A Clinical Review of Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State
Definition
Diabetic Ketoacidosis (DKA) is a life-threatening metabolic emergency defined by the biochemical triad of hyperglycemia (blood glucose >11 mmol/L), ketonemia (blood ketones >3 mmol/L or significant ketonuria), and high anion gap metabolic acidosis (venous pH <7.3 and/or bicarbonate <15 mmol/L) (3). It represents a state of absolute or near-absolute insulin deficiency, leading to a profound catabolic state characterized by the breakdown of fat for energy.
Hyperosmolar Hyperglycemic State (HHS) is a similarly life-threatening metabolic emergency, but it is distinct in its pathophysiology. It is characterized by profound hyperglycemia (typically blood glucose >33.3 mmol/L), severe hyperosmolality (effective serum osmolality >320 mOsm/kg), and significant dehydration, all occurring without significant ketoacidosis (1, 3). This condition arises from a state of relative insulin deficiency, where enough insulin is present to prevent widespread fat breakdown but not enough to control blood sugar. It is crucial to understand that DKA and HHS are not mutually exclusive; a significant number of patients present with a mixed picture, exhibiting features of both severe hyperosmolality and significant ketoacidosis, a scenario that often portends a worse prognosis (7).
Epidemiology
In Malaysia, the management of hyperglycemic crises is a critical and daily clinical skill, a direct consequence of the escalating diabetes epidemic. The 2019 National Health and Morbidity Survey (NHMS) painted a stark picture: a national diabetes prevalence of 18.3% among adults, with the deeply concerning fact that nearly half of these individuals (48.6%) remain undiagnosed (3). This vast, undiagnosed population creates a constant risk pool, where many individuals are "walking time bombs" for a hyperglycemic crisis. For these patients, the dramatic and life-threatening presentation of DKA or HHS is often their first-ever contact with the healthcare system for their diabetes, placing an immense diagnostic and management burden on frontline clinicians in the Emergency Department (4).
While traditional teaching associates DKA with young patients with Type 1 Diabetes Mellitus (T1DM), the Malaysian clinical landscape fundamentally challenges this view. Local research reveals a paradigm-shifting reality: a majority of DKA admissions (over 50%) occur in patients with established Type 2 Diabetes Mellitus (T2DM), often affecting a much older demographic (mean age ~50 years) than seen in Western cohorts (8, 31). This demands a high index of suspicion from every house officer; any patient with T2DM who is unwell is at risk of DKA. Worryingly, the mortality rate for DKA in Malaysian hospitals has been reported to be as high as 17.6%, a figure that is several-fold higher than the <5% rate typically seen in developed nations (20, 31). This suggests potential systemic challenges, including delayed patient presentation, difficulties in early diagnosis at the primary care level, or variations in acute management. The situation in Malaysian children is also concerning, with the rate of DKA at the time of initial T1DM diagnosis remaining stubbornly high, often a consequence of initial misdiagnosis by healthcare providers (34).
Specific epidemiological data for HHS in Malaysia is sparse, a research gap that may reflect under-recognition of the condition. However, global data consistently shows that while HHS is less common than DKA, it carries a significantly higher mortality rate (up to 20%). This is because it typically affects a more vulnerable population: older individuals with T2DM, multiple underlying comorbidities (especially renal and cardiac disease), and often some degree of cognitive or physical impairment that limits their ability to maintain hydration (20).
Etiology
Hyperglycemic crises do not occur in a vacuum. They are almost invariably precipitated by an underlying physiological stressor that disrupts the patient's fragile metabolic balance. A systematic and relentless search for this trigger is a core component of management, as treating the metabolic chaos without addressing its root cause is a recipe for rapid recurrence. The "Five I's" provide a robust framework for considering the common culprits.
Infection: This remains the most frequent precipitant for both DKA and HHS, both globally and within Malaysia, accounting for up to 60% of cases. Pneumonia and urinary tract infections are the most common sites (3, 38). The infectious process unleashes a torrent of pro-inflammatory cytokines and stress hormones, which directly antagonize the action of insulin, driving up glucose production and precipitating the crisis.
Inadequacy (Insulin/Treatment Non-adherence): This is a particularly prominent and challenging issue in the Malaysian context, identified as the single most common trigger for DKA in some local studies, responsible for up to 43.2% of episodes (32). This is rarely a simple case of a patient "forgetting" their insulin. It often reflects a complex interplay of socioeconomic and psychological factors, including the fear of hypoglycemia, the significant financial burden of insulin and monitoring supplies, a lack of understanding regarding the need to increase insulin during illness ("sick day rules"), or co-existing psychological conditions like depression or eating disorders.
Infarction: An acute vascular event, such as a myocardial infarction, stroke, or peripheral arterial occlusion, acts as a profound physiological stressor, triggering a massive counter-regulatory hormone surge that can easily overwhelm the patient's insulin reserves and precipitate a crisis.
Iatrogenic: Medications that alter glucose metabolism are an increasingly recognized cause.
⚠️ SGLT2 Inhibitors (e.g., dapagliflozin, empagliflozin): These drugs represent a major modern diagnostic pitfall. They can cause euglycemic DKA (euDKA), a treacherous condition where life-threatening ketoacidosis develops with only mildly elevated or even normal blood glucose levels. The mechanism involves the drug's primary action of forcing glucose excretion in the urine, which masks the underlying hyperglycemia, while the state of insulin deficiency and physiological stress continues to drive rampant ketogenesis (20). The clinical takeaway is absolute: any patient on an SGLT2 inhibitor who presents with nausea, vomiting, or general malaise must have their ketones checked, regardless of their capillary blood sugar reading.
Other implicated drugs include high-dose corticosteroids, thiazide diuretics, and atypical antipsychotics, all of which can increase insulin resistance or impair insulin secretion.
Intoxication: Alcohol abuse, particularly binge drinking followed by poor oral intake, can precipitate alcoholic ketoacidosis, but can also trigger DKA in patients with diabetes. Other substances of abuse can also act as triggers.
Pathophysiology
DKA and HHS exist on a pathophysiological spectrum of metabolic decompensation, with the primary differentiating factor being the degree of insulin deficiency—absolute versus relative.
The process is initiated by insufficient insulin action, which is then amplified by a surge in counter-regulatory hormones—glucagon, cortisol, catecholamines (epinephrine and norepinephrine), and growth hormone—typically unleashed by a physiological stressor like an infection (1). These hormones work in concert to create a "perfect storm" of hyperglycemia. They dramatically increase hepatic glucose production (by stimulating both glycogenolysis and gluconeogenesis) and simultaneously impair the ability of peripheral tissues like muscle and fat to take up and use glucose, effectively trapping it in the bloodstream (5).
DKA Pathway (Absolute Insulin Deficiency): This is the classic pathway in T1DM or in a patient with T2DM under extreme physiological duress. The complete or near-complete lack of insulin's powerful anti-lipolytic signal means the brakes on fat breakdown are removed. This leads to unopposed lipolysis, flooding the circulation with free fatty acids (FFAs) (2). These FFAs are taken up by the liver where, in the high-glucagon/low-insulin environment, they are shunted into the mitochondrial pathway of β-oxidation. This generates overwhelming amounts of acetyl-CoA, which cannot be processed by the Krebs cycle and is instead diverted into the synthesis of ketoacids: β-hydroxybutyrate and acetoacetate (5). These are strong organic acids. As they accumulate, they release hydrogen ions (H+), which are buffered by the body's bicarbonate system (HCO₃⁻). The relentless consumption of bicarbonate depletes the body's primary alkaline reserve, resulting in a high anion gap metabolic acidosis, the defining biochemical signature of DKA (21).
HHS Pathway (Relative Insulin Deficiency): This pathway is more characteristic of T2DM. In this state, there is still some residual endogenous insulin secretion. This small amount of insulin is often just enough to suppress the rampant, widespread lipolysis required to cause severe ketoacidosis. However, it is completely insufficient to overcome the prevailing insulin resistance and the effects of the counter-regulatory hormone surge, thus failing to control hyperglycemia (2). The result is a vicious, self-perpetuating cycle. The unchecked hyperglycemia leads to blood glucose levels that far exceed the renal threshold for reabsorption (~10 mmol/L), causing a massive osmotic diuresis as glucose spills into the urine, pulling vast quantities of water with it (5). This leads to profound fluid loss—often exceeding 9-10 litres—causing severe intracellular and extracellular dehydration and a marked increase in serum osmolality (24). This severe dehydration reduces intravascular volume, leading to decreased renal perfusion and a fall in the glomerular filtration rate (GFR). The now-impaired kidneys can no longer effectively clear the excess glucose from the blood. This reduced renal clearance causes the blood glucose level to skyrocket even further, which in turn worsens the osmotic diuresis, creating a deadly feedback loop of ever-worsening hyperglycemia, hyperosmolality, and dehydration (5).
Clinical Presentation
Diabetic Ketoacidosis (DKA)
The onset of DKA is characteristically acute and evolves rapidly, often over a period of less than 24 to 48 hours, giving it a dramatic clinical presentation (1).
Diagnostic Clues: The combination of Kussmaul respirations and a sweet, acetone-scented breath is highly specific and should immediately point the clinician towards a diagnosis of ketoacidosis.
Common Symptoms (>50%):
The classic osmotic symptoms of hyperglycemia—polyuria, polydipsia, and nocturia—are early features, often accompanied by profound generalised weakness and fatigue (11).
Gastrointestinal symptoms are extremely common and are a direct result of the ketonemia and acidosis. Nausea and vomiting occur in up to 80% of patients, and diffuse abdominal pain is present in about 30% (1). This abdominal pain can be severe enough, with associated tenderness and guarding, to mimic an acute surgical abdomen like pancreatitis or appendicitis, presenting a major diagnostic challenge. The pain is thought to be caused by delayed gastric emptying and stretching of the liver capsule and is expected to resolve as the metabolic derangements are corrected.
Kussmaul Respirations: This is a pattern of deep, sighing, labored breathing. It is not a sign of primary respiratory distress but is the body's powerful compensatory mechanism to expel carbon dioxide (CO₂), a volatile acid, in an attempt to counteract the severe metabolic acidosis (1).
Acetone Breath: The breakdown of acetoacetate produces acetone, a volatile ketone that is exhaled, giving the breath a characteristic sweet, "fruity" odor, often compared to the smell of pear drops or nail polish remover (1).
Less Common Symptoms (10-50%):
Altered mental status, ranging from mild drowsiness and confusion to stupor or coma, is typically a feature of more severe DKA and correlates with the degree of both acidosis and hyperosmolality (1).
⚠️ Red Flag Signs & Symptoms: Severe abdominal pain mimicking an acute abdomen, any alteration in mental status, or clinical signs of severe dehydration (hypotension, tachycardia, reduced skin turgor).
Hyperosmolar Hyperglycemic State (HHS)
In stark contrast to the rapid onset of DKA, HHS develops insidiously over a period of several days to weeks. This slow evolution allows for the development of far more extreme levels of hyperglycemia and dehydration (1).
Diagnostic Clues: The clinical hallmark of HHS is the presence of severe neurological impairment in the context of extreme hyperglycemia (>33.3 mmol/L) and profound dehydration (12).
Common Symptoms (>50%):
Profound alteration in mental status: This is the most prominent and defining feature. The neurological manifestations are a direct consequence of the severe hyperosmolality causing intracellular dehydration of brain cells. This can range from mild confusion and disorientation to focal neurological deficits (such as hemiparesis, aphasia, or hemianopia, which can perfectly mimic an acute stroke), seizures (focal or generalized), and profound coma (19).
Signs of profound dehydration (e.g., severe orthostatic hypotension, tachycardia, dry and wrinkled mucous membranes, poor skin turgor) are universal and often more severe than in DKA (12).
A preceding history of polyuria, polydipsia, and progressive weakness and lethargy over several days or weeks is typical if a history can be obtained from family (1).
Less Common Symptoms (10-50%):
Gastrointestinal symptoms like nausea and vomiting are much less common and less severe than in DKA. Significant abdominal pain is typically absent (25). Kussmaul respirations are not a feature, as there is no significant acidosis to compensate for.
⚠️ Red Flag Signs & Symptoms: Any focal neurological deficit, seizure activity, or a Glasgow Coma Scale (GCS) score of <12.
Complications
Cerebral Edema: This is a rare but often fatal iatrogenic complication of DKA treatment, occurring more frequently in children and young adults (40). It is thought to be related to overly rapid correction of hyperglycemia and osmolality, causing a fluid shift into the brain. Warning signs include headache, a sudden deterioration in the level of consciousness after initial improvement, bradycardia, and hypertension (Cushing's triad). If suspected, it is a medical emergency requiring immediate action: elevate the head of the bed, restrict intravenous fluids, and administer an osmotic agent like intravenous mannitol or hypertonic saline.
Thromboembolism: The hyperosmolar, hyperviscous state of HHS, combined with immobility, creates a profoundly prothrombotic state. This significantly increases the risk of both venous (deep vein thrombosis, pulmonary embolism) and arterial (myocardial infarction, stroke) thromboembolic events (41).
Hypokalemia & Hypoglycemia: These are the most common iatrogenic complications of treatment and are entirely preventable with diligent, protocol-based monitoring and timely adjustments to insulin and potassium replacement.
Acute Kidney Injury (AKI): Severe dehydration leads to pre-renal AKI in almost all cases. This usually resolves with fluid resuscitation, but persistent AKI may suggest an underlying renal pathology.
Hyperchloremic Metabolic Acidosis: Large-volume resuscitation with 0.9% saline can lead to a non-anion gap metabolic acidosis due to the high chloride load. This is usually clinically benign but can be confusing as it prevents the bicarbonate from normalizing as the ketoacidosis resolves.
Prognosis
The prognosis of a hyperglycemic crisis is heavily influenced by the underlying precipitating illness, the patient's age, the presence of comorbidities, and the severity of the metabolic derangement at presentation (e.g., level of consciousness, degree of acidosis or hyperosmolality). In Malaysia, as noted, DKA carries an unexpectedly high mortality rate of up to 17.6% (31). HHS has an even higher mortality rate globally (5-20%), a stark figure that reflects the older, more frail, and more comorbid patient population it typically affects (20).
Differential Diagnosis
[Alcoholic Ketoacidosis (AKA)]: This is a key differential in a patient with a history of chronic alcohol abuse presenting with a high anion gap metabolic acidosis, often after a period of binge drinking and poor food intake. It is distinguished from DKA by a normal, low, or only mildly elevated blood glucose level. The ratio of β-hydroxybutyrate to acetoacetate is often much higher than in DKA (12).
[Lactic Acidosis]: This should be considered in any patient with metabolic acidosis and signs of circulatory shock (septic, cardiogenic) or tissue hypoperfusion. It is confirmed by a high serum lactate level (>2 mmol/L). While a mild lactic acidosis can co-exist with DKA due to dehydration, a lactate level >5 mmol/L suggests it is the primary or a significant contributor to the acidosis (12).
[Toxic Ingestions]: Ingestion of substances like methanol (found in illicit spirits), ethylene glycol (antifreeze), or salicylates (aspirin overdose) can cause a high anion gap metabolic acidosis. A thorough history from family or paramedics, looking for clues of exposure, and specific toxicological screening are essential if there is any clinical suspicion (12).
[Starvation Ketoacidosis]: This can occur after a period of prolonged fasting. However, the acidosis is usually mild (bicarbonate rarely <18 mmol/L), and the blood glucose is typically low or normal.
Investigations
A structured and timely approach to investigations is essential for confirming the diagnosis, assessing severity, identifying the precipitating cause, and guiding ongoing, dynamic management.
Immediate & Bedside Tests
These are the STAT orders to be performed immediately upon patient arrival in the Emergency Department.
Capillary Blood Glucose: This is the essential first test to rapidly identify hyperglycemia and gauge its severity (4).
Blood/Urine Ketones: A point-of-care blood β-hydroxybutyrate test is the gold standard for diagnosing and monitoring ketosis, as it is quantitative and reflects the true predominant ketoacid (14). If unavailable, a urine ketone dipstick (≥++) is an acceptable alternative per the Malaysian CPG, but the house officer must be aware of its limitations: it primarily detects acetoacetate and can remain positive even when the ketosis is resolving (3).
Venous Blood Gas (VBG): A VBG is sufficient for assessing acid-base status (pH and bicarbonate) in DKA and is safer, less painful, and easier to obtain than an arterial blood gas (ABG). The venous pH is typically only 0.03-0.05 units lower than arterial pH, a clinically insignificant difference for this purpose (16).
Electrocardiogram (ECG): This is mandatory for two critical reasons: to screen for a silent myocardial infarction as a potential trigger, and to look for ECG changes associated with hyperkalemia (peaked T-waves, widened QRS) or hypokalemia (flattened T-waves, presence of U-waves), which can guide urgent and life-saving electrolyte management (3).
Diagnostic Workup
These are the baseline laboratory tests needed for definitive diagnosis and management planning.
First-Line Investigations: A Blood Urea, Serum Electrolytes, and Creatinine (BUSE/RP) panel is the cornerstone of the workup. This is essential to calculate the anion gap and serum osmolality, to assess baseline renal function (which affects fluid and electrolyte management), and, most importantly, to determine the baseline serum potassium level before a single drop of insulin is administered (3).
Gold Standard: The definitive diagnosis is established by the combination of the above tests meeting the specific biochemical criteria for DKA or HHS (1). As mentioned, direct measurement of serum β-hydroxybutyrate (if available) is the gold standard for quantifying ketosis (14).
Critical Calculations:
Anion Gap = [Na⁺] - ([Cl⁻] + [HCO₃⁻]): This is crucial for both diagnosing DKA and tracking its resolution. A closing anion gap is a key therapeutic endpoint.
Effective Serum Osmolality = 2 x [Na⁺] + [Glucose]: This is the defining calculation for diagnosing HHS.
Corrected Sodium: The measured sodium is falsely low in the presence of severe hyperglycemia, which creates an osmotic gradient that pulls water from the intracellular to the extracellular space, diluting the sodium. The corrected sodium must be calculated to accurately assess the patient's true hydration status and to guide the choice of subsequent intravenous fluids (a common formula is to add 1.6 mmol/L to the measured Na⁺ for every 5.6 mmol/L that the serum glucose is above 5.6 mmol/L) (42).
Monitoring & Staging
A diligent search for the precipitating cause must run in parallel with the initial resuscitation efforts.
Full Blood Count (FBC): A high white blood cell count (leukocytosis) with a left shift may suggest an underlying bacterial infection, although it is important to remember that a significant stress-induced leukocytosis is also very common in DKA itself (1).
Urinalysis: To look for evidence of a urinary tract infection (leukocytes, nitrites) (3).
Blood and Urine Cultures: These should be obtained before starting antibiotics if there is any clinical suspicion of infection (e.g., fever, localized signs) (3).
Chest X-ray: To rule out pneumonia, especially if respiratory symptoms are present or if the patient is elderly or has an altered mental state (3).
Management
Patients with severe DKA (e.g., pH <7.1, GCS <12) and all patients with HHS require management in a high-dependency (HDU) or intensive care unit (ICU) where continuous monitoring and rapid therapeutic adjustments are possible (1).
Management Principles
The management of hyperglycemic crises focuses on three simultaneous, interconnected goals: aggressive correction of dehydration to restore circulatory volume, reversal of the underlying catabolic state with insulin, and safe, meticulous restoration of electrolyte balance (especially potassium), all while actively investigating and treating the underlying precipitant (3).
Acute Stabilisation (The First Hour)
Airway/Breathing: Assess and secure the airway. Administer high-flow oxygen via a non-rebreather mask to maintain SpO₂ >94% (the action), which is crucial to prevent tissue hypoxia driven by poor perfusion and altered hemoglobin function (the rationale).
Circulation: This is the immediate priority. Secure two large-bore IV cannulas and administer a stat fluid bolus of IV Normal Saline (0.9% NaCl) 1.0 - 1.5 Litres over the first hour (the action) to rapidly correct hypotension and restore perfusion to vital organs like the brain and kidneys (the rationale) (3). If the patient is in hypotensive shock (systolic BP <90 mmHg), give 500mL boluses rapidly over 10-15 minutes and repeat until the blood pressure stabilizes.
Definitive Therapy
1. Fluid Resuscitation
Subsequent Fluids: The choice of intravenous fluid after the initial bolus is critically guided by the corrected serum sodium. If the corrected Na⁺ is normal or low, it is safe to continue with 0.9% NaCl. However, if the corrected Na⁺ is high, switching to a hypotonic solution like 0.45% NaCl (half-normal saline) is necessary to avoid worsening the hypernatremia and hyperosmolality (1).
Rate: A typical subsequent regimen involves infusing 1 litre over the next 2 hours, followed by 1 litre over the next 4 hours, and then 1 litre over the subsequent 6-8 hours. This rate must be constantly individualized based on the patient's age, hydration status, and cardiovascular and renal function to avoid iatrogenic fluid overload (3).
Adding Dextrose: As the insulin infusion effectively lowers blood glucose, levels will eventually fall. To prevent iatrogenic hypoglycemia while allowing the insulin infusion to continue treating the underlying ketoacidosis (which takes much longer to resolve), intravenous fluids should be switched to a dextrose-containing solution (e.g., 5% or 10% Dextrose in 0.45% NaCl) once the blood glucose level falls to approximately 14 mmol/L (3).
2. Insulin Therapy
⚠️ CRITICAL PREREQUISITE: Do NOT start insulin until the serum potassium is confirmed to be ≥3.3 mmol/L. Insulin works by driving potassium from the bloodstream into the cells. Administering it to a patient who is already hypokalemic can precipitate life-threatening cardiac arrhythmias and cardiac arrest. If the initial potassium is <3.3 mmol/L, insulin must be withheld, and potassium replacement must be started urgently as the first priority (3).
Regimen: The standard of care is a weight-based, fixed-rate intravenous insulin infusion (FRIII). An initial intravenous bolus of insulin is generally no longer recommended, particularly in pediatric populations, as it has not been shown to improve outcomes and may increase the risk of cerebral edema by causing a more rapid fall in osmolality (61).
DKA: Start soluble insulin at a fixed rate of 0.1 units/kg/hour (3).
HHS: A lower starting dose of 0.05 units/kg/hour is recommended. Patients with HHS are often more sensitive to insulin, and the primary goal is a gradual, controlled reduction of osmolality to prevent neurological complications (3).
Transition to Subcutaneous (SC) Insulin: This is a high-risk period for clinical error and rebound ketoacidosis. DKA or HHS is considered biochemically resolved when the criteria are met (pH>7.3, bicarbonate ≥18 mmol/L, and ketones <0.6 mmol/L) and the patient is clinically stable and able to eat and drink. Because intravenous insulin has a very short half-life (minutes), the infusion must not be stopped until a dose of subcutaneous basal (long-acting) insulin has been administered and has had sufficient time to be absorbed. This crucial "overlap" period is essential to prevent a recurrence of ketosis. The subcutaneous basal insulin should be given at least 30-60 minutes before the intravenous infusion is discontinued (1).
3. Electrolyte Management
Potassium Replacement: Meticulous potassium management is a cornerstone of safe DKA/HHS treatment. Despite their initial serum potassium level being normal or even high (due to the extracellular shift caused by acidosis), all patients have a large total body potassium deficit. As treatment with insulin and fluids corrects the acidosis, potassium rapidly shifts back into the cells, leading to a precipitous and dangerous fall in the serum level. Failure to anticipate and proactively replace this potassium can result in severe hypokalemia and fatal cardiac arrhythmias.
If K⁺ is 3.5 - 5.5 mmol/L: Add 20-40 mmol of potassium chloride (KCl) to each litre of IV fluid to maintain the serum K⁺ within this safe range (3).
If K⁺ is <3.5 mmol/L: Withhold insulin. Replace potassium more aggressively (e.g., 20-40 mmol/hr via a central line if necessary) and recheck the level hourly. Only start insulin once the K⁺ is >3.5 mmol/L (3).
If K⁺ is >5.5 mmol/L: Do not add potassium to the initial fluids, but re-check the level every 2 hours as it is guaranteed to fall (3).
Bicarbonate Therapy: The routine use of sodium bicarbonate is strongly NOT recommended in the management of DKA (3). While it may seem logical to treat acidosis with an alkali, bicarbonate therapy has not been shown to improve clinical outcomes and is associated with several potential adverse effects, including worsening intracellular acidosis (paradoxical CNS acidosis), worsening hypokalemia, fluid and sodium overload, and delayed clearance of ketones (68). Its use is restricted only to cases of severe, life-threatening acidosis (arterial pH <6.9) where severe acidemia may be critically compromising myocardial contractility and vascular tone, and even then, it should be used with extreme caution (3).
Supportive & Symptomatic Care
Thrombosis Prophylaxis: All patients with HHS, and most adult patients admitted with DKA (who are often immobilized), should receive prophylactic doses of low-molecular-weight heparin (LMWH) unless there is a clear contraindication, given the high risk of thromboembolic events (41).
Treat the Precipitant: It cannot be overemphasized that mortality in DKA and HHS is often due to the underlying precipitating illness rather than the metabolic derangement itself. A diligent search for and aggressive treatment of the trigger—for example, with empiric broad-spectrum antibiotics for suspected sepsis after cultures have been taken—is a critical and parallel component of management (21).
Key Nursing & Monitoring Instructions
Strict hourly monitoring of capillary blood glucose is mandatory.
Monitor vital signs, Glasgow Coma Scale (GCS), and fluid balance (strict input/output chart) hourly for at least the first 6 hours.
Repeat BUSE/RP and VBG 2-4 hourly to track the response to therapy and guide adjustments.
Inform the medical team immediately of any of the following red flags:
Urine output dropping below <0.5mL/kg/hr.
Systolic BP dropping below 90 mmHg despite initial fluid resuscitation.
Any deterioration in the level of consciousness or new focal neurology.
Long-Term Plan & Patient Education
The successful management of a hyperglycemic crisis does not end when the patient's biochemistry normalizes and they are discharged from the ward. An admission for DKA or HHS represents a catastrophic failure of the patient's outpatient diabetes management and presents a crucial "window of opportunity" to re-educate, re-engage, and implement strategies to prevent recurrence. A well-structured, multidisciplinary discharge plan is as vital as the acute resuscitation.
Patient Education ("Sick Day Rules"): Many hyperglycemic crises are precipitated by an intercurrent illness because patients do not know how to adjust their diabetes management when they are sick. Therefore, intensive patient education on "sick day rules" is a cornerstone of prevention. Every patient with diabetes, particularly those on insulin, should receive clear, simple, written instructions on what to do when they are unwell. Key principles include:
NEVER stop taking insulin or oral diabetes medication. Emphasize that the body needs more insulin during illness, not less, due to stress hormones.
Monitor blood glucose frequently: Check levels every 2-4 hours.
Test for ketones: Check urine or blood for ketones if blood glucose is persistently high (e.g., >14-15 mmol/L).
Maintain hydration: Drink plenty of sugar-free fluids (water, clear soup).
Maintain carbohydrate intake: If unable to eat solid food, consume small, frequent amounts of carbohydrate-containing fluids (e.g., juice, regular soft drinks, soup) to prevent starvation ketosis.
Know when to seek help: Provide clear, explicit criteria for when to contact their doctor or go to the hospital immediately (e.g., persistent vomiting for more than 2 hours, high ketone levels, shortness of breath, or altered mental state).
Structured Discharge Planning: A safe discharge requires a comprehensive, multidisciplinary approach to ensure a smooth transition back to the community and to address the specific factors that led to the admission. This should involve:
Medication Reconciliation and Counseling: The patient's insulin regimen should be reviewed, rationalized, and optimized. The houseman must ensure the patient has a clear, written plan for their new insulin doses, understands how to administer it correctly, and has a reliable supply of insulin and monitoring equipment upon discharge.
Diabetes Education: The inpatient stay should be utilized to provide intensive, one-on-one education, ideally by a dedicated diabetes educator nurse. This should cover all aspects of self-management.
Addressing Root Causes: If non-adherence was the precipitating factor, a non-judgmental inquiry into the underlying reasons must be conducted. This may necessitate referral to a medical social worker to address financial barriers or to a psychologist or counsellor for psychosocial support.
Follow-up: A prompt follow-up appointment should be arranged with the patient's primary care provider or specialist diabetes team, ideally within one to two weeks of discharge. The discharge summary is a critical communication tool and must clearly outline the precipitating factor for the admission, the details of the new management plan, the educational points that were covered, and any outstanding issues that require follow-up.
When to Escalate
A house officer must recognize the limits of their expertise and call for help in a timely manner. Hesitation can be fatal.
Call Your Senior (MO/Specialist) if:
The patient presents with severe DKA (pH <7.1, HCO₃⁻ <5, GCS <12) or any case of HHS from the outset. These patients require immediate senior input and likely ICU admission.
The patient develops any new neurological signs (e.g., headache, confusion) or a drop in GCS during treatment, as this may herald cerebral edema.
The expected biochemical targets are not being met (e.g., ketones are not falling by at least 0.5 mmol/L/hr, or the anion gap is not closing).
The patient develops signs of iatrogenic complications, such as severe fluid overload (pulmonary edema) or severe, difficult-to-manage electrolyte derangements (e.g., K+ <3.0 or >6.0 mmol/L).
The precipitating cause is a severe illness in its own right, such as septic shock or a large myocardial infarction.
Referral Criteria:
Refer to the Nephrology team if acute kidney injury does not resolve with fluid resuscitation.
Refer to the Cardiology team if the precipitant was an acute coronary syndrome or if the patient develops heart failure.
Involve the Diabetes Educator Nurse and Medical Social Worker for all patients admitted with a hyperglycemic crisis before they are discharged. This is not optional; it is a core part of preventing readmission.
References
Kitabchi, A. E., Umpierrez, G. E., Miles, J. M., & Fisher, J. N. (2009). Hyperglycemic crises in adult patients with diabetes. Diabetes Care, 32(7), 1335–1343. https://doi.org/10.2337/dc09-9032
Gosmanov, A. R., Gosmanova, E. O., & Dillard-Cannon, E. (2014). Management of hyperglycemic crises: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. SA-eDUC Journal, 11(1).
Ministry of Health Malaysia. (2020). Clinical Practice Guidelines: Management of Type 2 Diabetes Mellitus (6th Edition). Putrajaya: MOH. https://www.moh.gov.my/moh/resources/Penerbitan/CPG/Endocrine/CPG_T2DM_6th_Edition_2020_13042021.pdf
Royal Australian College of General Practitioners. (2020). Emergency management of hyperglycaemia in primary care. RACGP. https://www.racgp.org.au/getattachment/a56d62af-6c71-4b52-a0a3-70610a0e73ee/Emergency-management-of-hyperglycaemia-in-primary-care.pdf.aspx
Dungan, K. M. (2023). Hyperglycemic Crisis in Adults: Pathophysiology, Presentation, Pitfalls, and Prevention. Clinical Diabetes, 27(1), 19-27.
Umpierrez, G., & Korytkowski, M. (2016). Diabetic emergencies - ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nature Reviews Endocrinology, 12(4), 222–232.
Maletkovic, J., & Drexler, A. (2013). Overlap of diabetic ketoacidosis and hyperosmolar hyperglycemic state. Endocrine Practice, 19(6), 1037-1040.
Ismail, A., & Mohamed, M. (2015). Profiles of Diabetic Ketoacidosis in Multiethnic Diabetic Population of Malaysia. Tropical Journal of Pharmaceutical Research, 14(1), 147-152.
Malaysia Endocrine & Metabolic Society. (2020). Practical Guide to Inpatient Glycaemic Care. MEMS. http://mems.my/wp-content/uploads/2020/07/PRACTICAL-GUIDE-TO-INPATIENT-GLYCAEMIC-CARE_V2-2020.pdf
Ministry of Health Malaysia. (2015). Clinical Practice Guidelines: Management of Type 1 Diabetes in Children and Adolescents. Putrajaya: MOH. https://www.moh.gov.my/moh/resources/Penerbitan/CPG/Endocrine/3a.pdf
Segamat Hospital. (2014). What is diabetic ketoacidosis (DKA)?. JKN Johor. https://jknjohor.moh.gov.my/hsegamat/uploads/penerbitan/buletin/Buletin%202014%20Bil%201%20DKA.pdf
Umpierrez, G. E., & Kitabchi, A. E. (2003). Hyperglycemic Crises. In Endotext. MDText.com, Inc. https://www.ncbi.nlm.nih.gov/books/NBK279052/
Buse, J. B., et al. (2024). Hyperglycemic crises in adults: a consensus report from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 47(1), 1-17.
Cleveland Clinic Journal of Medicine. (2024). Hyperglycemic crises in adults: A look at the 2024 consensus report. Cleveland Clinic Journal of Medicine, 92(3), 152-161. https://www.ccjm.org/content/92/3/152
BMJ Best Practice. (2023). Diabetic ketoacidosis. BMJ Publishing Group.
American Association of Clinical Endocrinology. (2017). Diagnosis and Management of Hyperglycemic Crises. AACE.
Medical News Today. (2023). What is the difference between diabetic ketoacidosis and hyperosmolar hyperglycemic state?.
MIMS Malaysia. (2023). Diabetic Ketoacidosis & Hyperosmolar Hyperglycemic State.
Ministry of Health, Saudi Arabia. (n.d.). DKA/HHS Protocol. https://www.moh.gov.sa/Ministry/MediaCenter/Publications/Documents/Protocol-005.pdf
Dr.Oracle AI. (2024). What are the symptoms of Hyperosmolar Hyperglycemic State (HHS)?.
Ngu, S. H., et al. (2015). Profiles of Diabetic Ketoacidosis in Multiethnic Diabetic Population of Malaysia. ResearchGate. https://www.researchgate.net/publication/279291008_Profiles_of_Diabetic_Ketoacidosis_in_Multiethnic_Diabetic_Population_of_Malaysia
Mohamed, M., et al. (2015). Precipitating factors and outcomes of diabetic ketoacidosis in a Malaysian tertiary care hospital. Tropical Journal of Pharmaceutical Research, 14(1), 147-152.
Lee, W. Y., et al. (2024). Predictors and Trends of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes Mellitus in Malaysian Children. Journal of Clinical Research in Pediatric Endocrinology, 16(1), 411-418. https://jcrpe.org/articles/predictors-and-trends-of-diabetic-ketoacidosis-at-diagnosis-of-type-1-diabetes-mellitus-in-malaysian-children/jcrpe.galenos.2024.2024-1-8
Pasquel, F. J., & Umpierrez, G. E. (2014). Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care, 37(11), 3124–3131.
Mayo Clinic. (2023). Diabetic ketoacidosis.
MSD Manual Professional Edition. (2023). Hyperosmolar Hyperglycemic State (HHS). https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hyperosmolar-hyperglycemic-state-hhs
Merck Manuals Professional Edition. (2023). Diabetic Ketoacidosis (DKA). https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetic-ketoacidosis-dka
The Association of British Clinical Diabetologists. (2023). The Management of Diabetic Ketoacidosis in Adults. ABCD. https://abcd.care/sites/default/files/site_uploads/JBDS_Guidelines_Current/JBDS_02_DKA_Guideline_with_QR_code_March_2023.pdf
LITFL. (2020). Sodium Bicarbonate and Diabetic Ketoacidosis. https://litfl.com/sodium-bicarbonate-and-diabetic-ketoacidosis/
