NAION Intradialysis Countermeasures
NAION and Intradialysis hypotension
There are two classes of anterior ischemic optic neuropathy (AION): non-arteritic (NAION) and arteritic (A-AION; i.e., Temporal Arteritis (TA; aka Giant Cell Arteritis-GCA related). As the name NAION implies refers to ischemia of the optic nerve that is not associated with TA. The precise etiology of NAION remains ill-defined but hypotension has been proposed as a risk factor. One potentially treatable cause of hypotension is intradialytic hypotension (IDH). Although there is no universally designated definition for IDH, the kidney disease outcome initiative defined IDH as a decrease in systolic blood pressure by 20 or more mm Hg drop in baseline blood pressure or a decrease in mean arterial pressure by 10 mmHg associated with symptoms (e.g., abdominal discomfort, , nausea, vomiting, muscle cramps, restlessness, dizziness, fainting) 
As stated earlier, no exact cause has been found to exclusively account for occurrence of NAION. Vasculopathic risk factors (e.g., hypertension, diabetes, smoking, obstructive sleep apnea, and certain medications) have all been reported in NAIONS. Specific ocular risk factors that may promote but have not been proven to show a definitive association with the event include a small cup to disk ratio, optic disk drusen, and cataract surgery. Major factors that contribute toward this development include: autonomic neuropathy, rapid ultrafiltration, decreased cardiac reserve, and a low target weight and impaired autoregulatory mechanisms due to wide variations in blood pressures.
Sands et al reviewed the frequency of IDH and the sources of variation that influence clinical outcomes. This study illustrated that a variety influenced the increased occurrence of IDH. These factors included but we’re not limited to increased age, female gender, diabetes, longer duration of end stage renal disease (ESRD), higher ultrafiltration volume, higher dialysate pressure, and a higher difference between achieved and recommend post hemodialysis weight;; additionally, recently identified risk factors included elderly patients, large interdialytic weight gain (IDWG), tachycardia at the end of dialysis and heart failure.
A multitude of factors play a role in achieving an adequate blood pressure during dialysis. These factors include rate of ultrafiltration, autoregulatory mechanisms, and cardiac reserve. When these factors are affected, a negative impact is incurred on the body resulting a in a drop-in blood pressure(BP). It is this decreased BP and thus decreased perfusion that may promote the development of ischemia in the optic nerve.
Ultrafiltration is a method of fluid removal utilized during dialysis to remove solutes and chemical mediators from the intravascular volume. The rate at which this occurs is systematically set during dialysis and must be carefully balanced against the rate of refill of intravascular space from the interstitial space. The purpose of ultrafiltration is to remove fluid from the body to allow for a target weight or dry weight to be achieved. To achieve this goal of removal, the rate of ultrafiltration is adjusted, with parameters often utilizing rapid ultrafiltration. Hypotension results from the scenario in which the rate of ultrafiltration outcompete the rate of refill resulting in a symptomatically significant decrease in intravascular volume.
IDH may be related to autonomic insufficiency, although the exact mechanism remains unclear. It is thought dysfunction in the autonomic nervous system (ANS) may contribute to hypotension through a variety of ways: impaired HR and thus cardiac function during hypovolemia. Decreased arteriolar constriction due lack of sympathetic innervation, impairment in venous return due to reduction in constriction of veins and venules. These factors together playing a role to result in hypotension. Cardiac reserve by definition refers to the difference in the rate at which the heart pumps blood and its maximum capacity at any one-point int time. It refers to the ability of the heart to increase cardiac output to meet metabolic demands during exercise or maximal exertion. Certain conditions such as HF, ischemic heart disease, left ventricular hypertrophy (LVH) or coronary heart disease (CAD) impair the ability of the heart to increase CO. These factors especially CAD, impair the myocardial contractility and as such act as significant risk factors in the development of IDH
Peritoneal dialysis vs Hemodialysis both cause hypotensive events. In a study case from a peritoneal dialysis patient who suffered bilateral AION, the night readings on diastolic pressure were approximately 41 mmHg. Uremia on its own is associated to hypertension, hypotension, atherosclerosis, and anemia , all of which predispose to decreased blood-quality delivery<
Symptoms and Signs
NAION secondary to IDH will have a presentation similar to that of typical NAION and has common features with other optic neuropathy (e.g., decreased visual acuity, loss of color perception, a swollen optic nerve, and a relative afferent pupillary defect (RAPD)). The retrobulbar form of ION is referred to as posterior ION (PION) rather than AION. Although the disc appears normal acutely, over time patients with PION develop ipsilateral optic atrophy.
The diagnosis of NAION secondary to IDH is clinical only and there is no laboratory or radiographic feature that is diagnostic.
In the case of a sudden decrease in BP during dialysis, measures to regulate BP may be considered. Acute management of IDH is aimed at managing blood volume and the overall perfusion of the body. In the acute management of IDH, a number of steps could be considered to minimize possible adverse effects:
1. Placement of the patient in the Trendelenburg position. This could be considered as to optimize perfusion to the brain.
2. Change ultrafiltration rate may be beneficial
3. Connect oxygen monitor. Changes in O2 saturation may precede the development of IDH.
The European Best Practices Guidelines proposed counter measures stratified by level of importance ranging from First to Third line approaches.
1. Avoid intradialysis food intake
The proposed mechanism through which intradialytic food intake promotes hypotension is through vasodilation. Evidence has illustrated that the ingestion of food during leads to splanchnic vasodilation. This vasodilation leads to a decrease in peripheral vascular resistance and a result leads to a decrease in MAP. Ingestion of food may result in a drop in BP as little as 20 minutes following ingestion of food. This factor must be carefully examined and addressed in individual prone toward intradialytic hypotension.
2. Reduce sodium intake during dialysis
Sodium intake leads to accumulation of extracellular fluid, that directly influences the amount of ultrafiltrate fluid removed by dialysis. A sodium intake of 1-2 grams per day should be the goal.
3. Reassess target weight
Target weight is a parameter that intertwines closely with ultrafiltration and dialysis. This parameter plays an important role in the onset of hypotension through this connection. The overall goal of dialysis is to assist or to replace the function of the kidney is eliminating metabolic waste. A goal target weight is defined as a weight in which unfavorable symptoms such as nausea, vomiting, or hypotension are avoided. An accurate goal target weight and measurement of current weight is essential in preventing adverse effects. Scenarios in which the patient’s dry weight are over and underestimated play an important role in the outcome of the patient. If underestimated, this may lead to the patient presenting underhydrated secondary to a decrease in blood volume. This might result in hypotension.
4. Halt antihypertensive medications during dialysis
It seems obvious that avoiding short term anti-hypertensives would decrease IDH. ACE inhibitors, calcium antagonists, ACE inhibitors and nitrates were evaluated. Only the later was an independent risk factor but no real causation correlation was estimated in the study.
5. Prolonging dialysis time
By prolonging dialysis time, the ultrafiltration rate decreases which results in slower decline in blood volume.
6. Correct underlying anemia
Normal Hb leads to more oxygenated blood, however, no study has been performed to assess anemia effect in IDH.
Includes methods that have been shown to improve hemodynamic stability but with varying levels of risk and efficacy.
1. Assess cardiac risk factors
Evidence has shown underlying cardiac pathologies influence the functionality of the heart and may reduce cardiac output. Studies have shown that cardiac pathologies such as heart failure or cardiomegaly increase the risk of hypotension in the setting of dialysis. As such it is important to assess for primary cardiac factors.
2. Alternate schedule; Increase time/frequency of dialysis
Alternation in the scheduling and duration of the dialysis may play a role in reducing the occurrence of IDH. By changing the duration of the dialysis to increase the amount of time, the rate of ultrafiltration can be decreased. This reduction in the rate of ultrafiltration allows for a more gradual decline in blood volume, and reduction in episodes hypotension. An increase in the frequency of dialysis may allow for a reduction in episodes of IDH as well. Through shortening the duration of daily dialysis or increasing the frequency, more precise controlled of BP is allowed.
There are different methods to asses the relative blood volume (RBV), which tends to show a initial phase of fast drop followed by a slower decline in likely secondary to refilling of central veins; additionally there have been different methods tried, in order to accurately measure BV taking into account the difference between whole-body hematocrit (Ht) and systemic Ht.
3. Use cool dialysate
Dialysate refers to the solution that is introduced in the process of dialysis to remove metabolites from the body through diffusion. The components of this mixture vary but normally consist of sodium, bicarbonate, pure water, and other electrolytes. Changes in both the concentration and temperature, influence overall hemodynamic stability. The process of dialysis alone leads to an increase in the body’s core temperature. This increase in temperature subsequently leads to systemic vasodilation and a reduction in both capacitance and total peripheral resistance. In order to reduce the increase in core temperature, and resulting hypotension, EBPG guidelines have recommend the use of cool dialysate. The use of cool dialysate offsets the increase in body temperature, and thus prevents subsequent cascade of mechanism that leads to and exacerbate hypotension. One study showed that a drop-in temperature of dialysate was associated with an increase in the hemodynamic stability.
In the scenario that other treatment options fail to effectively address the hypotension, a tertiary approach may be utilized:
1. Use Midodrine
Midodrine is a selective alpha-1-adrenergic agonist that functions by causing peripheral arteriolar vasoconstriction and increased venous return. Evidence has shown that this drug may play a beneficial role in reducing the occurrence and symptoms of IDH, especially in ESRD patients
2. Change the form of dialysis
Peritoneal dialysis is not as continuous as hemodialysis, therefore, may help patients with intractable dialysis hypotension. However, there are some studies supporting that both peritoneal vs hemodialysis have no difference. There are no studies to shows statistical significance, however.
ION can occur after IDH. Specific countermeasures to reduce the risk of recurrent AION or PION from IDH should be discussed with the treating primary physicians and the hemodialysis team.
- Porter D, Vemulakonda GA. Blood Pressure. American Academy of Ophthalmology. EyeSmart® Eye health. https://www.aao.org/eye-health/anatomy/blood-pressure-list. Accessed January 06, 2023.
- ↑ Stefansson, Bergur V. “Intradialytic Hypotension and Risk of Cardiovascular Disease.” Clinical Journal of American Society of Nephrology, Vol.9(12) 2124-2132, Dec. 2014, cjasn.asnjournals.org/content/9/12/2124. Accessed June 9,2019
- ↑ Sands, Jeffrey J., et al. “Intradialytic Hypotension: Frequency, Sources of Variation and Correlation with Clinical Outcome - Hemodialysis International, John Wiley & Sons,– Vol 18, April 2014 – 415-422, https://onlinelibrary.wiley.com/doi/abs/10.1111/hdi.12138. Accessed June 9,2019
- ↑ Koda Y, Aoike I. Prevention of Intradialytic Hypotension with Intermittent Back-Filtrate Infusion Haemodiafiltration: Insights into the Underlying Mechanism. Blood Purif. 2019;48 Suppl 1:1-6. doi:10.1159/000503878
- ↑ 4.0 4.1 Peyronel F, Parenti E, Fenaroli P, et al. Integrated strategies to prevent intradialytic hypotension: research protocol of the DialHypot study, a prospective randomised clinical trial in hypotension-prone haemodialysis patients. BMJ Open. 2020;10(7):e036893. Published 2020 Jul 8. doi:10.1136/bmjopen-2020-036893
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Jeroen Kooman, Ali Basci, Francesco Pizzarelli, Bernard Canaud, Patrick Haage, Denis Fouque, Klaus Konner, Alejandro Martin-Malo, Luciano Pedrini, James Tattersall, Jan Tordoir, Marianne Vennegoor, Christoph Wanner, Piet ter Wee, Raymond Vanholder, EBPG guideline on haemodynamic instability, Nephrology Dialysis Transplantation, Volume 22, Issue suppl_2, May 2007, Pages ii22–ii44, https://academic.oup.com/ndt/article/22/suppl_2/ii5/1871254. Accessed June 6, 2019
- ↑ Sato M, Horigome I, Chiba S, Furuta T, Miyazaki M, Hotta O, Suzuki K, Noshiro H, Taguma Y. Autonomic insufficiency as a factor contributing to dialysis-induced hypotension. Nephrol Dial Transplant. 2001 Aug;16(8):1657-62. PubMed PMID: 11477170.
- ↑ Shemesh, Ari. “Sequential Nonarteritic Anterior Ischemic Optic Neuropathy in Patient on Chronic Hemodialysis.” Department of Ophthalmology, Springer CEN Case Reports, Vol. 8(2): 89–9421 Nov. 2018, ophthalmology.utoronto.ca/news/journal-publications. Accessed June 9,2019
- ↑ Sabt BI. Anterior ischemic optic neuropathy and dialysis: Effect of hypotension. Oman J Ophthalmol. 2013;6(1):64-65. doi:10.4103/0974-620X.111934
- ↑ 9.0 9.1 Hammes, Mary, and George L. Bakris. “Intradialytic Hypotension: Is Midodrine the Answer?” American Journal of Nephrology, Karger Publishers, Vol 48. No.5,13 Nov. 2018, www.karger.com/Article/FullText/494805. Accessed June 9,2019
- ↑ Knoll, Greg A., et al. “A Randomized, Controlled Trial of Albumin versus Saline for the Treatment of Intradialytic Hypotension.” American Society of Nephrology, American Society of Nephrology, 1 Feb. 2004 jasn.asnjournals.org/content/15/2/487.Accessed June 6,2019
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- ↑ Dasselaar JJ, Lub-de Hooge MN, Pruim J, et al. Relative blood volume changes underestimate total blood volume changes during hemodialysis. Clin J Am Soc Nephrol. 2007;2(4):669-674. doi:10.2215/CJN.00880207
- ↑ Sande, Frank M. van der, et al. “Control of Core Temperature and Blood Pressure Stability during Hemodialysis.” American Society of Nephrology, American Society of Nephrology, Vol 4 (1) 93-98, 1 Jan. 2009, cjasn.asnjournals.org/content/4/1/93. Accessed June 9,2019
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