Hemodialysis in chronically hypotensive patient. Rajeev A Annigeri. Nephrology Consultant, Apollo Hospitals, Chennai.

Outline of talk. Definition of intradialytic hypotension (IDH). Chronically hypotensive HD patient Definition, prevalence, patient characteristics. Impact of IDH on clinical outcome. Pathophysiology of IDH. Interventions to prevent IDH.

Intradialytic hypotension (IDH): definition. “Decrease in SBP 20 mm Hg or MAP >10 mm Hg, associated with clinical events and need for nursing intervention”. Intervention may be IV saline administration, Trendelenburg position. Asymptomatic SBP <90 mm Hg should be considered as hypotension. Let me begin with the definition of IDH. Till recently there was no concensus of the definition of IDH. In the last decade a broad definition has evolved which is accepted by KDOQI as well as European Best practice guidelines. So it has three components namely drop in BLOOD PRESSURE, adverse symptoms and need for intrevention. However, some believe that drop in SBP below 90 mm Hg irrespective of whether it is sysmptomatic should be considered as IDH. And this is relevent to the the chronically hypotensive patients some of who may be asymptomatic at BLOOD PRESSURE of less than 90 mm Hg. 1, EBPG, NDT 2007 2, K/DOQI Am J Kidney Dis. 2005

Incidence of IDH. Incidence of IDH 20%1. Varies widely across the units. HEMO study: 16-18%. Literature indicates that the incidence of IDH is 10-30% of dialysis sessions, but my own experience is that it is lower than that. Even in HEMO study were close monitoring was done it was 16-18%. Idh is one of the quality monitors in our dialysis unit and incidence is about 1%. 1, Daugirdas JT, Kid Int 1999

Chronically hypotensive patient on HD. HD patient who has interdialytic blood pressure below 110 mm Hg. Prevalence 3-5% in HD unit. My talk focuses on the subgroup of patients who have low BLOOD PRESSURE even in the interdialytic period. Fortunately the incidence of such patients is only 3-5% and they pose a major challenge to dialysis nurses and physicians. Dheenan et al, Kidney Int 2001

Chronically hypotensive patient on HD. Patient characteRIstics Pathological defects Advanced age. Diabetes mellitus. Cardiac disease. Amyloidosis. Nephrotic state. Chronic liver disease. Malignancy. Malnourished. Cardiac dysfunction. Autonomic dysfunction. Severe hypoalbuminemia. Peripheral vasodilatation and pooling of blood. Chronically hypotensive patient has one or more of the following characteristics. The reason for low interdialytic BP in them is one or more of the following. Cardiac dysfunction as well as autonomic dysfunction are not uncommon in diabetic patients and amyloidosis. Severe hypoalbuminemeia again is seen in nephritic syndrome and peripheral pooling of blood is often seen in liver cirrhosis. Santos et al, Adv Chronic Kidney Dis 2012

IDH: clinical impact. Mortality Hospitalization Having intradialytic Sand et al, Hemodial Int 2014

Causes of death. Tisler et al, NDT 2001

Increased risk of AV fistula thrombosis. Chang T, JASN 2011

Complications of recurrent IDH. Reduced efficiency of dialysis. Compartmentalization leading to sequestration of uremic toxins. Reduced time on dialysis. Organ ischemia. Brain: cerebro-vascular events. Gut: ischemia, gram negative sepsis.

Pathogenesis of IDH.

Pathophysiology of IDH Fluid shifts Rate of UF Impaired response to fluid removal. Cardiac. Autonomic response. Vascular response

Manipulating Starling forces to prevent hypotension during HD. ICF ECF IVC Dialyzer 3L Increase tonicity of ECF Volume contraction of ECF Reduce UF rate Increase tonicity of dialysate Increase tonicity of plasma

Change in plasma osmolality during HD. Van Stone et al, AJKD 1982

Cardiac response to UF. Decreased EDV of LV Reduced mechanoreceptor stimulation in LV Vagal inhibition withdrawn. Activates sympathetic nervous system. Increases heart rate and force of contractility of LV.

Baroreceptor reflex. Sympathetic activity. Catecholamine release. Activation of RAS. Vasopressin release.

Impaired Baroreceptor sensitivity. Baroreceptor sensitivity (BRS) is well preserved in most HD patients. A subset of IDH prone HD patients may have baseline impaired BRS and can be identified by appropriate tests.

Bezold-Jarisch reflex: paradoxical withdrawal of vasoconstrictor respnse during HD. Converse et al, Clin Invest 1992

Impaired cardiac response. LVH, LV diastolic dysfunction. Reduced myocardial reserve. left ventricular hypertrophy, uremia induced myocardial fibrosis, down regulation of -adrenergic receptors in response to high levels of catecholamines Subclinical myocardial ischemia Myocardial stunning

Role of vascular tone Adenosine. Nitric oxide. Adrenomedullin. De Jager-Krogh effect Mediators of vasodilatation Adenosine. Nitric oxide. Adrenomedullin. Increase in core body temparature. Cytokines (Bioincompatibility)

Summary of pathogenesis of IDH.

Interventions to prevent IDH.

Optimization of method and rate of ultrafiltration(1) Reduce inter-dialytic weight gain Salt restriction. Increased frequency of HD (2-3 hours, 4-6 days a week). Longer duration of HD. Intradialytic administration of hypertonic solutions during early part of HD: 3% saline, 25% glucose, Mannitol 20%, Albumin 20%.

Optimization of method and rate of ultrafiltration (2). Increase DNa: Sodium profiling. UF profiling: isolated or combined with sodium profiling. Isolated UF. Sequential dialysis and UF Automatic biofeedback-controlled HD system.

Accurate measurement of dry weight: Bio-impedance analysis (BIA). Inferior vena cava (IVC) diameter and its dynamic variability during respiratory cycle. Measurement of pro-brain natriuretic peptide. Blood volume monitor.

Optimization of cardiac function Abdominal binder (inflatable). Intradialytic inotropes and vasopressors: Dopamine, dobutamine, vasopressin Intradialytic echocardiography.

Improving vascular tone. High dialysate calcium. Midodrine: Α1 agonist, oral, 2.5 to 20mg Given half hour before start of HD and during. Safe and effective. Cooling of dialysate: Dialysis is thermogenic (0.6oC). Sympathetic activity causes vasoconstrction and increases core temperature. Increase in core body temperature ultimately causes vasodilatation.

Interventional studies in IDH. Few studies Small studies Very few randomized studies

Comparison of multiple interventions. 10 patients with IDH were randomized to 5 different HD protocols, each lasting for a week. HD protocols: Standard HD High Dna (144 mmol/L). Na profiling (Dna 152 reduced to 140 mmol/L half hour before the end of HD). Isolated UF for one hour followed by 3 hours of isovolemic HD. Cool dialysate (35oC) Dheenan et al, Kidney Int 2001,

IDH and adverse events The best results were seen in sodium profiling followed by cool dialysate. It is tempting to think that combining sodium profiling and cool temperature would provide additive effect, but unfortunately it does not seem to be as seen in a small study. Sodium profiling is better intervention to prevent IDH

Sodium and UF profiling. 11 patients, prone for IDH. Each patient had 266 sessions of HD randomized to receive 8 HD protocols, each protocol for 33 sessions. Song et al, JASN 2005

8 Protocols for randomization. This study compared 8 protocols. 3 diferent types of sodium profiling and three different types of UF profiling.

Incidence of IDH.

Sodium balance and target weight achieved. Achievement of dry weight

Blood pressure control.

Adverse events in 6 months (events per patient).

Body water distribution.

Midodrine for IDH: meta-analysis. Prakash S et al, NDT 2004

Intradialytic BV monitoring. Reddan et al. JASN 2004

Outcomes worse in Crit-line monitoring. IDH similar in both groups (7% vs. 6%)

BV monitoring in IDH prone patients. Randomized cross over study. Conventional vs. BV monitoring over 8 months. Santoro, Kid Int 2002

Bio-feedback HD systems: ABV, ABT and ABP. INPUT Automated bio-feedback systems are the leap forwards in terms of preventions of IDH. We have automated feeebacks to Mancini et al, NDT 2007

Impact on IDH. P=0.02

Clinical approach to dialysis in hypotensive patient. Efficacy Availability Simplicity and Safety Cost

Step1: Salt intake to bare minimum, if interdialytic weight gain is high. Avoid food, just before or during HD. Assess dry weight by BIA. Cool the dialysate temperature to 36.5oC and if tolerated reduce further to 36oC.

Step 2: Increase the duration of HD. Sequential UF and Dialysis. Use pre dialysis oral midodrine 2.5 mg to begin with and increase dose if required stepwise to 10mg to achieve the desired result. Use combined sodium and UF profiling. Use sodium-neutral profiling protocol. Increase the dialysate calcium concentration if ionized blood calcium is not high. Consider Hemodiafiltration.

Step 3: Consider 100 ml of 25% glucose administration (in non-diabetics) and 3% sodium chloride 100ml during first one hour of dialysis, if sodium profiling causes increased intradialytic weight gain. Intradialytic dopamine administration (5-10 mcg/kg/min). Daily short HD. Transfer to peritoneal dialysis (PD) or do combined HD and PD.

r_annigeri@yahoo.com