Diabetic ketoacidosis is a state of insulin deficiency, characterised by rapid onset, extreme metabolic acidosis, a generally intact sensorium, and only mild hyperglycaemia. DKA comes up frequently in the CICM SAQs, but usually as an ABG interpretation exercise. This chapter focuses on the medical side of DKA, including its causes, manifestations, complications, and management strategies. Questions which have required such thinking have included the following:
How does one discriminate between DKA and HONK even when in about 30% of instances the two disorders coexist? Arbitrary definitions exist, proposed by the American Diabetes Association.
Features suggestive of DKA
Features suggestive of HONK
DKA requires a trigger. This takes the shape of a fairly binary distinction. Either there has been an absolute lack of insulin, or the tissue response to insulin has been decreased.
Lack of Insulin
Drugs which trigger DKA
Physiological stress tends to provoke a stress response - I suppose that is why they call it "the stress response". As a part of this response, neurohormonal influences on fuel metabolism promote the mobilisation of metabolic substrates, with some associated insulin resistance and with a decrease in endogenous insulin secretion (driven by the sympathetic nervous system as well as by circulating adrenaline). One of the consequences of this is "stress-induced hyperglycaemia" which can turn a non-diabetic person hyperglycaemic. One can imagine what this sort of response would do to a person with a preexsiting insulin intolerance, or pancreatic endocrine defect.
The basis of ketosis is the reduction in the effect of insulin, coupled with the increase in the action of anti-insulin hormones such as glucagon, cortisol, catecholamines and human growth hormone. Much of the physiology which underlies this is covered in the chapter on the physiological response to starvation.
In essence, there are three components, which can contribute unequally:
Ketones are acidic. The acidosis which develops due to an excess of ketones is discussed in the section on metabolic acidosis. Additionally, a lactic acidosis can develop in association with ketoacidosis. And on top of that, there are now an excess of free fatty acids in the bloodstream, which are also acidic (but which do not contribute extesnively to the acidosis per se.)
The ketone bodies - with the exception of acetone - are well dissociated at physiological pH, and produce a nice excess of hydrogen ions. The result is a depletion of the buffering systems, and a drop in pH.
Question 6 from the second paper of 2023 asked about the pathophysiology of euglycaemic ketoacidosis in a patient taking dapagliflozin. "Euglycaemic" ketoacidosis is essentially the same as starvation ketoacidosis, with the exception of the fact that the patient is often presenting with a normal oral intake. The main mechanisms, as outlined by Long et al (2021), are:
One can view HONK as a "pre-ketotic hyperglycaemia". The key pivot point where HONK can progress to ketosis seems to be the glucagon-driven initiation of lipolysis, which leads to the synthesis of all the offensive ketones. The difference in HONK is that there is still enough insulin around to prevent this from happening, whereas in DKA the insulin-glucagon balance is shifted in favour of glucagon.
As a result, the Type-1 diabetic DKA patient with zero insulin on board reacts to hyperglycaemia not by quietly dehydrating osmotically over the period of a week, but rather by becoming severely acidotic, and developing unpleasant symptoms which lead them to present early.
In order to qualify as a DKA you must strive towards the following diagnostic criteria:
The clinical features of DKA can be presented in a nice table. And of course, the presence of ketones is the most specific findings. Dont use those nitroprusside sticks, they tend to ignore the presence of β-hydroxybutyrate which is the most prevalent etone in DKA. Rather, go with the finger prick ketones.
Deep Kussmaul breathing
Hypotension due to hypovolemia
Reduced skin turgor and dry mucosa
High anion gap metabolic acidosis
Hyperkalemia (due to acidosis) - but in fact the total body K+ stores are depleted
Anxiety and agitation
Obtundation and coma (if hyperosmolar)
Vomiting and diarrhoea
Exhaled "fruity" odour of ketones
Acute renal failure
These are all features of hyperosmolarity, hypovolemia and metabolic acidosis; both direct effects and compensatory mechanisms.
Having your pH drop to 6.9 is not a consequence-free experience.
Several unpleasant complications may result:
Renal failure as a complication of DKA is generally viewed as a relatively short and uneventful affair. These people come with a history of osmotic diuresis and decreased oral intake, which usually points to hypovolemia as the cause of their kidney injury. Beyond that, there may also be a factor which has contributed to both the DKA and the renal damage - for instance, septic shock or heart failure due to myocardial infarction. However, in spite of this, most of the patients tend to recover their renal function without resorting to dialysis. Orban et al (2014) performed a retrospective review of 94 patients admitted with DKA, and found that though exactly 50% of them had some degree of renal failure (at minimum in the R class of the RIFLE definition) only 3% required CRRT, and in the rest the AKI resolved with only fluid administration (4L on average).
These patients will be between 5 and 10 litres behind in their fluid balance. Generally speaking, about 100ml/kg of water is missing. Oh's Manual suggests that there is no specific difference between the fluid management in DKA and in HONK. They recommend the following fluid resuscitation schedule for both:
With this regimen, for a 70kg DKA/HONK patient, one ends up giving about 1.5-3L in the first 3 hours. There is no reference in The Manual, but closer inspection has revealed that they derive this fluid ressucitation regimen from the Consensus Statement of the American Diabetes Association.
Rationale for fluid resuscitation
Physiological basis for fluid resuscitation with balanced crystalloid
Advantages of saline
Disadvantages of saline
Evidence and opinion in the literature
Several studies are available to guide decision-making, which I will summarise:
If you can do little about the insulin resistance of the stress-response state, at least you can supplement the missing insulin.
How much? Well; it has been demonstrated that a normal low-dose "physiological replacement" infusion works just as well if not better than high dose insulin. That study used a dose rate of 1u/hr, unadjusted to weight. Oh's Manual recommends 0.1u/kg/hr, which would work out to be 7u/hr for a normal sized person. Local policies differ.
The target of therapy is to achieve the following metabolic goals:
Once the BSL is reduced to below 15-12mmol/L, the infusion of insulin can be decreased to more accurately match the patient's requirements - around 0.02-0.05u/Kg/hr, or 1.4-3.5 units per hour.
Table 58.1 on page 631 of the new Ohs Manual presents a list of electrolyte deficits which develop in DKA. There is no reference for this table, but if one digs deep enough one is able to unearth a 2003 article which contains this table within it. I will summarise the relevant features:
Thus, the 70kg DKA patient stands to be infused with up to 7 litres of water, 700mmol of sodium, 350mmol of potassium, 350mmol of chloride, and about 140mmol each of phosphate, magnesium and calcium. In reality, the total infusion requirement may be greater due to diuresis.