Is correcting hyperchloremic acidosis beneficial?

Clinical Question

An elderly woman presents with renal failure due to severe dehydration from diarrhea. She has a hyperchloremic acidosis from diarrhea with a chloride of 115 mEq/L, bicarbonate of 15 mEq/L, and a normal anion gap. During her volume resuscitation, should isotonic bicarbonate be used to correct her hyperchloremic acidosis? Does correcting her hyperchloremic acidosis actually help her, or does this just make her numbers better?

Introduction

The use of bicarbonate for treatment of metabolic acidosis is controversial. However, this controversy centers primarily around use of bicarbonate for management of lactic acidosis or ketoacidosis. Treatment of these disorders requires reversing the underlying disease process, with bicarbonate offering little if any benefit. Hyperchloremic metabolic acidosis is different. Whether due to bicarbonate loss or volume repletion with normal saline, the primary problems is a bicarbonate deficiency. Treating this with bicarbonate is a logical and accepted approach:

Giving bicarbonate to a patient with a true bicarbonate deficit is not controversial. Controversy arises when the decrease in bicarbonate concentration is the result of its conversion to another base, which, given time, can be converted back to bicarbonate

– Sabatini 2009

However, clinicians are often reluctant to treat hyperchloremic metabolic acidosis with bicarbonate, since the benefits of treatment are unclear. This post will attempt to clarify the rationale for treatment.

Resuscitation with balanced crystalloids improves renal function

There is growing evidence that resuscitation with normal saline impairs renal blood flow and function (Young 2014). For example, Chowdhury 2012 investigated the effects of two liters of normal saline or plasmalyte administered over an hour to normal volunteers. Normal saline reduced renal artery flow velocity and renal cortical perfusion by about 10%:

Yunos 2012 performed an open-label prospective study evaluating the effect of a restricting the use of chloride-rich fluids among critically ill patients. Implementation of a chloride-restrictive strategy reduced the incidence of renal failure and the need for dialysis:

Improved outcomes with balanced crystalloids reflects avoidance of hyperchloremic acidosis

Although balanced crystalloids are gaining popularity, there is nothing majical about these fluids themselves. The primary “class effect” across various balanced crystalloids is avoidance of hyperchloremic acidosis. Thus, rather than thinking about these studies as “normal saline versus balanced crystalloid,” it may be more accurate to think about them as studies of “volume expansion with or without generation of a hyperchloremic acidosis.” From this perspective, it becomes clear that hyperchloremic acidosis is not benign.

Why does hyperchloremic acidosis impair renal function?

Hyperchloremia is known to reduce renal blood flow. This is due to alteration of tubuloglomerular feedback, a mechanism normally used by the kidney to auto-regulate the glomerular filtration rate:

Normally, if the glomerular filtration rate increases excessively, then the proximal nephron is unable to absorb the filtered sodium chloride. This causes an increase in the concentration of chloride delivered to the distal nephron. The macula densa in the distal nephron senses this increased chloride concentration, triggering vasoconstriction of the afferent arteriole with a subsequent decrease of glomerular filtration rate back to normal. Sounds great!

Unfortunately, if the chloride concentration in the blood is elevated, then this leads to a high chloride concentration in the distal nephron despite a normal glomerular filtration rate. The macula densa is stimulated by this high chloride concentration, leading to vasoconstriction of the afferent arteriole and reduced glomerular filtration rate. Essentially, hyperchloremia causes the tubuloglomerular feedback mechanism to over-estimate the glomerular filtration rate, ultimately leading to a decrease in glomerular filtration rate (Lobo 2014).

Other reasons to correct hyperchloremic acidosis

Hyperchloremic acidosis will trigger a compensatory respiratory alkalosis, which increases the work of breathing. In most situations this is not very significant, but for patients with shock or respiratory failure this may be undesirable.

Given that hyperchloremic acidosis is often iatrogenic, and associated with morbidity, it should be avoided whenever possible
– Kellum 2006

It is also possible that hyperchloremic acidosis may worsen inflammation during septic shock and cause impaired coagulation (Kellum 2006). The clinical relevence of these findings remains unclear (Guidet 2010).

Conclusions

Experiments comparing normal saline to balanced crystalloid show that hyperchloremic acidosis impairs renal blood flow and function. This is likely due to vasoconstriction of the afferent renal arterioles in response to hyperchloremia. Although indirect evidence, this suggests that correcting a hyperchloremic acidosis offers benefit to the patient, rather than merely fixing the numbers.

Correction of hyperchloremic acidosis is often accomplished with intravenous isotonic bicarbonate (150 mEq/L), which may require a substantial amount of volume. There is little risk involved in the judicious use of isotonic bicarbonate for a patient who is volume depleted, so correcting a hyperchloremic acidosis makes sense during volume resuscitation (as discussed in a prior post about pH-guided resuscitation). The value of isotonic bicarbonate in a euvolemic patient is unclear, but may be reasonable if the patient has renal injury. For a hypervolemic patient, volume removal with a loop diuretic will improve both volume status and bicarbonate level simultaneously.

Therefore, rather than the exact fluids used for a resuscitation, the most important aspect may be avoiding a hyperchloremic acidosis (i.e., achieving “euchloremia”). For example, if a patient presents with a hyperchloremic acidosis prior to resuscitation, it may be better to correct this with isotonic bicarbonate (an “imbalanced” fluid) instead of using a balanced fluid. Ultimately, it's more important to have a balanced patient than a balanced IV fluid.

This is the first of a series of three posts about preserving renal function in critically ill patients. We're just getting started. Stay tuned.

Image credits:

– Acid: http://www.freeimages.com/photo/danger-acid-1252132

– Tubuloglomerular feedback: http://pblh2012.wikispaces.com/Week+23+-+Starting+Work