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Introductory case
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A young 70-kg man was transferred to the Genius GeneralICU for management of stupor. He had been diagnosed with aortic valve endocarditis due to heroin abuse two weeks earlier, but left the hospital against medical advice. Shortly after admission to Genius General, the lab called with a critical sodium value of 122 mM. Review of records from the outside hospital showed that his sodium had been 124 mM a few hours earlier. So, his hyponatremia was real and it was falling rapidly. He was immediately treated with two 50-ml ampules of 8.4% sodium bicarbonate. Repeat sodium showed an increase to 125 mM:
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Over time his mental status and sodium both normalized.
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Introduction
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“Prompt infusion of hypertonic saline may save lives and preparing a 3% hypertonic saline infusion takes time. In addition, errors may occur from having to calculate the required amount of sodium chloride in an emergency.”
– European hyponatremia guidelines 2014
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When hypertonic therapy is needed, it is often needed immediately. A patient with herniation or hyponatremic seizures needs hypertonic therapy now, not in ten minutes when it arrives from pharmacy. For example, I once ordered a head CT and hypertonic saline for a patient with suspected herniation, but the hypertonic saline arrived in the ICU after the patient had already left for CT scan. Hypertonic sodium bicarbonate may provide a solution to this logistical problem.
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Understanding 8.4% sodium bicarbonate
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The osmolarity of 8.4% bicarbonate is 2000 mOsm/liter, which would be equivalent to the osmolarity of 5.8% NaCl. Thus, 8.4% bicarbonate for osmotherapy may be conceptualized as “6% saline.” This makes it twice as powerful as the traditional hypertonic agent, 3% NaCl. For example, instead of bolusing with 100 ml of 3% NaCl, you could bolus with 50ml of 8.4% bicarbonate (one ampule).
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Many trainees feel comfortable bolusing two amps of bicarb, but would be afraid to bolus 200 ml of 3% NaCl. This is illogical, since both therapies provide essentially the same amount of osmotherapy. Similar irregularities exist in the literature as well.
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Dose for symptomatic hyponatremia
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Guidelines and review articles agree that for a patient with hyponatremia and severe symptoms (e.g. seizures or coma), an increase of sodium by 5 mM should be adequate to relieve symptoms and avoid danger. However, the amount of hypertonic therapy recommended in many sources is inadequate. For example, a 2015 review article in the New England Journal contains the following table:
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Although 100 ml of 3% saline may seem like a lot, it isn't. For example, if 100ml of 3% NaCl were given to the patient at the beginning of this post, it would increase his sodium by 0.9 mM according to the Androgue-Madias formula (MedCalc).
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The European 2014 guidelines recommend treating emergent hyponatremia as shown above. Note that they recommend checking a sodium level simultaneously with the seconddose of 3% NaCl, such that every patient would receive a minimum of 4 ml/kg 3% NaCl. Based on the Androgue-Madias equation, 4 ml/kg 3% NaCl should increase the serum sodium by ~3 mM. The guidelines then recommend additional hypertonic therapy until the sodium increases by 5 mM/L. This is more aggressive than most articles recommend (e.g. a 70-kg patient would receive a minimum of 280 ml 3% NaCl).
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In practice, it is logistically tricky to provide two doses of 2 ml/kg 3% NaCl and measure the sodium simultaneously with infusion of the second dose (especially if other events are occurring, such as status epilepticus). It may be simpler to provide the patient with a single dose of 4 ml/kg 3% NaCl and check the sodium afterwards.
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Providing a larger dose (i.e. 4 ml/kg 3% NaCl) before repeating a sodium level will allow more precise determination of the effect of the bolus. For example, suppose you give 100ml of 3% NaCl and the sodium increases from 115 mM/L to 116 mM/L. Due to rounding error, a lab value of “115” mM/L could represent anything between 114.5-115.4 mM/L and “116” mM/L could represent anything from 115.5-116.4 mM/L. Therefore, an increase from “115” mM/L to “116” mM/L could represent an increase of anywhere between 0.1 – 1.8 mM/L. This can be misleading.
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Converting 4 ml/kg 3% NaCl to sodium bicarbonate would suggest that the initial dose should be 2 ml/kg of 8.4% sodium bicarbonate (e.g. a 70-kg patient would receive 140 ml of bicarbonate, or nearly three 50-ml ampules). For slightly less dire situations, this could be rounded down to 100 ml (two 50-ml ampules; equivalent to 200ml 3% saline).
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Evidence regarding the increase in sodium following 8.4% sodium bicarbonate
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Gutierrez 1991 studied the effect of 1 ml/kg boluses of 8.4% sodium bicarbonate among eight patients with renal failure and hyperkalemia. On average, this increased the serum sodium by 1 mM/L.
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Kim 1996 studied the effect of 120 ml 8.4% bicarbonate among eight patients with end-stage renal disease with weight ranging from 55-65 kg. On average, this ~2 ml/kg dose caused sodium to increase by 2 mM/L.
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Bourdeaux 2010 studied the effect of 85ml boluses of 8.4% sodium bicarbonate among ten episodes of elevated intracranial pressure. On average this increased the sodium by 1.6 mM/L. Given that 85ml is probably a bit over 1 ml/kg for most patients in this study, this study would suggest that a 2 ml/kg bolus of 8.4% sodium bicarbonate should increase the sodium by about 2-3 mM/L.
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Overall, these data support the concept that a 2 ml/kg bolus of 8.4% sodium bicarbonate would increase the serum sodium by around 2-3 mM. This would be a reasonable first step for the management of severe symptomatic hyponatremia.
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Dose for ICP elevation
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Recent trends in neurocritical care are moving away from mannitol and towards hypertonic saline for osmotherapy of elevated intracranial pressure (ICP). Hypertonic saline might be more effective. Furthermore, hypertonic saline doesn't cause diuresis and is more straightforward to monitor (serum sodium is easier to interpret and trend than serum osmolarity).
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The ideal dose of hypertonic saline is unclear, with substantial variation between various studies. Typically sequential boluses are used with titration to effect. Below are commonly used doses of 3%, 7.5%, and 23.4% NaCl (Ropper 2012, Bourdeaux 2010, Ennis 2011). To facilitate comparison, these doses have been converted into equi-osmolar doses of 3% NaCl and 8.4% sodium bicarbonate.
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This data would suggest that 80-120 ml of 8.4% bicarbonate may be a reasonable dose for management of intracranial hypertension (i.e. about two 50-ml ampules).
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Evidence regarding 8.4% sodium bicarbonate use in elevated intracranial pressure
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Bourdeaux 2010 performed a prospective observational study of the effect of 85ml sodium bicarbonate over 30 minutes during ten episodes of elevated ICP among seven patients with traumatic brain injury. The average ICP fell from 28 mm to 10 mm (figure below). There was no statistically significant change in pH.
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Bourdeaux 2011 performed a RCT comparing 100ml of 5% NaCl vs. 85ml of 8.4% sodium bicarbonate (equimolar doses). Twenty episodes of elevated ICP were studied among eleven patients with traumatic brain injury. There was no difference in the fall in ICP during the first 60 minutes following either treatment. However, after 150 minutes the mean ICP was higher in the hypertonic saline group, with two patients in the saline group needing repeat dosing of hypertonic therapy (figure below).
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Safety & Contraindications
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Safety of sodium bicarbonate
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8.4% sodium bicarbonate is a familiar drug which is reasonably safe. Ideally it should be given via a central vein, but in emergencies it is frequently given via a peripheral vein. Although previously thought to reduce potassium, hypertonic bicarbonate has little effect on potassium (explored previously here).
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Bicarbonate does have an alkalinizing effect. For example, a dose of 2 ml/kg 8.4% sodium bicarbonate may increase the serum bicarbonate concentration by ~5 mM (Kim 1996, Kim 1997). For most patients this will leave the serum bicarbonate well within a safe range. Patients receiving repeated therapy with hypertonic saline often develop a dilutional non-anion gap metabolic acidosis, so the intermittent use of hypertonic bicarbonate could be helpful to correct this. In a patient with significant metabolic or respiratory alkalosis, bicarbonate would be contraindicated.
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Over-correction of hyponatremia
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Over-correction of hyponatremia is common, but this is rarely a direct effect of the infused solution. Instead, over-correction is usually due to excessive excretion of free water by the kidneys. The physiology, prevention, and management of sodium over-correction will be explored in detail next week.
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- 8.4% sodium bicarbonate has about the same osmolarity as 6% NaCl, making it about twice as powerful as 3% NaCl.
- For severe symptomatic hyponatremia (e.g. seizures or coma), initial treatment with 2 ml/kg of 8.4% sodium bicarbonate is reasonable. For less dire indications, ~1.5 ml/kg of 8.4% sodium bicarbonate may be used initially (which will often be about 100ml, or two 50-ml ampules).
- For elevated intracranial pressure, 80-120 ml of 8.4% sodium bicarbonate is a reasonable initial dose (e.g. two 50-ml ampules).
Key hyponatremia reference: In 2014 an epic evidence-based guideline on hyponatremia was produced by a consortium of the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology, and the European Renal Association. Free full-text here.
Stay tuned, this is the first of a three-part series about hyponatremia. Next week we will discuss preventing over-correction of the sodium. The third post will discuss extremely unconventional approaches to hyponatremia.
Image Credits: https://en.wikipedia.org/wiki/Baking_powder
Josh is the creator of PulmCrit.org. He is an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont.
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Will 300ml of normal saline do the same as 100ml of 3% nacl?
As you stated it might take time to get it when you need it.
Great blog.
How fast would you give the bicarb in a situation of status epilepticus?
Absolutely agree. This is another strength of bicarb amps: with an osmolality of 2000 mOsm/L, they will always increase the serum sodium (even in profoundly severe SIADH with a very high urine osmolality).
great post. also i think in siadh it's important to look at the Uosm, because if you give a fluid with lower osmolarity whether it be LR or NS or HS, you may just be worsening the situation.
Nothing serious but you might want to fix broken links to Genius General Hospital in the text of the article that currently point to https://emcrit.org/p/genius-general-hospital.html instead of https://emcrit.org/janus-general/
STerns advises 100 mL 3% NaCl boluses in 10-15 min , up to 3 , for severe hypoNa with seizures or coma
Sterns RH. Disorders of plasma sodium–causes, consequences, and correction. N Engl J Med. 2015 PMID: 25551526
Sterns RH. Overview of the treatment of hyponatremia in adults. Uptodate Fev 2017.
So 50 mL up t 3 times of 8.4% bicarbonate would do ?
Great post. I am wondering what the your thoughts are on the use of hypertonic bicarb in cerebral edema associated with pediatric DKA specifically, where it appears that bicarbonate use is associated with the DEVELOPMENT of cerebral edema and is supposed to be avoided so as not to cause it in the first place.
Don’t know. Sorry, I only manage adult patients.
Excellent post. Many medics believe sodium bicarbonate’s sole role is as an alkalizing agent for condition such as the classic “tricycle OD” treatment, yet (one of its) strength is in overcoming sodium channel blockade thanks to its sodium load which is equivalent to 325 mL of isotonic saline.
Is there anything distinct about the pathophysiology of DKA, especially pediatric DKA, that would contraindicate sodium bicarbonate use as a method of acutely (like, herniating now) decreasing ICP?
Hi Max! mannitol is the most used treatment for cerebral edema in DKA