Cardio-Thoracic Ratio 0.6 0.58 *P =0.026 RATIO 0.56 0.54 0.52 0.5 Month-0 Month-2 LUS Clinical *Adjusted with baseline CT ratio (Month 0) Groups Month-0 Month-2 LUS 0.57 0.557 0.531 Clinical 0.538 Mean difference *0.019 P-value *0.026
Complications Variables US Clinical P-value Hypertension, mean ± SD 0.046 ± 0.096 0.075 ± 0.119 0.41 0.19 Hypotension, mean 0.078 ± 0.123 0.141 ± 0.170 ± SD 0.60 0.052 ± 0.065 0.074 ± 0.175 0.47 Muscle cramp, 0.006 ± 0.025 0.011 ± 0.024 mean ± SD Other, mean ± SD ✓Incidences of intradialytic complications were similar in both groups ✓Closer levels of optimal dry weight obtained by BIAs, than the clinical group
Limitation • Low population→ Ongoing study Conclusion • LUS was helpful in volume assessment and fluid-guided management to achieve dry weight and control blood pressure • Further larger clinical trials should be conducted to prove benefit in survival of HD patients
•. 2021 Dec;100(6):1325-1333. LUST Trial Kidney Int. 2021 Dec;100(6):1325-1333.
LUNG ULTRASOUND-GUIDED TREATMENT FOR HEART FAILURE: AN UPDATED META-ANALYSIS AND TRIAL SEQUENTIAL ANALYSIS • The current pooled evidence indicates beneficial effect of LUS-guided therapy on MACEs, HF-related rehospitalization, and symptomatic HF compared with usual care. • However, the sample size was still small, and there is insufficient evidence to reach definitive conclusion on the effectiveness of LUS-guided treatment in the management of HF. Front. Cardiovasc. Med., 22 August 2022
Lifestyle Modification and Achieve Dry Weight Hypotension ↑Serum ↑Dialysate • Restrict Na and fluid intake with Na Na • Low dialysate Na down to 135 Saline tx Chronic mEq/L Volume ↑Thirst Non- Overload • Dry weight reduction: optimal 0.2kg/session-0.1kg/10kg/session Dry weight ↑Water Tool guided mx: BVM, BCM, LUS Intake • Prolong/Slow UF dialysis to achieve Dry Wt: > 4-12 weeks, add time/wk Am J Kidney Dis. 2015;66(5):884-930 KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients
Hypertension W/U 2nd Causes Management Algorithm KDOQI 2005 in Dialysis Patients Guidelines for Cardiovascular Disease in Dialysis Patients
Anti-hypertensive Drugs in Chronic Hemodialysis
Guideline for Selection: Anti-HT Drug Therapy in Dialysis KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients
Guideline for Selection: Anti-HT Drug Therapy in Dialysis Calcium channel blockers and alpha blockers can be added on to achieve BP control if necessary KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients
Non-dippers in Chronic Hemodialysis HD patients loss of natural diurnal BP • Antihypertensive drugs should be variation, called as non-dipper→ given preferentially at night • To reduce the nocturnal surge of morning surge hypertension blood pressure • And to minimize intradialytic hypotension … which may occur when drugs are taken the morning before a dialysis session (C) Comprehensive Clinical Nephrology 6th ed KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients
RAAS Blockade: ACEIs/ARBs • RCT: trends were observed suggesting fosinopril may be associated with lower risk of CVEs as compared with placebo in patients on HD with left ventricular hypertrophy • RCT: Inconsistent results related to ARBs and cardiovascular outcomes • Meta-analysis: ACEis/ARBs may reduce left ventricular mass index • RCT: May preserve residual kidney function, especially in PD patients JE Flythe et al. Kidney International (2020) 97, 861–876
Fosinopril in Dialysis (FOSIDIAL) Study • 397 patients were randomized to fosinopril 5 mg titrated to 20 mg daily (n=196) or placebo(n=201) plus conventional therapy for 24 months • The primary end point was combined fatal and nonfatal first major CVEs (cardiovascular death, resuscitated death,nonfatal stroke, heart failure, myocardial infarction, orrevascularization) • Trends were observed suggesting fosinopril may be associated with lower risk of CVEs • These trends may have become statistically significant had the sample size been larger Kidney International 2006;70:1318-1324
ACEis in Chronic Hemodialysis Drugs Dosage Excretion Removal with HD Supplement for HD Captopril 6.25–25 mg t.i.d. K 50% Enalapril 2.5–5 mg q 12 h K (L) 50% 12.5–25 mg Lisinopril 50% 2.5–5 mg Ramipril 5 mg q.d. K 20% 2.5–5 mg Fosinopril 5 mg q.d. K (L) None 2.5 mg 5-10 mg q.d. K (L) None NW Levin et al. Kidney International 2009
ARBs in Chronic Hemodialysis Drugs Dosage Excretion Removal with HD Supplement for HD Irbesartan 75–300 mg/day L None None Losartan 50–100 mg q.d. K (L) None None Telmisartan 40–80 mg/day None None Candesartan 8–35 mg/day L None None Valsartan 80–320 mg q.d. K (L) None None L (K) NW Levin et al. Kidney International 2009
Diuretics • Prospective: May help preserve residual diuresis and limit fluid overload • Prospective: Minimal effect on central hemodynamic indices and should not be considered an antihypertensive medication in the setting of dialysis • Observational: Continuation of loop diuretics after HD initiation is associated with lower IDWG and lower intradialytic hypotension and hospitalization rates Kidney Int. 2001;59:1128–1133. Clin Exp Nephrol. 2011;15:554–559. Nephrol Dial Transplant. 2008;23:1355–1361. Clin J Am Soc Nephrol. 2019;14:95–102.
Mineralocorticoid receptor antagonists • RCT: Some trials in patients on dialysis have shown benefit on cardiovascular outcomes with spironolactone vs. placebo,whereas others have not • Ongoing RCTs: spironolactone and cardiovascular outcomes in HD patients (ACHIEVE and ALCHEMIST) J Am Coll Cardiol. 2014;63:528–536. J Clin Hypertens (Greenwich). 2016;18:121–128. J Am Soc Nephrol. 2014;25:1094–1102. Kidney Int. 2019;95:983–991. Kidney Int. 2019;95:747–749.
Hypertension W/U 2nd Causes Management Algorithm in Dialysis Patients Reassess KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients
Intradialytic Blood Pressure Behavior
Patterns of Intradialytic BP Behavior Flythe et al. Am J Nephrol 2015;42:337–350
Association of Blood Pressure Increases During Hemodialysis With 2-Year Mortality in Incident Hemodialysis Patients • prospective cohort of 1,748 incident dialysis patients in USA • enrolled in the Dialysis Morbidity and Mortality Study (DMMS) Wave 2 • Every 10 mm Hg rise in pre- to post-HD systolic BP was associated with 12% ↑ in mortality risk Inrig et al. Am J Kidney Dis. 2009 November ; 54(5): 881–890.
Association of Nadir Intradialytic SBP with all-cause mortality • after adjustment for case-mix covariates, niSBP exhibited U-shaped association with 5-year all-cause mortality where patients with both higher (>140 mmHg) and lower (<90 mmHg) niSBP had mortality HRs of 1.43 (1.35–1.52) and 1.73 (1.63–1.84) Nephrol Dial Transplant. 2018 Jan 1;33(1):149-159.
Association of change in intradialytic BP with mortality • Using reference group of ΔiSBP 20 to ≤30 mmHg, patients with <15 mmHg drop had HR of 1.31 (1.26–1.37) and patients with ≥50 mmHg drop had HR of 1.32 (1.24–1.39). Nephrol Dial Transplant. 2018 Jan 1;33(1):149-159.
Association of Intradialytic BP Variability with Increased All-Cause and Cardiovascular Mortality in Long-term HD • Retrospective all-cause mortality cardiovascular mortality observational cohort • 6,393 thrice- weekly HD patients • from 1,026 dialysis units in USA • High SBP variability (>8.7 mmHg) was associated with greater risk of all-cause mortality (adjusted HR, 1.26; 95% CI, 1.08-1.47) • and cardiovascular mortality was even more potent (adjusted HR, 1.32; 95% CI, 1.01-1.72). Flythe et al. Am J Kidney Dis. 2013;61(6):966-974
Intradialytic Hypertension
Hypertension. 2022;79:855–862
Pathophysiology of Intradialytic Hypertension Flythe et al. Am J Nephrol 2015;42:337–350
Definition • No standard definition of • ↑ SBP > 15 mmHg within or immediately post- Intradialytic dialysis Hypertension • ↑ SBP >10 mmHg from pre to post-dialysis • ↑ BP of any degree during 2nd–3rd hour of hemodialysis • ↑ in BP that is resistant to ultrafiltration • ↑ SBP >10 mmHg from pre- to post-dialysis in the hypertensive range in at least 4 of 6 consecutive dialysis treatments • should prompt more extensive evaluation of BP and volume management, including home and/or ABPM • KDIGO 2020, BP and volume control in dialysis: a conference report Am J Kidney Dis. 2010 March ; 55(3): 580–589 JE Flythe et al. Kidney International (2020) 97, 861–876
Effect of Low Versus High Dialysate Sodium on BP and Endothelial- Derived Vasoregulators During Hemodialysis (MATCH-NA study) • 3-week, 2-arm, randomized, crossover study, 16 pts with intradialytic hypertension. • Intervention: Low (5 mEq/L below serum sodium) versus high (5 mEq/L above serum sodium) dialysate sodium • Outcomes: Endothelin 1, nitrite (NO2 2), and BP • Low dialysate sodium concentrations significantly decreased systolic BP and ameliorated intradialytic hypertension Jula K. Inrig et al, Am J Kidney Dis. 2015;65(3):464-473
Requires Intervention: • When Systolic blood pressure is greater than 180 mm Hg • Best are : • Clonidine • Central-acting ,alpha2 agonist • Symphatholytic agent (reduce HR, PVR, BP, renal vascular resistence ) • Onset <1hr , peak 2-4hr, half life 12hr • Short-acting ACE inhibitor such as Captopril • Practice: Hydralazine, beware of reflex tachycardia • The use of vasodilator drugs (hydralazine, minoxidil) • can lead to increased fluid retention that worsens volume overload • Minoxidil also can cause pleural and pericardial effusions and should be avoided in dialysis patients if at all possible Comprehensive Clinical Nephrology 6th ed
Tension in Balancing Volume Status within a Narrow Therapeutic Window
Intradialytic Hypotension
Proportion of intradialytic hypotension with mortality • Incremental association between higher proportion of IDH with mortality outcomes. Patients with >40% proportion of IDH had HR of 1.65 (1.57–1.73) higher mortality risk Nephrol Dial Transplant. 2018 Jan 1;33(1):149-159.
Association of Nadir Intradialytic SBP with all-cause mortality • compared with patients with niSBP of 110 to <120 mmHg, patients with baseline mean niSBP <90 mmHg had 5-year mortality hazard ratio (HR) [95% CI] of 3.14 (2.98–3.31), while patients with a mean niSBP >120 mmHg demonstrated survival benefit Nephrol Dial Transplant. 2018 Jan 1;33(1):149-159.
Definition KDOQI 2005 Guidelines11 of • Decrease in SBP ≥ 20 mm Hg Intradialytic or mean BP ≥ 10 mm Hg Hypotension • with associated symptoms (cramping, headache, lightheadedness, vomiting, or chest pain) • Or need for intervention (reduction in UF or administration of fluids) JE Flythe et al. Kidney International (2020) 97, 861–876
Definition KDIGO 2020, BP and volume control of in dialysis: conference report Intradialytic • Any symptomatic decrease in SBP or Hypotension • nadir intradialytic SBP < 90 mm Hg • should prompt reassessment of BP and volume management. JE Flythe et al. Kidney International (2020) 97, 861–876
Pathogenesis and causes of intradialytic hypotension UFR>10-13 ml/kg/hr ↑Mortality Comprehensive Clinical Nephropathy Ed 6th
Approaches to prevent and treat intradialytic hypotension Clinical Kidney Journal, Volume 13, Issue 6, December 2020, Pages 981–9
Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review • Six of 10 studies report improvement in symptoms of IDH, and there were no reported serious adverse events ascribed to midodrine. Nephrol Dial Transplant. 2004 Oct;19(10):2553-8. doi: 10.1093/ndt/gfh420.
Nonpharmacologic Interventions to Prevent Intradialytic Hypotension • Reduce UF rate Increase dialysis time Decrease weight gain Lengthen dialysis treatments Decrease sodium intake • Dietary counseling, including family members/food preparers • Dietary sodium restriction • Avoid sodium loading during dialysis Increase frequency of dialysis treatments Enhance non-dialytic volume loss Utilize home dialysis modalities • Diuretics • Gastrointestinal, sweat, and respiratory JE Flythe et al. Kidney International (2020) 97, 861–876
Nonpharmacologic Interventions to Prevent Intradialytic Hypotension • Enhance vascular space viability Cooled dialysate Isolated UF, followed by HD Higher dialysate sodium Hemodiafiltration Higher dialysate calciuma Improve venous tone (compression UF profiling stockings) Supine dialysis JE Flythe et al. Kidney International (2020) 97, 861–876
Nonpharmacologic Interventions to Prevent Intradialytic Hypotension • Improve overall health Prevent protein energy wasting Preserve residual kidney function Intradialytic exercise JE Flythe et al. Kidney International (2020) 97, 861–876
Residual Renal Function JE Flythe et al. Kidney International (2020) 97, 861–876
Contributors to and consequences of blood pressure and volume abnormalities in dialysis
Take Home Messages Diagnosis of Need the standard Period of BP readings No consensus BP target, Hypertension in dialysis technique should be used rather an ‘individualized patients in Thailand than spot one approach’ is necessary should be based on for all patients home BP > Office BP Sodium and Volume Treatment need to Beware of “Intradialytic overload is major and balance between Risk & hypotension” modifiable cause of HT Benefit
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