changes in preload, contractility, and afterload occurring during aortic cross-clamping and unclamping. It may be used to explore the cardiac performance in real-time and predict cardiac impairment in the intraoperative period in a minimally invasive way, similar to ventriculo-arterial coupling parameters.

Barotrauma in mechanically ventilated patients with Coronavirus disease 2019: a survey of 38 hospitals in Lombardy, Italy.

BACKGROUND: The aim was to describe the incidence and risk factors of barotrauma in patients with the Coronavirus disease 2019 (COVID-19) on invasive mechanical ventilation, during the outbreak in our region (Lombardy, Italy). METHODS: The study was an electronic survey open from March 27th to May 2nd, 2020. Patients with COVID-19 who developed barotrauma while on invasive mechanical ventilation from 61 hospitals of the COVID-19 Lombardy Intensive Care Unit network were involved. RESULTS: The response rate was 38/61 (62%). The incidence of barotrauma was 145/2041 (7.1%; 95%-CI: 6.1-8.3%). Only a few cases occurred with ventilatory settings that may be considered non-protective such as a plateau airway pressure >35 cmH2O (2/113 [2%]), a driving airway pressure >15 cmH2O (30/113 [27%]), or a tidal volume >8 mL/kg of ideal body weight and a plateau airway pressure >30 cmH2O (12/134 [9%]). CONCLUSIONS: Within the limits of a survey, patients with COVID-19 might be at high risk for barotrauma during invasive (and allegedly lung-protective) mechanical ventilation.