Calcium gluconate

This chapter is relevant to Section I3(ii) of the 2017 CICM Primary Syllabus, which expects the exam candidates to "describe the function, distribution, regulation and physiological importance of sodium, chloride potassium, magnesium, calcium and phosphate ions". It is only relevant because Question 4 from the first paper of 2011 asked the trainees to compare calcium chloride and calcium gluconate.

Calcium gluconate

The 10% calcium gluconate injection contains 1 g of active ingredient per 10ml vial. In these 10mls of water, each divalent molecule of calcium is wed to two molecules of gluconate ion. This gluconate ion is the conjugate base of gluconic acid of which much is made of in another chapter. Owing to the huge fat conjugate base, the calcium gluconate molecule has a molar mass of 430.373 g per mol. This is why calcium chloride ampules have more calcium in them. The excess baggage is the reason why the calcium chloride ampoule (which also contains 1g of active ingredient per 10ml) actually has more calcium than the gluconate.

The relevance of this

What does it matter, which calcium you reach for? Typically, there is no calcium chloride available where you work. Only in the enlightened ICU can one find this rare stuff. Is there a difference between calcium chloride and calcium gluconate, in terms of ionic calcium availability? 

Well. In the dark ages, the prevailing opinion was that calcium chloride is more immediately bioavailable. Writing in 1984, Heining et al noted:

"Several standard textbooks of anaesthesia and resuscitation state that calcium chloride is preferable to calcium gluconate injection because it causes a more rapid rise in plasma cCa²⁺"

This is because it was thought that at physiological pH some of the calcium gluconate (sources disagree as to how much) remains in a non-ionised state, as if crystals of calcium gluconate circulate around and wait for hepatocytes to crack them. The pKa of calcium gluconate (according to this industrial materials safety data sheet) is actually around 3.7, so its dissociation in the body fluids should be near-complete. In spite of this, it has been a long-held belief that the liver needs to somehow metabolise the gluconate in order for the calcium to become bioavailable. 

Thankfully, here is a study of patients without a liver to whom both calcium chloride and calcium gluconate were administered.  It has demonstrated that, contrary to popular belief, you do not need a liver to derive rapid and maximal benefit from calcium gluconate.

So then, what properties unique to this salt of calcium could one mention when they discuss the differences between calcium chloride and calcium gluconate?

• Pharmaceutical presentation: calcium chloride is a more concentrated salt. Grabbing one ampoule of calcium chloride is equivalent to grabbing three ampoules of calcium gluconate. Theoretically, it is therefore a timesaver, as one only needs to aspirate one stoppered vial instead of three (though one might argue that the twenty seconds saved represent only about 15% of a single cycle of CPR) Less instrumentation of ampoules is theoretically also protective against infection and decreases the risk of drug error.
• Chemical properties: The undiluted calcium chloride ampoule has an osmolality of around 2040 mOsm/kg, whereas calcium gluconate is merely twice-hypertonic to the body fluits, at 680 mOsm/kg. The pH of the undiluted chloride is also lower, 5.5-7.5 according to the manufacturer, whereas it is 6.0-8.2 for the gluconate salt. This is probably completely meaningless as the infusion would be rapidly buffered to near physiological pH by the body fluids.
• Irritant properties: calcium chloride is thought to be more irritant. Specifically, calcium chloride is classified as a "vesicant", i.e. it causes necrosis wherever it touches tissue (or if it extravasates). Infusing it into a small vein is therefore a recipe for vessel damage, clot formation, slough and abscess. That calcium gluconate is somehow safer is a widely believed fact; most people think that it is merely "irritant", i.e. it merely causes pain and only winks a coy hint of thrombophlebitis.  However, pharmacists typically keep it on their list of noncytotoxic vesicants, and where it is literally listed alongside calcium chloride. They both receive a "RED" rating, i.e. they are treated as equally dangerous.