Endgames Case Report

An unconscious patient

BMJ 2011; 343 doi: http://dx.doi.org/10.1136/bmj.d7266 (Published 18 November 2011) Cite this as: BMJ 2011;343:d7266
  1. Candice Clarke, core medical trainee,
  2. Elaine Hui, specialist registrar,
  3. Nick Oliver, consultant physician and honorary senior lecturer,
  4. Katie Wynne, senior lecturer and honorary consultant physician
  1. 1Imperial College Healthcare NHS Trust, Hammersmith Hospital, London W12 0NN, UK
  1. Correspondence to: K Wynne k.wynne{at}imperial.ac.uk

A 52 year old woman was found collapsed and unresponsive by her relatives. She was taken by ambulance to the accident and emergency department. On arrival her relatives reported that she was last seen the day before admission, and that she had epilepsy, mild learning difficulties, and type 2 diabetes. Her general practitioner had recently started her on insulin detemir 10 units once daily because of poor glycaemic control. She also took gliclazide 120 mg once daily, metformin 1 g twice daily, pioglitazone 45 mg once daily, phenytoin 100 mg three times daily, and rosuvastatin 20 mg at night. She lived alone in a flat and was independent in all activities of daily living. She had never been admitted to hospital for a complication related to diabetes or epilepsy.

On arrival, her temperature was 32.2°C, blood pressure was 60/30 mm Hg, pulse was 97 beats/min, and her Glasgow coma score was 4/15. Her capillary glucose was beyond the upper limit of the meter and her urinary ketones were negative. Arterial blood gas analysis showed pH 6.85, partial pressure of oxygen 14.2 kPa, partial pressure of carbon dioxide 10.2 kPa, and a base excess of −20.5 mmol/L. Blood tests showed glucose more than 40 mmol/L, lactate 5.1 mmol/L, potassium 2.9 mmol/L, and bicarbonate 8.9 mmol/L. The table shows the patient’s blood test result before her cardiac arrest with reference ranges.

Results of blood tests taken before the patient’s cardiac arrest

View this table:

While in the accident and emergency department, she had a tonic-clonic seizure, followed by an asystolic cardiac arrest. She regained circulation after two cycles of cardiopulmonary resuscitation. She was intubated and transferred to the intensive care unit. On examination she had bibasal chest crepitations. Her cardiovascular and abdominal examinations were normal. A neurological examination was limited because she was sedated, but no focal or upper motor neurone signs were noted.

Her electrocardiograph was normal apart from a sinus tachycardia. Her chest radiograph showed bilateral opacification consistent with consolidation. A computed tomogram of her brain showed a loss of grey white matter differentiation, particularly in the left caudate area, consistent with ischaemic injury.

Questions

  • 1 What is the diagnosis?

  • 2 How should this patient be managed acutely?

  • 3 What insulin regimen should be used?

  • 4 What are the common precipitants of this condition?

Answers

1 What is the diagnosis?

Short answer

This patient has hyperosmolar hyperglycaemic state, previously known as hyperosmolar non-ketotic state. This is one of the most serious acute diabetic complications with a mortality of 10-50%.

Long answer

Hyperosmolar hyperglycaemic state is characterised by marked hyperglycaemia (>33 mmol/L) and raised serum osmolality (>320 mmol/kg).1 Ketoacidosis is usually absent, or less marked than in diabetic ketoacidosis, because sufficient circulating insulin is available to prevent lipolysis, from which ketone bodies are derived. A low bicarbonate value may reflect lactic acidosis rather than diabetic ketoacidosis. Lactic acidosis can occur as a result of poor tissue perfusion in critically ill patients and a further metabolic acidosis may result from acute kidney injury and sepsis. It is important to omit metformin during severe intercurrent illness, particularly in the presence of concurrent kidney injury, because this drug may contribute to lactic acidosis.

This patient had a measured osmolality of 425 mmol/kg and a calculated osmolality of 431 mmol/kg. Serum osmolality is calculated as: Osmc=2×([Na]+[K])+[glucose]+[urea]) mmol/kg. There is an osmolar gap when the calculated serum osmolality is significantly different (>20 mmol/kg) from the osmolality measured by the laboratory. An osmolar gap represents an unmeasured solute, such as ethanol or methanol. In this case the calculated and measured osmolality were similar, suggesting that the hyperosmolality was caused by measured solutes.

2 How should this patient be managed acutely?

Short answer

After initial resuscitation, the remainder of the fluid deficit should be replaced gradually. Frequent clinical assessment and electrolyte monitoring are needed to prevent rapid osmolar shifts.

Long answer

Severe dehydration is common in hyperosmolar hyperglycaemic state. The fluid deficit usually develops gradually over days to weeks and can be more than 8 L. Hyperglycaemia leads to renal loss of water in excess of electrolytes, which results in an increase in plasma sodium concentration. Isotonic saline (0.9% sodium chloride solution) is therefore an appropriate replacement fluid. The patient should be resuscitated with the aim of replacing half of the total water deficit over the first 24 hours. In our patient who had severe hypotension, initial aggressive fluid resuscitation was needed to stabilise blood pressure.

During fluid resuscitation, it is important that the sodium level should fall gradually (by <0.5 mmol/L/h) to minimise the risk of cerebral oedema. Cerebral oedema occurs when rapid falls in osmolality are not matched in the brain and the gradient across the blood-brain barrier causes a shift of free water into the relatively more concentrated brain.

Mild to moderate hyperkalaemia is a common initial finding in hyperosmolar hyperglycaemic state owing to dehydration, renal impairment, and insulin deficiency. Treatment with fluid and insulin will rapidly decrease the serum potassium concentration by shifting potassium from intravascular spaces into cells. Careful monitoring and potassium replacement may be needed to avoid hypokalaemia.

Once capillary blood glucose is <12 mmol/L, a 5% glucose solution can be started with the aim of keeping blood glucose between 13 mmol/L and 16 mmol/L, until the serum osmolality is <320 mmol/kg. A 5% glucose solution is not a substitute for volume replacement, and it may be necessary to continue other fluids.

A hyperosmolar state predisposes to hyperviscosity, and patients are at high risk of both arterial and venous thrombosis. Therapeutic low molecular weight heparin should be started in patients with hyperosmolar hyperglycaemic state unless contraindicated. In patients with an altered level of consciousness, imaging is useful to exclude a concurrent cerebrovascular event before anticoagulation is started.

The lack of clinical research into the treatment of hyperosmolar hyperglycaemic state means that management is largely based on expert opinion.

3 What insulin regimen should be used?

Short answer

Insulin should be administered by continuous intravenous infusion at a low infusion rate to provide a steady and gradual fall in plasma glucose concentrations.2 This approach reduces the risks of hypoglycaemia, hypokalaemia, and cerebral oedema.

Long answer

Hyperosmolar hyperglycaemia is a state of insulin resistance that develops over days or weeks. Hyperglycaemia, like plasma sodium, should be reversed gradually because a rapid drop can lead to cerebral oedema.3 Glucose should be corrected by about 3-4 mmol/L an hour, with infusion rates as low as 0.5-1 U/hour of rapid acting insulin. Measure capillary blood glucose hourly to allow adjustment of the insulin infusion rate. Review the patient’s serum electrolytes, blood glucose values, venous pH, and osmolality every two to four hours to guide ongoing management. As a guide, plasma osmolality should not fall by more than 5 mmol/kg/h.

4 What are the common precipitants of this condition?

Short answer

Infection and myocardial infarction are two major precipitants. In addition, the omission of insulin or the introduction of new drugs, such as corticosteroids, can contribute to hyperglycaemia and lead to this condition.

Long answer

Perform a sepsis screen because infection is a common precipitant of this condition. Urine and blood cultures should be sent urgently before antibiotics are started. An anterior-posterior chest radiograph in this patient showed bilateral opacification consistent with consolidation (fig 1). Antibiotics were started for the treatment of community acquired pneumonia. Hypothermia is a poor prognostic sign and is often associated with sepsis.

Figure1

Fig 1 Anterior-posterior chest radiograph showing bilateral consolidation

An electrocardiograph is essential because acute coronary syndrome can precipitate hyperosmolar hyperglycaemic state. Cardiac enzymes, such as serum troponin, can be mildly raised in any acute severe illness. Measurement of creatine kinase can help detect rhabdomyolysis, which can contribute to acute kidney injury. In one study, 16 of 31 patients presenting with hyperosmolar hyperglycaemic state developed rhabdomyolysis, which is associated with low total body potassium and hypophosphataemia.4

Because our patient presented with reduced consciousness and a seizure, we performed computed tomography of the brain to look for intracranial pathology; this showed hypoxic ischaemic injury (fig 2).

Figure2

Fig 2 Computed tomogram of the brain showing hypoxic ischaemic injury

A full drug history should be sought for any patient presenting with hyperosmolar hyperglycaemic state because the omission or inadequate dosing of insulin is a common cause of this condition. Drugs that affect carbohydrate metabolism such as corticosteroids, thiazides, and second generation antipsychotics have been implicated in the development of hyperglycaemia.

Patient outcome

The patient was fluid resuscitated, given appropriate insulin treatment, and treated for underlying sepsis. She received intensive care for five days and then underwent one month of rehabilitation. She returned to her baseline function and was discharged home with ongoing support from the district nurse. Predictors of mortality in hyperosmolar hyperglycaemic state include older age, presentation with a cardiovascular event, and the presence of other comorbidities.5

Notes

Cite this as: BMJ 2011;343:d7266

Footnotes

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References