Introduction: Angiotensin II may reduce muscle ischemia during intermittent hemodialysis and thereby decrease the incidence and/or intensity of intradialytic muscle cramps. We aimed to test whether angiotensin II infusion during intermittent hemodialysis is safe, feasible, and effective in the attenuation of muscle cramps.Methods: We performed a pilot, single-blinded, randomized crossover trial of patients receiving intermittent hemodialysis who frequently experience intradialytic muscle cramps. Patients were randomly allocated to receive either intravenous angiotensin II or placebo for the duration of their first dialysis session of the week. They crossed over to the alternate arm each week for four weeks. The primary outcome was safety. Secondary outcomes included cramp-related symptoms, hemodynamic parameters, dialysis prescription alterations, and biomarkers.Results: We studied 24 sessions in 6 patients. Intradialytic hypertension (systolic blood pressure >180mmHg) occurred more often with angiotensin II than with placebo (33% vs 17% sessions, P=0.64). There were no other adverse events. Compared with placebo, muscle cramps were less frequent (33% vs. 92% sessions, P=0.009) and of lower intensity with angiotensin II (median Brief Pain Inventory score 1.4 vs. 5.3; P<0.001; maximal Brief Pain Inventory score 1.2 vs. 6.0; P<0.001). Fluid bolus administration for cramps was less common during angiotensin II infusion than placebo (0% vs. 42% sessions, P=0.037).Conclusion: Angiotensin II increased blood pressure and heart rate but not cardiac output or levels of troponin, creatine kinase or renin. In conclusion, angiotensin II infusion during intermittent hemodialysis appears safe and effective at reducing intradialytic muscle cramps. These observations justify further investigation in larger controlled studies.

Introduction: Angiotensin II may reduce muscle ischemia during intermittent hemodialysis and thereby decrease the incidence and/or intensity of intradialytic muscle cramps. We aimed to test whether angiotensin II infusion during intermittent hemodialysis is safe, feasible, and effective in the attenuation of muscle cramps.Methods: We performed a pilot, single-blinded, randomized crossover trial of patients receiving intermittent hemodialysis who frequently experience intradialytic muscle cramps. Patients were randomly allocated to receive either intravenous angiotensin II or placebo for the duration of their first dialysis session of the week. They crossed over to the alternate arm each week for four weeks. The primary outcome was safety. Secondary outcomes included cramp-related symptoms, hemodynamic parameters, dialysis prescription alterations, and biomarkers.Results: We studied 24 sessions in 6 patients. Intradialytic hypertension (systolic blood pressure >180mmHg) occurred more often with angiotensin II than with placebo (33% vs 17% sessions, P=0.64). There were no other adverse events. Compared with placebo, muscle cramps were less frequent (33% vs. 92% sessions, P=0.009) and of lower intensity with angiotensin II (median Brief Pain Inventory score 1.4 vs. 5.3; P<0.001; maximal Brief Pain Inventory score 1.2 vs. 6.0; P<0.001). Fluid bolus administration for cramps was less common during angiotensin II infusion than placebo (0% vs. 42% sessions, P=0.037).Conclusion: Angiotensin II increased blood pressure and heart rate but not cardiac output or levels of troponin, creatine kinase or renin. In conclusion, angiotensin II infusion during intermittent hemodialysis appears safe and effective at reducing intradialytic muscle cramps. These observations justify further investigation in larger controlled studies.

Introduction: Hypotension is common during intermittent hemodialysis (IHD) and may be due to a decreased cardiac index (CI). However, no study has simultaneously and continuously measured CI and mean arterial pressure (MAP) to understand the prevalence, severity, and duration of CI decreases or relate them to MAP, blood volume (BV) and net ultrafiltration (NUF) rate.Methods: In a prospective, pilot and feasibility investigation, we studied 10 chronic IHD patients. We used the ClearSight System™ to continuously monitor CI and MAP; the CRIT-LINE®IV monitor to detect BV changes and collected data on NUF rate.Results: Device tolerance and compliance was 100%. All patients experienced at least ≥ 1 episode of severe CI decrease (> 25% from baseline), with a median duration of 24 minutes [IQR 6-87] and of 68 minutes [14-106] for moderate decreases (>15% but  25% from baseline). Eight patients experienced a low CI state (<2.2 L/min/m2). The lowest CI was 0.9 L/min/m2 with a concomitant MAP of 94 mmHg. When the fall in CI was severe, MAP increased in 58% of cases and remained stable in 28%. Overall, CI decreased by -0.55 L/min/m2 when BV decrease was moderate vs mild (p<0.001) and by -0.8 L/min/m2 when NUF rate was high vs low (p<0.001). Conclusion: Continuous CI monitoring is feasible in IHD and shows frequent moderate-severe CI decreases, sometimes to low CI state levels. Such decreases are typically associated with markers of decreased intravascular volume status but not with a decrease in MAP, implying marked vasoconstriction.

Introduction: Hypotension is common during intermittent hemodialysis (IHD) and may be due to a decreased cardiac index (CI). However, no study has simultaneously and continuously measured CI and mean arterial pressure (MAP) to understand the prevalence, severity, and duration of CI decreases or relate them to MAP, blood volume (BV) and net ultrafiltration (NUF) rate.Methods: In a prospective, pilot and feasibility investigation, we studied 10 chronic IHD patients. We used the ClearSight System™ to continuously monitor CI and MAP; the CRIT-LINE®IV monitor to detect BV changes and collected data on NUF rate.Results: Device tolerance and compliance was 100%. All patients experienced at least ≥ 1 episode of severe CI decrease (> 25% from baseline), with a median duration of 24 minutes [IQR 6-87] and of 68 minutes [14-106] for moderate decreases (>15% but  25% from baseline). Eight patients experienced a low CI state (<2.2 L/min/m2). The lowest CI was 0.9 L/min/m2 with a concomitant MAP of 94 mmHg. When the fall in CI was severe, MAP increased in 58% of cases and remained stable in 28%. Overall, CI decreased by -0.55 L/min/m2 when BV decrease was moderate vs mild (p<0.001) and by -0.8 L/min/m2 when NUF rate was high vs low (p<0.001). Conclusion: Continuous CI monitoring is feasible in IHD and shows frequent moderate-severe CI decreases, sometimes to low CI state levels. Such decreases are typically associated with markers of decreased intravascular volume status but not with a decrease in MAP, implying marked vasoconstriction.

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 01/01/2000 to 31/01/2023 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 3285 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 to 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). Discussion/Conclusion: There are limited data on CO changes during RRT. However, a decrease in CO appeared common and was marked in one of five patient cohorts. Such decreases often occurred without BP changes and were associated with increased SVR.

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 01/01/2000 to 31/01/2023 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 3285 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 to 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). Discussion/Conclusion: There are limited data on CO changes during RRT. However, a decrease in CO appeared common and was marked in one of five patient cohorts. Such decreases often occurred without BP changes and were associated with increased SVR.