Diabetic emergencies represent acute, life-threatening complications requiring immediate medical intervention (Khan and Salman, 2024). Among these, diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are particularly critical conditions encountered in patients with diabetes (Dhatariya et al, 2020a; National Institute for Health and Care Excellence (NICE), 2024a).
DKA is characterised by a triad of hyperglycaemia, ketonaemia, and metabolic acidosis (Singh et al, 2023). Notably, euglycaemic DKA can occur, presenting with normal blood glucose levels, particularly in pregnancy or in patients using sodium-glucose co-transporter 2 (SGLT2) inhibitors (such as ‘flozins’), which lower blood glucose by promoting glycosuria (Morace et al, 2024; Scottish Intercollegiate Guidelines Network, 2024).
HHS, on the other hand, is defined by severe hyperglycaemia, elevated serum osmolality, and significant dehydration (Lim and Taylor, 2024). Whereas DKA and HHS are often considered distinct entities, their clinical presentations can sometimes overlap, complicating diagnosis and management.
This review aims to guide advanced clinical practitioners (ACPs) on how to recognise and treat DKA and HHS. The article provides an overview of the role of ACPs in the management of DKA and HHS. It will explore the epidemiology, pathophysiology, clinical presentations, diagnostic criteria, and management strategies for these critical diabetic emergencies. The ultimate goal is to enhance clinical practice, support ACPs in their roles, and improve patient outcomes by ensuring timely and effective treatment of DKA and HHS. The UK diagnostics criteria of DKA and HHS are summarised in Table 1.
| DKA – all 3 of | HHS – characteristic features |
|---|---|
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Serum osmolality = 2[Na+] + glucose + urea
Source: adapted from Joint British Diabetes Societies for Impatient Care, 2023; BMJ Best Practice, 2024a
Epidemiology of DKA and HHS
In the UK, DKA is a significant concern, particularly among young adults aged 18 to 24 years, where the incidence is highest (Joint British Diabetes Societies for Inpatient Care, 2023). The frequency of DKA in individuals with type 1 diabetes varies widely, ranging from 8.0 to 51.3 cases per 1000 patient-years (Joint British Diabetes Societies for Inpatient Care, 2023). DKA is also a costly condition to manage, with the estimated cost of treating a single episode being £2064 for adults and £1387 for those aged 11 to 18 years (Allcock et al, 2022). Although the mortality rate from DKA in the UK remains below 1%, it is the leading cause of death among people under 58 years with type 1 diabetes (Dhatariya and Joint British Diabetes Societies for Inpatient Care, 2022). The risk of mortality increases with age and the presence of pre-existing comorbidities.
HHS is a relatively rare but severe complication of diabetes, with an estimated prevalence of less than 1% of all diabetesrelated hospital admissions (Mekala and Bertoni, 2020). The incidence rate is approximately 17.5 per 100000 patient-years (Huang et al, 2023). The mortality rate for HHS can reach up to 20%, which is approximately 10 times higher than the mortality rate associated with DKA (Mohajan and Mohajan, 2023). The complexity involved in determining precise figures is due to the lack of comprehensive population-based studies and the multiple comorbidities often present in these patients.
The role of ACPs in treating DKA and HHS
ACPs are highly skilled health professionals who have undergone advanced training to expand their scope of practice beyond the traditional roles of nurses, paramedics, or other allied health professionals (Health Education England (HEE), 2017). ACPs are typically trained at Master's level and acquire the competencies across four pillars of advanced practice: clinical practice, leadership and management, research and education to perform clinical assessment, diagnosis, and the initiation and management of treatment plans (HEE, 2022). They work autonomously within multidisciplinary teams and are capable of making complex clinical decisions to improve patient outcomes within their scope of practice (Alsararatee, 2024).
Identification and initial management
The ACP might be the first health professional to evaluate patients presenting with symptoms of DKA and HHS (HEE, 2022). Their advanced clinical skills enable them to promptly identify these conditions through detailed patient assessments and interpretation of diagnostic tests, such as blood glucose levels, serum ketones, and blood gases. Early identification is crucial for initiating life-saving treatments (Barnard, 2019).
Treatment and monitoring
ACPs are responsible for managing the acute phases of DKA and HHS. This includes initiating fluid resuscitation, insulin therapy, and electrolyte replacement, as well as continuously monitoring the patient's response to treatment (HEE, 2022). ACPs are skilled in adjusting therapeutic interventions based on the patient's evolving condition, which is essential for preventing complications such as cerebral oedema in DKA or thrombosis in HHS.
Co-ordination of care
As key members of the multidisciplinary team, ACPs coordinate with other specialists, such as diabetes specialist nurses, endocrinologists, nephrologists, and intensive care teams, to ensure comprehensive care. They play a pivotal role in communicating the patient's condition and progress to the team, facilitating collaborative decision-making, and ensuring that all aspects of the patient's care are addressed (HEE, 2017).
Patient education and prevention
Beyond acute treatment, ACPs are instrumental in educating patients about managing their diabetes, particularly during periods of illness or stress, which can precipitate DKA or HHS. They provide guidance on medication adherence, dietary considerations, and recognising early warning signs, thereby helping to prevent future episodes and reduce the likelihood of hospital readmissions. Diabetes specialist nurses (DSNs) play a critical role in managing DKA and HHS by providing expert care, patient education, and supporting ACPs in treatment plans. They help patients manage their condition, particularly in monitoring blood glucose and preventing complications (Dhatariya et al, 2020b).
Pathogenesis
Insulin is essential for survival, as it facilitates the cellular uptake of glucose for energy, reduces glucose production by the liver, and promotes the storage of glucose in muscles and fat (Chandrasekaran and Weiskirchen, 2024). Both DKA and HHS arise due to deficiencies in insulin, either absolute or relative, accompanied by an increase in counter-regulatory hormones (Mungai et al, 2024). In DKA, an absolute deficiency of insulin, often triggered by a stressor, leads to increased gluconeogenesis and glycogenolysis (Newland-Jones et al, 2024). This exacerbates hyperglycaemia since cells cannot absorb glucose in the absence of insulin (Curran, 2018). Consequently, the lack of insulin activates hormone-sensitive lipase in adipose tissue, leading to the breakdown of fat and the production of ketone bodies through fatty acid oxidation (Aramovna et al, 2023). These ketoacids are toxic by-products, and their accumulation results in metabolic acidosis (Elendu et al, 2023). The combination of hyperglycaemia and hyperketonaemia induces osmotic diuresis, causing significant fluid loss and electrolyte imbalances, including sodium, potassium, and chloride depletion (Newland-Jones et al, 2024). In HHS, the relative insulin deficiency leads to a more pronounced osmotic diuresis, causing more severe dehydration than in DKA, and typically occurs without significant ketone accumulation (Mustafa et al, 2023).
Causes of DKA and HHS
Several factors and situations can predispose individuals to the development of DKA and HHS as explained in Table 2.
| Causes of DKA | Causes of HHS |
|---|---|
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Source: adapted from Patel, 2021
Clinical assessment of patients with DKA or HHS
DKA can affect individuals across all age groups, making patient age at presentation less relevant (Kamrath et al, 2024). The condition typically develops over a period of hours to days. Although some patients may seek medical advice upon detecting hyperglycaemia or elevated ketones through their own monitoring devices, this is not always the case. Common presenting symptoms, along with their underlying pathophysiological causes and associated signs, are summarised in Table 3. It is important to note that these clinical features are non-specific, necessitating high clinical vigilance for accurate diagnosis and timely intervention. Table 3 explains the signs and symptoms the ACP might encounter with DKA.
| Signs and symptoms | Description | Commonality |
|---|---|---|
| Nausea and/or vomiting | DKA is suspected in patients with presenting with nausea and/or vomiting who have known diabetes, often accompanied by increased thirst, frequent urination, unexplained weight loss, or extreme tiredness | Common |
| Abdominal pain | Abdominal examination is crucial to rule out underlying causes of DKA, such as pancreatitis; DKA may present similarly to an acute abdomen. Therefore clinicians should rule out DKA before surgery | Common |
| Dehydration | Check for signs of dehydration, which include dry mucous membranes, reduced skin elasticity, delayed capillary refill, rapid heartbeat with a weak pulse, and low blood pressure | Common |
| Hyperventilation | This late sign involves deep, sighing breaths and may indicate severe acidosis; occurs at a slow or normal respiratory rate | Common |
| Reduced consciousness | Consciousness should be assessed hourly; a decline in mental status is associated with severe DKA and a worse prognosis, potentially leading to cerebral oedema | Common |
| Acetone smell on breath | The breath may have a scent resembling pear drops or nail varnish remover, due to elevated ketone levels | Common |
| Hypothermia | Severe cases of hypothermia carry a high mortality risk; mild hypothermia may occur due to peripheral vasodilation | Uncommon |
Source: adapted from BMJ Best Practice, 2024b; NICE, 2024b
When DKA is suspected it is crucial to use the ‘ABCDE’ assessment to determine the severity of the patient's condition and guide appropriate treatment plans (Woolfe Loftus et al, 2024). This systematic approach helps identify and address immediate life-threatening problems, ensuring comprehensive and prioritised care to stabilise the patient effectively. In addition, using the Early Warning Score (EWS) can assist in continuously monitoring the patient's condition, facilitating early detection of deterioration and timely intervention (Woolfe Loftus et al, 2024). Furthermore, ACPs should be aware of the EWS points; for instance, a patient might score 2 for their respiratory rate, which may not seem critical. However, their rapid, deep breathing might be related to severe metabolic acidosis, as the patient tries to blow off acidic carbon dioxide to increase blood pH. Therefore, recognising these signs within the EWS framework is essential for timely and appropriate intervention.
ACPs should also be aware that a reduced level of consciousness may be due to extreme hyperglycaemia (blood glucose >30mmol/litre) (Gordon, 2023). Appropriate inspection of the patient's body is essential, including the removal of any bandages or dressings, as this can uncover sources of sepsis, such as an infected foot ulcer. Recognising these signs within the EWS framework is essential for timely and appropriate intervention.
Although HHS typically affects older patients, it can occur in younger patients too, due to the use of high-dose corticosteroids and the increasing prevalence of type 2 diabetes in this population (Gosmanov et al, 2021). HHS usually develops over several days, with patients often presenting in a severely dehydrated state, exhibiting drowsiness or stupor (Orłowska et al, 2024). Obtaining a collateral history (from a family member, friend or carer) is often necessary to assist the ACP in their assessment.
Investigations and diagnosis of DKA and HHS
The investigation process for DKA and HHS is crucial for accurate diagnosis and effective management. Both conditions require a comprehensive set of investigations to assess the severity and underlying causes. Hyperglycaemia may be confirmed with a venous gas analyser or laboratory blood glucose test, noting that euglycaemic DKA should be considered in specific scenarios such as in patients on SGLT2 inhibitors (Davies et al, 2022).
Measurement of ketones, either in blood or urine, is essential to confirm ketonaemia in DKA (Curran, 2018). A biochemical profile is essential to evaluate electrolyte imbalances, renal function, and the extent of metabolic derangement (Calimag et al, 2023). Venous blood gases are used to assess metabolic acidosis in DKA, while arterial blood gases may be necessary if an additional condition requires the measurement of partial pressure of oxygen (Millner and Devlin, 2023).
In HHS, metabolic acidosis is less common, but blood gases can help assess the patient's overall metabolic state (Umpierrez et al, 2024). Serum osmolality should also be measured, particularly in HHS, to evaluate the degree of hyperosmolality (Mustafa et al, 2023). A full blood count is important to detect infection, or other haematological abnormalities. Microbiological cultures, including blood and urine cultures, are conducted to identify potential sources of infection, with sensitivities guiding appropriate antibiotic therapy if an infection is detected (Joint British Diabetes Societies for Inpatient Care, 2023). Imaging and cardiac assessments, such as chest X-rays and electrocardiograms (ECG), are performed to identify respiratory infections, thoracic conditions, or arrhythmias, particularly if electrolyte imbalances are present (Joint British Diabetes Societies for Inpatient Care, 2023). Infection screening and cardiac markers such as troponin may be indicated to assess for myocardial infarction or other cardiac events (Xu et al, 2024). Moreover, cardiac monitoring might be required if there are significant hypoglycaemia or hyperglycaemia (Curran, 2018).
By performing these investigations, ACPs and doctors can accurately diagnose DKA or HHS, determine the severity of the condition, and identify any precipitating factors or complications, ensuring timely and appropriate treatment to improve patient outcomes and reduce the risk of further complications.
DKA management
It is important to note that local trust guidelines must be followed, as treatments may vary slightly. However, the main goals of DKA management are fluid and electrolyte replacement, insulin replacement, and close monitoring.
Fluids and electrolytes replacement
It is vital to restore circulating volume using intravenous normal saline. The amount of fluid is calculated based on the patient's weight (Joint British Diabetes Societies for Inpaient Care, 2023). If the patient becomes hypotensive, additional fluids are required. Moreover, the patient should have an immediate review by senior colleagues and the ACP should consider involving critical care staff if there is no improvement after administering the fluids.
As blood glucose levels approach normal, it is important to switch to glucose-based fluids to provide a substrate for insulin and prevent hypoglycaemia (Vanderpant et al, 2024). Potassium supplementation may be necessary if hypokalaemia is present (Besen et al, 2023). Caution should be taken with the rate of fluid replacement, especially in young individuals (due to the risk of cerebral oedema) and those with active cardiac, renal, or hepatic problems (Kostopoulou et al, 2023).
Insulin replacements
Intravenous insulin should be administered, usually 50 units of an insulin such as Actrapid, starting at a fixed rate of 0.1units/kg/hour (Joint British Diabetes Societies for Inpatient Care, 2023). It is recommended to continue the patient's usual subcutaneous long-acting (basal) insulin at the usual dose, if the patient takes it (Joint British Diabetes Societies for Inpatient Care, 2023). This ensures that, once the patient recovers from DKA, the transition from intravenous to subcutaneous insulin is smoother and the length of hospital stay is reduced, as the basal insulin is already active (Joint British Diabetes Societies for Inpatient Care, 2023). Moreover, since the serum half-life of rapid-acting insulin in infusions is only a few minutes, there is a risk of rebound ketosis if the infusion is interrupted. This risk is minimised if basal insulin is maintained.
HHS management
In HHS management, it is important to gradually restore circulating volume, starting with intravenous normal saline (Fajardo, 2020). If plasma glucose concentration or osmolality plateaus, switching to 0.45% normal saline may be necessary. As with DKA, caution with fluid replacement is needed in patients with active renal, cardiac or hepatic issues. Additional glucose-based intravenous fluids may be required as blood glucose levels approach normal to prevent hypoglycaemia (Diabetes UK, 2024).
Plasma hyperosmolality and hyperglycaemia should be reduced initially through fluid replacement (Umpierrez, 2020). Unlike in DKA, intravenous insulin should be started concurrently only if hyperketonaemia (indicating lipolysis) is present or if blood glucose concentrations begin to plateau. Close, regular monitoring of plasma osmolality, glucose and electrolytes is essential.
Resolution of HHS may take up to 72 hours and is influenced by the patient's comorbidities and the underlying cause (Patel, 2021). The patient's level of consciousness should improve, alongside reductions in plasma glucose concentration and osmolality (Victor et al, 2022). Intravenous treatment can be discontinued once the patient is able to eat and drink, and when appropriate glucose-lowering therapies are initiated or resumed as necessary.
Minimising the risk of DKA and HHS recurrence
It is essential to identify any contributing factors to the episode of DKA or HHS. If mental health concerns are suspected, such as intentional insulin omission for self-harm, overdose, or eating disorders, or if there are alcohol-related issues, appropriate support services should be engaged. A thorough patient assessment by the hospital's diabetes team before discharge is highly recommended (Farhood and Abdulwahhab, 2024). This allows for a review of the patient's current diabetes management and treatment plans (including the continued use of SGLT2 inhibitors), the provision of additional monitoring tools if necessary, and the reinforcement of ‘sick day rules’ (such as the importance of continuing basal insulin for those with type 1 diabetes). Educational resources and care plans should also be made available to families and carers, with specialist follow-up arranged as needed. These actions can help to prevent future episodes and reduce the likelihood of readmission.