Monday, January 3, 2011

Intradialytic hypertension

I’ve recently had a few calls from our outpatient dialysis unit about patient’s with rises in their blood pressure during and after dialysis. Intradialytic hypotension is a very common phenomenon and it’s been interesting to learn that intradialytic hypertension also occurs quite frequently with a reported prevalence of up to 15%.

The relationship between blood pressure and clinical outcome in hemodialysis patients is complex and both the most predictive type of measurement and optimal target value are unknown. As a matter of practicality, The Handbook of Dialysis recommends targeting pre dialysis blood pressures of <130/80 with less strict goals in patients with wide pulse pressures or at risk for orthostasis. Intradialytic hypertension has been defined in a number of ways but basically refers to patient’s whose intradialysis or post dialysis BPs are higher than their starting values. It has been associated with increased hospitalization and mortality in hemodialysis patients.

Why it occurs is unknown but several theories have been put forward:

1) Volume overloadAnimal chronic kidney disease models suggest that chronic sodium and volume overload can lead to sustained elevations in blood pressure though increases in peripheral vascular resistance. On the molecular level sodium leads to the release of digitalis-like factor which inhibits the Na/K ATPase on vascular smooth muscle leading to increases in both intracellular sodium as well as calcium. These rises in intracellular calcium then cause smooth muscle contraction with increases in vascular resistance. In addition, dialysis patients with little or no residual renal function are not able to urinate off excess volume leading to rises in preload and cardiac output.

So the above provides an explanation as to why sodium mediated volume overload might lead to hypertension but why would blood pressure rise further with ultrafiltration on dialysis?

Some studies suggest that as volume is removed in overloaded patients cardiac output and blood pressure rise, presumably as the heart is put in a more favorable portion of the starling curve though evidence for this is conflicting. Alternatively a recent review tied together the volume overload and endothelin hypotheses (see below) by suggesting that faster intravascular refilling in volume overloaded patients resulted in more mechanical stress triggered endothelin-1 release with subsequent rises in peripheral vascular resistance.

2) Endothelial cell dysfunction – In response to volume changes, mechanical stress and hormonal stimuli endothelial cells synthesize and release factors that contribute to BP homeostasis. Severalstudies to date have looked at this and have shown greater rises in the vasoconstrictor endothelin-1 in patients with intradialytic hypertension when compared with controls. The largest study supporting this hypothesis also showed that intradialytic rises in blood pressure were largely due to rises in peripheral vascular resistance rather than cardiac output. Of interest, there is a currently enrolling NIH trial looking at carvedilol's impact on intradialytic hypertension due to it's potential to suppress endothelin-1 release.

3) Dialytic removal of antihypertensives – Many blood pressure medications including multiple beta-blockers and ACE inhibitors are significantly removed during dialysis. Although removal of these agents is a potential contributor in some cases, intradialytic hypertension still occurs in patients who are off all BP meds.

4) Erythropoetin stimulating agents – Intravenous administration has been associated with elevations in blood pressure in dialysis patients and interestingly also with elevations in endothelin-1.

5) Sympathetic overactivity, RAAS activation, electrolytes – Volume removal followed by upregulation of homeostatic systems is often cited as a possible cause of intradialytic hypertension. However, a recent study that measured plasma catecholamines and renin in patients with and without intradialytic hypertension pre and post dialysis found that renin and norepinephrine were actually higher in controls post dialysis. Dialysis induced reductions in serum potassium and elevations in calcium have also been postulated as possible causes but in the same study no significant difference between groups in these electrolytes was found. Intradialytic sodium gain due to higher dialysate than plasma sodium has been suggested as a possible cause of intradialytic hypertension but has not been directly studied.

Interventions targeting improvements in intradialytic hypertension have not been evaluated in randomized prospective fashion and the optimal treatment approach and benefit, if any, is unknown.

When I get the phone call I’ve been making sure the patient is asymptomatic then depending on the details of the blood pressure, I ask the patient and nursing staff if I can extend the run and increase the ultrafiltration goal (two small case series support this approach). If the BP remains elevated after dialysis, I will ask the patient to take an additional dose of one of their antihypertensives and I make note to review their medications, epo dosing, labs, dialysis regimen and dry weight.

I’d be interested to hear how others deal with this dilemma.

4 comments:

Michelle said...

I'm just curious...do any of your patients who do daily home hemo or perhaps nocturnal have these same difficulties? Or, is this something you see mainly in patients undergoing the usual thrice weekly incenter modality?

Joel Topf said...

Bullet two is missing the end of its sentence.

Graham Abra said...

Dr Topf, thank you for the editorial assistance.

Graham Abra said...

Michelle, unfortunately as a first year nephrology fellow I can count on my hands the number of home hemo and nocturnal dialysis patients that I've taken care of so my experience with these modalities is limited.

The recently published FHN trial looking at 6x per week as compared with 3x per week in center hemodialysis did not specifically look at intradialytic hypertension but did show a significantly lower pre-dialysis SBP with less antihypertensive med use in the 6x per week group.

These results are exciting for both patients and their physicians and I hope to gain more experience with frequent dialysis and modalities like it. I would guess that dialysis regimens that provide better volume control would lead to a lower incidence of intradialytic hypertension but this is something that remains to be proven in randomized control trials.