HHS: a deadly but neglected complication
Hyperosmolar hyperglycaemic syndrome (HHS) is associated with four- to five-fold higher mortality than diabetic ketoacidosis, yet the condition is still poorly understood. Professors Guillermo Umpierrez and Ketan Dhatariya take a closer look at a complication all too often overlooked by diabetes research.
HHS is a diabetic complication, primarily of type 2 diabetes, that is marked by severe hyperglycaemia and hyperosmolality without the presence of significant ketosis. The condition is characterised by extreme dehydration and, without proper treatment with intravenous saline and insulin, can result in coma, seizures and even death. Yet, as Guillermo and Ketan describe in this latest addition to our ‘The long and the short of it’ series, there is a paucity of prospective randomised studies looking at HHS, with the result that there is a scarcity of data to inform guidelines on its management.
With this neglect in mind, it’s perhaps surprising how long ago the syndrome was first described. As Ketan relates, distinct types of diabetic coma were first noted at end of 19th century. “There was the kind where people wasted away and died very quickly. And the kind, often seen in people who were more overweight, where patients gently slipped into a coma.”
“Over 140 years ago they knew there were two types of diabetic coma,” says Guillermo. “That’s amazing.”
However, it wasn’t until the 1950s, when people could start measuring glucose concentrations and understood osmolalities and basic biochemistry, that HHS was first properly identified. Initially, the state often went by the term ‘HONK’ - hyperglycaemia hyperosmolar nonketotic coma; a misnomer, Ketan points out, given how many people will have HHS without going into a coma.
The 1950s were also the time when John Gerich published the first guidelines on HHS– guidelines which, for lack of appreciable amounts of new data on the subject, have gone pretty much unchallenged since.
So why has it been so neglected? Guillermo thinks this may be due to the fact that DKA is so much more common. That said, he observes, the impact in terms of outcomes is very much worse. “The mortality for HHS is four- to five-fold higher than for DKA. And we treat patients with HHS more or less the same way we treat DKA. I’m really not sure this is the right approach. Something needs to be changed.”
That said, there is crossover between the two. Fascinatingly, as Guillermo points out, 28% of those admitted to his hospital with DKA or HHS in fact have components of both conditions. He cites research showing that those with combined DKA/HHS do worse than those with DKA alone.
Making the diagnoses in the first place and knowing what protocols to follow on diagnosis are, then, absolutely critical, and this film includes detailed advice on the key stages of that process. “If you make the diagnosis,” says Ketan, “then the key thing is fluid replacement. Because these guys are usually really dry. They can be 100-200 ml down per kg compared to people with DKA, who are usually less dehydrated. Only when the glucose stops falling with adequate fluid replacement should you then add in the insulin. But you want to go for gentle osmolality reduction, gentle glucose reduction, because you don’t want huge osmotic shifts, which can lead to central nervous system problems. Plus deal with the underlying precipitating problem – and replace the potassium and electrolytes.”
Such guidance is often more to do with what seems to work rather than an understanding of why it works or what could be done better. As Ketan says: “We need more data on the simple things: which fluid to use? How much to give? What is the rate of insulin we need to give? At the moment, we just pluck numbers out of the air.”
This is a fascinating, wide-ranging discussion, taking in topics as diverse as the history of medicine, COVID-19 and metabolomics. The constant theme, though, is the necessity for more research. Says Guillermo: “I think we need to go back to the basics. What’s the difference between DKA and HHS? Are they two points on the same spectrum? Or do they result from two different pathophysiologies? Collecting samples on admission and during resolution to measure insulin secretion, beta cell function or C-peptide, inflammation or oxidative stress – that’s something we could and should do.”
For more on the topics raised in this discussion, see the following EASD e-Learning courses and presentations:
Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.