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Diabetes and endocrine emergencies 

Diabetes and endocrine emergencies
Chapter:
Diabetes and endocrine emergencies
Author(s):

Punit S. Ramrakha

, Kevin P. Moore

, and Amir H. Sam

DOI:
10.1093/med/9780198797425.003.0009
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date: 11 August 2020

Diabetic ketoacidosis: assessment

DKA predominantly occurs in patients with type 1 diabetes mellitus (T1DM) and insulin-dependent type 2 diabetes mellitus (T2DM). It is also being increasingly recognized in the initial presentation of an atypical form of T2DM in non-white patients known as ketosis-prone T2DM where there is a severe, transient defect in insulin secretion.

Clinical features

These include:

  • Polyuria and polydipsia; patients become dehydrated over a few days.

  • Weight loss, weakness.

  • Hyperventilation or breathlessness; the acidosis causes Kussmaul’s respiration (a deep sighing respiration).

  • Abdominal pain: DKA may present as an ‘acute abdomen’.

  • Vomiting: exacerbates dehydration.

  • Confusion, coma occurs in 10%.

  • On examination, pay attention to the haemodynamic stability, state of hydration, ventilation rate, level of consciousness, and septic foci.

Investigations

  • Blood glucose

Assess capillary and venous blood glucose. This need not be very high (≥11mmol/L) (see ‘Note’ below).

  • Venous gas

Assess the degree of acidosis (see ‘Note’ below).

  • U&E, Mg2+

Assess serum K+ and renal function.

Corrected Na+ = Na+ + 1.6 × [(plasma glucose − 55)/5.5]

Serum osmolality = 2 × (Na+) + urea + glucose

  • Urinalysis

Ketones strongly positive (≥2+) (see ‘Note’ below).

  • Urinary HCG

Exclude pregnancy in ♀ of childbearing potential.

  • FBC

WBC may be elevated (neutrophilia): a leukaemoid reaction can occur in absence of infection.

  • Septic screen

Urine and blood cultures.

  • Plasma ketones

Ketones elevated (≥3mmol/L) (see ‘Note’ below).

  • CXR

Look specifically for any infection.

  • Amylase

May be high, with abdominal pain and vomiting, in absence of pancreatitis. Acute pancreatitis may occur in 7–10% of patients with DKA (often in association with hypertriglyceridaemia).

Note

  • Diagnosis of DKA requires all three of:

    • Blood glucose ≥11mmol/L.

    • Ketonaemia ≥3mmol/L (≥2+ on urinalysis).

    • Metabolic acidosis with venous or arterial pH ≤7.30 and/or serum bicarbonate ≤15mmol/L.

  • Consider hyperosmolar hyperglycaemic syndrome (HHS) (Diabetes and endocrine emergencies Hyperosmolar hyperglycaemic syndrome, pp. [link][link]) and other causes of hyperglycaemia/acidosis, e.g. aspirin OD and lactic acidosis.

  • Severe acidaemia can be present with glucose values as low as 11mmol/L if the patient has recently taken insulin (as this alone is insufficient to correct the acidosis in the presence of dehydration) or is managed using an SC insulin pump (where ketosis can develop rapidly if infusion of insulin via the insulin pump fails).

  • Plasma ketones should be measured using bedside ketone meters, if available.

  • Ketones may be present in normal individuals after a period of starvation.

  • False-positive ketones on urinalysis can occur with certain drugs (e.g. levodopa, phenazopyrazine, valproic acid, vitamin C). If in doubt, assess plasma ketones.

  • Venous blood gas is sufficient, unless clinical need to monitor pO2/pCO2 level in patients.

Common precipitants of DKA

  • Infections: 30%.

  • Non-compliance with treatment: 20%.

  • Newly diagnosed DM: 25%.

  • Surgical abdomen/pancreatitis: 10%.

Poor prognostic features in DKA

Consider HDU management, central venous access, excluding a surgical cause, and early liaison with ITU when:

  • Oxygen saturations <92%.

  • SBP <90mmHg, or pulse >100 or <60bpm.

  • GCS score <12.

  • Oliguria.

  • pH <7.0 or serum bicarbonate <5mmol/L or ketones >6mmol/L.

  • Hypokalaemia on admission (K+ <3.5mmol/L).

  • Lactate >6.

  • Anion gap >16.

  • Serum osmolality >320.

  • Significant comorbidities, e.g. cardiac failure, renal failure.

  • Worsening acidosis/ketonaemia despite treatment.

DKA: management

General measures

  • Initiate rehydration and fixed-dose IV insulin therapy without delay.

  • Site two IV cannulae: one in each arm (one for 0.9% saline and one for insulin ± glucose). Start fluid replacement (see Diabetes and endocrine emergencies Fluid replacement, p. [link]).

  • Consider a central line in patients with poor prognostic features.

  • NBM for at least 6h (gastroparesis is common).

  • NG tube: if there is impaired conscious level, to prevent vomiting and aspiration.

  • Urinary catheter if oliguria is present or serum creatinine is high.

  • Broad-spectrum antibiotics if infection suspected.

  • Prophylactic-dose LMWH should be given unless contraindicated.

  • Some patients may require monitoring on an ECG for T-wave changes during treatment.

  • Monitor blood glucose, capillary ketones, and urine output hourly.

  • Venous blood gas (pH, bicarbonate K+) at 0, 4, 6, 12, and 18h and before stopping the fixed-rate insulin regimen.

  • U&Es at 0, 6, 12, and 24h (Mg2+ levels should be monitored daily).

Fluid replacement

Use normal (0.9%) saline to replace the fluid deficit. The average fluid loss in DKA is 100mL/kg. (More cautious fluid replacement is needed for patients with cardiac and renal disease, elderly patients, young patients aged 18–25 years, and pregnant patients.)

  • 1L of 0.9% saline over 1h*.

  • 1L of 0.9% saline over 2h × 2*.

  • 1L of 0.9% saline over 4h × 2*.

  • 1L of 0.9% saline over 6h.*.

  • If SBP <90mmHg, give 500mL of 0.9% saline IV over 15–20min. Repeat further if SBP <100mmHg. If poor response, consider septic shock or cardiac failure. Central venous monitoring needed to guide further fluid management.

  • When blood glucose reaches ≤14mmol/L, IV 10% glucose is given at 125mL/h concurrently with 0.9% saline (through an IV cannula in the other arm). Consider reducing 0.9% saline infusion if risk of overload.

  • Use of bicarbonate is not recommended routinely.

Potassium replacement

Total body K+ is depleted, and plasma K+ level falls rapidly as K+ shifts into cells under the action of insulin. Do not give potassium chloride (KCl) in the first litre or if serum K+ is >5.5mmol/L. All subsequent fluid for the next 24h should contain KCl, unless the urine output is <30mL/h or serum K+ remains in excess of 5.5mmol/L (see Table 9.1).

Table 9.1 Suggested regimen for potassium supplementation

Plasma K+ (mmol/L)

Amount of K+ (mmol) to add to each litre of fluid

>5.50

Nil

3.5–5.5

40

<3.5

Seek advice from senior or specialist*

* Additional K+ may be needed (e.g. 40mmol in 100mL of 0.9% saline over 2h) via a central line in HDU.

Insulin replacement

The only indication for delaying insulin is a serum K+ level of <3.3mmol/L, as insulin will worsen hypokalaemia by driving K+ into cells. Patients with an initial serum K+ level of <3.3mmol/L should receive fluid and K+ replacement prior to insulin.

  • Start an IV insulin infusion with 50U of soluble insulin added to 50mL of 0.9% saline delivered via a syringe driver.

  • High-dose fixed-rate IV insulin is infused at 0.1U/kg/h, e.g. for an 80-kg man, give 8U/h until exit criteria (see Diabetes and endocrine emergencies Exit criteria and cessation of IV insulin, p. [link]).

  • SC basal (long-acting) insulin should be continued at the usual dose, alongside the high-dose fixed-rate IV insulin infusion.

  • The response to insulin infusion is reviewed after 1h. If blood glucose is not dropping by 3mmol/h and capillary ketones by 0.5mmol/L, the infusion rate is Diabetes and endocrine emergencies by 1U/h. The increase in insulin infusion rate may be repeated hourly, if necessary, to achieve a reduction in blood glucose and capillary ketones. Urinary ketones may take a little longer to clear.

Exit criteria and cessation of IV insulin

  • The fixed-rate insulin is continued until capillary ketones are <0.6mmol/L and venous bicarbonate is >15. At this point, if the patient is eating and drinking regularly, stop the IV insulin pump 30–60min after rapid-acting insulin with meal.

  • SC basal insulin should have been continued on admission, but if stopped in error, give prior to discontinuing IV insulin as the half-life of IV insulin is short and continued replacement (IV or SC) is essential.

  • If the patient is not eating and drinking or if severe sepsis or ACS, change to variable-rate insulin infusion (see Table 9.2).

  • Ensure a review by the specialist diabetes team has taken place within 24h of admission.

Table 9.2 Example of variable-rate insulin infusion prescription

Blood glucose (hourly) (mmol/L)

Insulin infusion (U/h)

<4.0

0.5

4.1–7.0

1

7.1–9.0

2

9.1–11.0

3

11.1–14.0

4

14.1–17

5

17.1–20

6

>20.0

6—call doctor

DKA: targets and complications

Biochemical targets

Remember, rapid normalization of biochemistry can be detrimental in any patient. It is wiser to be cautious and suboptimal than enthusiastic and dangerous.

  • Reduce capillary blood glucose by 3mmol/L per hour.

  • Increase venous bicarbonate by 3mmol/L per hour.

  • Reduce plasma ketone concentration by 0.5mmol/L per hour.

Complications

(See Box 9.1.)

  • Avoid hypoglycaemia or hypokalaemia from overzealous insulin replacement.

  • Cerebral oedema occurs mainly in children. It may be precipitated by sudden shifts in plasma osmolality during treatment. Symptoms include drowsiness, severe headache, confusion. Treat as described under Diabetes and endocrine emergencies Raised intracranial pressure, pp. [link][link]. Give IV mannitol 0.5g/kg body weight, repeated as necessary. Restrict IV fluids and move to ITU. Mortality is 70%; recovery of normal function is only 7–14%.

  • Serum PO43– falls during treatment, as it moves intracellularly with K+. PO43– levels do not need to be routinely monitored, but consider assessment in presence of respiratory or skeletal weakness. If the PO43– level is <0.3mmol/L, give PO43– IV (monobasic potassium phosphate infused at a maximum rate of 9mmol every 12h). Check preparations with your pharmacy. Monitor Ca2+ levels during the infusion.

  • Serum Mg2+ may fall during insulin therapy. If Mg2+ levels fall to <0.5mmol/L, give 4–8mmol (2mL of 50%) magnesium sulfate over 15–30min in 50mL of normal saline. Repeat as necessary.

  • Hyperchloraemic acidosis (normal anion gap acidosis in a well-hydrated patient) may be seen with excessive administration of saline and in consumption of bicarbonate. No specific treatment is required.

  • Tissue hypoperfusion results from dehydration and may trigger the coagulation cascade and result in thromboembolism. Use LWMH (e.g. enoxaparin SC) for prophylaxis.

DKA: management key points

(See Box 9.2.)

Further reading

Joint British Diabetes Societies Inpatient Care Group (2013). The management of diabetic ketoacidosis in adults, 2nd edn. Diabetes and endocrine emergencies https://www.diabetes.org.uk/resources-s3/2017-09/Management-of-DKA-241013.pdf

Hyperosmolar hyperglycaemic syndrome (HHS) 1

HHS (previously known as hyperosmolar non-ketotic coma or HONK) classically occurs in elderly patients with T2DM. With a rise in early-onset T2DM, it is now appearing increasingly in younger patients. Complications from vascular thromboembolism and cerebral oedema are common. Reported mortality is as high as 33%.

Presentation

  • Often occurs in the elderly, frequently with multiple comorbidities.

  • Onset over many days with preceding polyuria, polydipsia, and symptoms from a precipitating cause (e.g. infection).

  • Severe dehydration.

  • Impaired conscious level: the degree correlates most with plasma osmolality. Coma is usually associated with an osmolality of >440.

  • The patient may present with a stroke, seizures, or MI.

Characteristic features

  • Marked hyperglycaemia (30mmol/L or more).

  • Without significant hyperketonaemia (<3mmol/L) or acidosis (pH >7.3, bicarbonate >15mmol/L).

  • Osmolality 320mOsm/kg or more.

  • Hypovolaemia.

Precipitants

  • Infection—thorough physical examination is important.

  • MI or CVA.

  • GI bleed.

  • Poor compliance with oral antidiabetic agents or high-sugar diet.

  • Self-neglect or elder abuse.

  • Drugs: steroids, diuretics, β‎-blockers, antihistamines.

Investigations

  • Glucose: usually very high (≥30mmol/L).

  • U&Es: dehydration causes a greater rise in urea than creatinine (normal ratio of creatinine:urea up to 20:1 micromol/L:mmol/L).

  • Significant hypernatraemia: may be masked by high glucose. Hypernatraemia may appear to worsen as glucose falls.

  • ABG: usually pH >7.3, serum bicarbonate ≥15mmol/L. Coexisting lactic acidosis considerably worsens the prognosis.

  • Plasma osmolality: calculated by: [2 × (Na+) + urea + glucose]; >320mOsm/kg for diagnosis. Useful indicator of severity and for monitoring response to treatment.

  • FBC: polycythaemia and leucocytosis may indicate dehydration or infection, respectively.

  • ECG: look for MI or ischaemia.

  • CXR: look for signs of infection.

  • Urine: for urinalysis, ketones, and MC&S.

  • Plasma ketones: may occur due to poor intake, but the level is usually <4mmol/L.

  • CT/MRI brain: consider stroke or cerebral infection as a precipitant.

Management: general measures

The goals are to normalize plasma osmolality and blood glucose, to replace fluid and electrolyte losses, and to prevent complications.

  • Manage in well-staffed acute medical unit (AMU) or HDU/ITU if concerning features.

  • Rehydration is the mainstay of treatment. Cautious in the elderly.

  • May need CVP monitoring to guide rehydration.

  • NBM for at least 6h, and insert an NG tube in patients with impaired conscious level to prevent vomiting and aspiration.

  • Urinary catheter if there is oliguria or high serum creatinine.

  • Prophylactic-dose LMWH should be given unless contraindicated. Full-dose anticoagulation if ACS/VTE suspected.

  • Treatment of sepsis or precipitating factors.

  • High risk of feet ulceration. Examine the feet daily, and use heel protection if reduced consciousness or uncooperative.

  • Monitor blood glucose, U&Es, plasma osmolality, and urine output hourly for the first 6h and 2-hourly thereafter if response satisfactory.

  • Continuous pulse oximetry, and consider cardiac monitoring in high-risk patients.

Fluid replacement

The average fluid lost is 8–10L. This should be replaced cautiously over 48h, especially as most patients are elderly. Remember that 0.9% normal saline is hypotonic, relative to the patient’s serum, and is therefore the fluid of choice, even with hypernatraemia.

  • Aim for positive balance of 3–6L by 12h. Longer if comorbidities.

  • If in doubt, replace fluid cautiously. Over-correction can lead to fluid overload, cerebral oedema, and central pontine myelinolysis.

  • 1L of normal saline over the first 60min, then:

  • 1L of normal saline with K+ (see Table 9.1) every 2h × 2, then:

  • 1L of normal saline with K+ (see Table 9.1) every 6h until rehydrated (~48h).

  • Monitor plasma osmolality. Best indicator of rate of change of hyperosmolar state to treatment.

  • As hyperglycaemia is treated, an initial rise in Na+ is expected. This is not an indication for hypotonic fluid. A rise in Na+ is only a concern if plasma osmolality is not decreasing.

NB ‘Corrected’ serum Na+ = measured serum Na+ + [the increment above normal in blood glucose (in mmol/L)/2.3].

  • Use 0.45% normal saline only if plasma osmolality not decreasing despite positive balance.

  • Aim for rate of fall in plasma Na+ of <10mmol/L in 24h.

HHS 2

Blood glucose and insulin

Aim for a fall in blood glucose of <5mmol/h. Reducing the serum glucose level acutely to below 14mmol/L may promote the development of cerebral oedema. Patients with HHS tend to be more sensitive to the effects of insulin.

  • Do not start insulin, unless significant ketonaemia is present. Use low-dose IV insulin (0.05U/kg/h) only if ketonaemia (urine >2+ or plasma >1) or if blood glucose not falling with rehydration alone.

  • Increase insulin by 1U/h if there is no fall in glucose.

  • If blood glucose <14mmol/L, commence 5% or 10% glucose infusion at 125mL/h concurrently with normal saline; stop IV insulin, and continue to monitor blood glucose.

  • If the patient is eating and drinking regularly, stop IV insulin; continue rehydration, and consider starting SC insulin with target glucose of 10–15mmol/L. If previously on oral agents, restart on advice from the specialist diabetes team.

Poor prognostic features in HHS

Consider HDU/ITU management:

  • Serum oxygen saturations <92%.

  • SBP <90.

  • Pulse >100 or <60bpm.

  • GCS score <12.

  • Oliguria.

  • Hypothermia.

  • K+ <3.5mmol/L or >6mmol/L.

  • Lactate >6.

  • pH <7.0.

  • Anion gap >16.

  • Plasma osmolality >350.

  • Plasma Na+ >160.

  • CVA or ACS.

  • Significant comorbidities, e.g. cardiac or renal failure.

HHS: management key points

(See Box 9.3.)

Further reading

Joint British Diabetes Societies Inpatient Care Group (2012). The management of hyperosmolar hyperglycaemic state (HHS) in adults with diabetes. Diabetes and endocrine emergencies http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_HHS_Adults.pdf

Hypoglycaemia: assessment

  • All unconscious patients should be assumed to be hypoglycaemic until proven otherwise. Always check a blood glucose using a bedside blood glucose meter immediately, and confirm with a lab glucose.

  • Almost 8% of adult inpatients experience hypoglycaemia. The most common cause of coma in a patient with DM is hypoglycaemia due to insulin or sulfonylureas.

  • Patients who are not known to have DM should have laboratory blood glucose, and insulin and C-peptide determination (for insulinoma or factitious drug administration) before glucose treatment.

Presentation

Sympathetic overactivity (glucose <3.6mmol/L)

  • Tachycardia.

  • Palpitations.

  • Sweating.

  • Anxiety.

  • Pallor.

  • Tremor.

  • Cold extremities.

Neuroglycopenia (glucose <2.6mmol/L)

  • Confusion.

  • Slurred speech.

  • Focal neurological defect (stroke-like syndromes).

  • Coma.

  • Patients with well-controlled DM have more frequent episodes of hypoglycaemia and can become desensitized to sympathetic activation. These patients may develop neuroglycopenia before sympathetic activation and complain of ‘loss of warning’ (hypoglycaemic unawareness).

  • β‎-blockers blunt the symptoms of sympathetic activation, and patients taking these drugs lose the early warning of hypoglycaemia.

  • Patients with poorly controlled DM develop sympathetic signs early and avoid these by running a high blood glucose. They may complain of having a ‘hypo’ when their blood sugar is normal or high. They do not require glucose treatment. Re-education and gradual improvement of glucose control may be needed.

  • Patients who have type 1 or pancreatic diabetes for a longer duration may have more frequent and severe episodes of hypoglycaemia.

Investigations

  • Blood glucose (bedside glucose meter must be confirmed by lab glucose for a new admission or hypoglycaemic coma).

  • For patients not known to have DM, take blood (clotted, heparin, and fluoride oxalate tubes) prior to giving glucose, for insulin and C-peptide levels (send blood to the lab on ice for immediate centrifugation).

  • Other investigations depend on the presentation (new admission vs inpatients) and cause (dictated by history and medications) (see Box 9.4).

Note

  • A lab glucose of <2.2mmol/L is defined as a severe attack.

  • Coma usually occurs with blood glucose <1.5mmol/L.

  • Low C-peptide and high insulin levels indicate exogenous insulin; high C-peptide and insulin levels indicate endogenous insulin, e.g. surreptitious drug (sulfonylurea) ingestion or insulinoma.

Causes of hypoglycaemia

In the majority of inpatients with DM, hypoglycaemia occurs due to:

  • Diabetes and endocrine emergencies insulin and sulfonylureas:

    • Prescription errors such as wrong insulin, dose, or time.

    • Inappropriate use of drugs or insulins.

    • Sliding scale.

  • Diabetes and endocrine emergencies insulin or medication requirements:

    • Acute illness, e.g. sepsis, renal or liver failure.

    • Drugs, e.g. reduction in steroids.

    • Reduced oral intake or change in dietary pattern.

Other causes are summarized in Box 9.4 and should be considered in any new presentation or recurrent causes of hypoglycaemia.

Hypoglycaemia: management

Acute measures

(See Box 9.5.)

  • Remember to take blood prior to glucose administration (glucose, insulin, C-peptide) (Diabetes and endocrine emergencies Hypoglycaemia: assessment, pp. [link][link]).

  • If there is a history of chronic alcohol intake or malnourishment, give IV thiamine 1–2mg/kg to avoid precipitating WE.

  • Mild (patient conscious, orientated, and able to swallow):

    • If the patient is conscious and cooperative, give 15–20g of quick-acting carbohydrate (see Box 9.5). Test glucose after 10–15min; if <4mmol/L, repeat treatment up to three times.*

  • Moderate (patient conscious, but confused/disorientated or aggressive, and able to swallow):

    • If cooperative and safe to swallow, treat as for mild hypoglycaemia; otherwise give either 1.5–2 tubes of Glucogel® squeezed into the mouth between the teeth and gums or treat as for severe hypoglycaemia. Test glucose after 10–15min; if <4mmol/L, repeat treatment up to three times.*

  • Severe (patient unconscious, fitting, or aggressive):

    • 80mL of 20% glucose IV over 10min (or 160mL of 10% glucose IV over 10min); 50% glucose IV is not advised.

    • If IV access is difficult, give 1mg of glucagon IM. Glucagon is not effective if recurrent hypos, liver disease, starved, or NBM and can only be used once. Test glucose after 10–15min. It should be >4mmol/L.*

Hypoglycaemia: further management

Further management

  • Review glucose regularly in all patients. Give hypoglycaemia education, and refer to the diabetes specialist nurse (DSN) if diabetic.

  • Patients should regain consciousness or become coherent within 10min, although complete cognitive/neurological recovery may lag by 30–45min. Do not give further boluses of IV glucose without repeating the blood glucose. If the patient does not wake up after ~10min, repeat the blood glucose and consider another cause of coma (e.g. head injury while hypoglycaemic; Diabetes and endocrine emergencies Head injury: presentation, p. [link]).

  • Prolonged severe hypoglycaemia (>4h) may result in permanent cerebral dysfunction.

  • Patients on sulfonylureas may become hypoglycaemic following a CVA or other illness preventing adequate food intake.

  • Recurrent hypoglycaemia may herald the onset of diabetic nephropathy, as this decreases insulin requirements—insulin is partly degraded by the kidney and sulfonylureas are really excreted.

  • Review the patient’s current medication, and inspect all tablets from home.

  • Admit if risk of recurrent hypoglycaemia, e.g. with OD of long-acting insulin or sulfonylurea. Observe with hourly blood glucose and 10% IV glucose at 125mL/h.

  • Consider psychiatric review if self-inflicted.

  • Two episodes of hypoglycaemia requiring emergency (third-party) assistance requires Driver and Vehicle Licensing Authority (DVLA) notification [one episode if category C (heavy goods vehicle, HGV) licence].

For key points in the management of hypoglycaemia, see Box 9.6.

Further reading

Joint British Diabetes Societies for Inpatient Care (2018). The hospital management of hypoglycaemia in adults with diabetes mellitus, 3rd edn. Diabetes and endocrine emergencies https://diabetes-resources-production.s3.eu-west-1.amazonaws.com/resources-s3/2018-05/JBDS_HypoGuidelineRevised2.pdf%2008.05.18.pdf

Urgent surgery or procedures in patients with diabetes

Surgery and certain procedures require patients to fast for several hours. In addition, general anaesthesia and surgery produce significant stresses on an individual. The hormonal response to stress involves a significant rise in counter-regulatory hormones to insulin, in particular cortisol and adrenaline. For this reason, patients with DM undergoing surgery will still need insulin despite their fasting state.

Current guidelines for elective procedures advise regular glucose monitoring and avoiding variable-rate insulin infusion (sliding scale), wherever possible, with earlier planned procedures. In most cases of urgent surgery or procedures, patients may need insulin infusion as they may be acutely unwell. If >1 missed meal or ketones >3, variable-rate insulin infusion is needed. Aim for blood glucose of 6–10mmol/L. Give 0.45% saline with 5% glucose and 0.15% or 0.3% KCl as maintenance fluid with the insulin infusion. Continue long-acting analogues, and discontinue insulin infusion after the first meal with short-acting insulin or the usual medications. Surgery in patients with HHS or DKA should be avoided unless life-threatening emergency.

Further reading

Joint British Diabetes Societies for Inpatient Care (2016). Management of adults with diabetes undergoing surgery and elective procedures: improving standards, revised March 2016. Diabetes and endocrine emergencies https://www.diabetes.org.uk/resources-s3/2017-09/Surgical%20guidelines%202015%20-%20full%20FINAL%20amended%20Mar%202016_0.pdf

Diabetic foot complications

While in hospital, 2.2% of patients will develop a diabetic foot complication. A foot problem should be excluded in all patients with DM. All patients admitted with DM should have a thorough foot examination (inspect for any ulceration and deformity, inspect footwear, palpate foot pulses, and test sensation). Complications, including any new ulcer, swelling, discoloration, infection, hot area, blisters, deformity, pain, and cold or pale feet, should be managed with prompt referral to a multidisciplinary footcare team (see Box 9.7).

Further reading

National Institute for Health and Care Excellence (2016). Diabetic foot problems: prevention and management. NICE guideline [NG19]. Diabetes and endocrine emergencies https://www.nice.org.uk/guidance/NG19

Hyponatraemia: assessment

Presentation

  • Mild hyponatraemia (Na+ 130–135mmol/L) is common, especially in patients taking thiazide diuretics and is usually asymptomatic. Moderate hyponatraemia (Na+ 120–129mmol/L) is usually asymptomatic, unless it has developed rapidly.

  • Severe hyponatraemia (Na+ <120mmol/L) may be associated with disturbed mental state, restlessness, headache, confusion, irritability, and nausea and vomiting. Severe symptoms, such as seizures, GCS scores <8 or coma, and cardiorespiratory compromise, prevail as Na+ acutely (<24h) drops below 115mmol/L.

History

History should focus on drugs, fluid losses (diarrhoea, frequency, sweating), alcohol misuse, symptoms of cortisol deficiency, and symptoms or history of thyroid, cardiac, lung, liver, or renal disease.

Examination

Examination should focus on careful assessment of volume status and, in particular, should assess whether the patient is hypovolaemic, normovolaemic, or overloaded/oedematous. Patients should therefore have an assessment of their lying and standing BP, HR, JVP or CVP, skin turgor, and the presence of oedema or ascites.

Patients who are hyponatraemic and hypovolaemic are salt-depleted.

Investigations

  • In addition to U&Es, other tests should be aimed at excluding other causes of hyponatraemia (Diabetes and endocrine emergencies Hyponatraemia: causes, pp. [link][link]).

Common initial tests include:

  • Measurement of serum osmolarity and its comparison to the calculated osmolarity [2 × (Na+ + K+) + urea + glucose]. An increase in osmolar gap is seen with substances such as ethylene glycol, severe hyperglycaemia, mannitol, etc.

  • Spot urine Na+ estimation, combined with clinical assessment of fluid status, may help determine the underlying cause:

    • Volume depletion from an extrarenal cause (Diabetes and endocrine emergencies Hyponatraemia: causes, pp. [link][link]) is normally associated with a low urinary Na+ (<10mmol/L).

    • Volume depletion with a high urinary Na+ (>20mmol/L) suggests inappropriate renal salt-wasting (e.g. intrinsic renal disease, hypothyroidism, adrenal insufficiency, diuretics).

    • Fluid overload with a low urinary Na+ (<10mmol/L) is seen in conditions such as CCF, cirrhosis, or nephrotic syndrome where there is Na+ retention in response to poor renal perfusion.

    • Euvolaemia with high urinary Na+ is seen with SIADH and rarely with severe myxoedema.

General principles

  • Assessment of the patient’s volume status (neck veins, orthostatic hypotension, cardiac signs of fluid overload, ascites, skin turgor) will help in both diagnosis and subsequent treatment.

  • Mild asymptomatic hyponatraemia will usually respond to treatment of the underlying cause, and no specific therapy is necessary.

  • Correction of hyponatraemia should be gradual to avoid volume overload and/or central pontine myelinolysis. Aim to restore serum Na+ to ~125mmol/L actively, and allow to rise gradually after that by treating the underlying cause.

  • Chronic hyponatraemia (>48h) can be corrected gradually. Significant acute (<24h) hyponatraemia (>10mmol/L decline in serum Na+ or Na+ <120mmol/L) and severe symptomatic hyponatraemia require more aggressive correction and monitoring. Seek expert help (see Box 9.8).

  • Patients with cirrhosis and ascites and severe hyponatraemia should have diuretics stopped, as diuretics worsen any reduction in tissue perfusion and therefore reduce the ability to excrete free water.

  • SIADH or other conditions associated with plasma volume expansion can cause hypouricaemia (Diabetes and endocrine emergencies renal clearance). Urate levels can therefore be useful in differentiating hyponatraemia due to SIADH from other causes of low Na+.

Hyponatraemia: causes

Decreased serum osmolarity

Hypovolaemia (hyponatraemia + hypovolaemia = salt depletion)

Renal losses (urinary Na+ >20mmol/L)

  • Diuretics.

  • Addison’s disease.

  • Na+-losing nephropathies.

  • Cerebral salt wasting.

Non-renal losses (urinary Na+ <20mmol/L)

  • GI losses (diarrhoea, vomiting).

  • Burns.

  • Fluid sequestration (e.g. peritonitis, pancreatitis).

Normovolaemia (normal or mildly increased extracellular volume)

SIADH: urine osmolarity >100, serum osmolarity low (<280), urine Na+ >30mmol/L.

CNS disorders

  • Trauma.

  • Stroke/SAH.

  • Malignancy (primary/secondary).

  • Vasculitis (e.g. SLE).

  • Infection (abscess or meningoencephalitis).

Malignancy

  • Lung (oat cell).

  • Pancreas.

  • Lymphoma or leukaemia.

  • Prostate.

  • Urinary tract.

  • Head and neck carcinoma.

Pulmonary disease

  • Pneumonia.

  • TB.

  • Lung abscess.

  • Cystic fibrosis.

  • Lung vasculitis.

Drugs

(via SIADH ± Diabetes and endocrine emergencies renal sensitivity to ADH or Na+ > water loss)

  • Opiates.

  • Haloperidol.

  • Amitriptyline.

  • Cyclophosphamide.

  • Vasopressin.

  • Thioridazine.

  • Carbamazepine.

  • Clofibrate.

  • Oxytocin.

  • Chlorpropamide.

  • Thiazides.

  • Vincristine.

Miscellaneous causes

  • Severe myxoedema.

  • Alcohol misuse.

  • Psychogenic polydipsia.

Oedematous states

  • CCF.

  • Severe renal failure.

  • Cirrhosis with ascites.

  • Nephrotic syndrome.

Normal serum osmolarity

  • Pseudohyponatraemia or ‘redistributive hyponatraemia’ (e.g. lipaemic serum, paraprotein >10g/dL).

  • Intracellular shift of Na+ (e.g. hyperglycaemia, ethylene glycol).

Hyponatraemia: management

  • Exclude pseudohyponatraemia: lipaemic serum will be obvious (ask the biochemist). Calculate the osmolar gap to check there are no ‘hidden’ osmoles (Diabetes and endocrine emergencies Hyponatraemia: causes, pp. [link][link]). Always exclude the possibility of artefactual Na+ from blood taken proximal to an IVI.

  • The correction in Na+ concentration must not exceed 10mmol/L in the first 24h and 8mmol/L per day thereafter. Rapid correction of hyponatraemia must be avoided, as it can result in osmotic demyelination known as ‘cerebral pontine myelinolysis’ (see Box 9.9).

  • Chronic hyponatraemia can be corrected gradually.

  • Symptomatic hyponatraemia (e.g. seizures or coma): requires a more aggressive initial correction to increase serum Na+ concentration (see Box 9.10). Seek expert help early.

  • If volume-deplete (dehydrated): start an IVI of normal saline (0.9% = 154mmol/L of Na+); insert a central venous line if indicated. Monitor fluid output. Catheterize the bladder if there is renal impairment. Watch out for heart failure.

  • If not dehydrated: for patients with moderate SIADH, restrict fluid intake to 500–1000mL/24h. Seek expert help.

  • Remember that giving K+ can raise plasma Na+ levels in a hyponatraemic subject. The increase in Na+ concentration caused by concurrent K+ administration should be taken into account to avoid over-rapid correction of hyponatraemia. Any K+ added to the infused solution should be considered as Na+ in the equation below (see Box 9.10), i.e.: change in [Na+] = {fluid [Na+ + fluid [K+]} − serum [Na+]/(total body water + 1).

* Preferably via a central line in an HDU setting. If hypertonic (3%) saline is not available, discuss alternatives with your pharmacist (e.g. 250mL of hypertonic 1.8% saline).

Further reading

National Institute for Health and Care Excellence CKS (2015). Hyponatraemia. Diabetes and endocrine emergencies http://cks.nice.org.uk/hyponatraemia

Spasovski G, Vanholder R, Allolio B, et al.; Hyponatraemia Guideline Development Group. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014;170:G1–47. Diabetes and endocrine emergencies http://www.eje-online.org/content/170/3/G1.full.Find this resource:

Hypernatraemia

Abnormalities in serum Na+ are usually associated with changes in serum osmolality and extracellular volume (ECV).

Presentation

Symptoms often relate to severe volume depletion: weakness, malaise, fatigue, altered mental status, confusion, delirium, or coma.

Many patients with severe hypernatraemia are seen in intensive care, often with an intracranial catastrophe. The cause or mechanism of hypernatraemia in these patients is unknown.

Causes

  • Osmotic diuresis (glycosuria), as seen in HHS.

  • Critically ill with intracranial pathology.

  • Diarrhoea/protracted vomiting.

  • Burns.

  • Diabetes insipidus (DI) (particularly when the patient becomes unwell and is unable to keep up with oral fluids).

  • Respiratory losses (hot, dry environment).

  • Iatrogenic (administration of salt/saline or sodium bicarbonate).

  • Mineralocorticoid excess (Conn’s, Cushing’s).

The way to determine the cause of abnormal serum Na+ is by:

  • Careful assessment of the ECV [evaluation of neck veins, supine and standing BP, any cardiac signs of fluid overload (e.g. S3, oedema), and skin turgor], in association with:

  • Measuring serum and urine osmolality. Serum osmolality may be estimated by [2 × (Na+ + K+) + urea + glucose], but this is inaccurate when there are other osmoles (e.g. ketones, ethanol, methanol, ethylene glycol, renal failure) that contribute.

Serum Na+ >145mmol/L is always associated with hyperosmolarity.

Management

  • Avoid rapid and extreme changes in serum Na+ concentration. It is safer to change serum Na+ cautiously. Aim initially for no more than 10mmol reduction in 24h.

  • If there is hypovolaemia, start fluid replacement. Normal saline (0.9%) contains elemental Na+ at 154mmol/L. Use this initially to correct hypovolaemia, if present, then change to 5% glucose to replace water and slowly correct Na+ concentration.

  • If the patient is haemodynamically stable, encourage oral fluids.

  • Monitor electrolytes twice daily initially, and more frequently if hypernatraemia is known to be acute (<48h).

Acute hypocalcaemia

Presentation

  • Abnormal neurological sensations and neuromuscular excitability.

  • Numbness around the mouth and paraesthesiae of the distal limbs.

  • Hyper-reflexia.

  • Carpopedal spasm.

  • Tetanic contractions (may include laryngospasm).

  • Focal or generalized seizures. Rarely extrapyramidal signs or papilloedema.

  • Hypotension, bradycardia, arrhythmias, and CCF.

  • Chvostek’s sign is elicited by tapping the facial nerve just anterior to the ear, causing contraction of the facial muscles (seen in 10% of normals).

  • Trousseau’s sign is elicited by inflating a BP cuff for 3–5min 10–20mmHg above the level of SBP. This causes mild ischaemia and unmasks latent neuromuscular hyperexcitability, and carpal spasm is observed. (Carpopedal spasm may also occur during hyperventilation-induced respiratory alkalosis.)

Investigations

  • Plasma Ca2+, PO43–, and albumin.

  • Corrected Ca2+ = measured Ca2+ + [40 − serum albumin (g/L)] × 0.02.

  • Plasma Mg2+.

  • Vitamin D and ALP.

  • U&Es.

  • ECG (prolonged QT interval).

  • Plasma PTH level.

  • Skull X-ray (SXR) (intracranial calcification, especially hypoparathyroidism).

Management

  • The aim of acute management is to ameliorate the acute manifestations of hypocalcaemia, and not necessarily to return Ca2+ to normal.

  • For frank tetany, 10mL of 10% calcium gluconate (diluted in 100mL of normal saline or 5% glucose) can be given by slow IV injection over 10min. NB: 10mL of 10% calcium chloride (9mmol) contains ~4-fold more Ca2+ than calcium gluconate. Calcium gluconate is preferred, as it causes less tissue necrosis if it extravasates. IV Ca2+ should never be given faster than this because of the risk of arrhythmia. This initial treatment with IV calcium gluconate is followed with a slow infusion of calcium gluconate—add 100mL of 10% calcium gluconate to 1L of normal saline or 5% glucose. Start the infusion at 50mL/h, and titrate to maintain serum Ca2+ in the low-normal range.

  • Post-parathyroidectomy, mild hypocalcaemia normally ensues, requiring observation only. In patients who have parathyroid bone disease, however, ‘hungry bones’ may cause profound hypocalcaemia shortly after the parathyroids are removed. This may cause severe and prolonged hypocalcaemia which requires prolonged treatment.

  • Chronic hypocalcaemia is best managed with oral Ca2+, together with either vitamin D or, if the cause is hypoparathyroidism or an abnormality in vitamin D metabolism, a form of hydroxylated vitamin D such as alfacalcidol or calcitriol.

  • If Mg2+ deficiency is present, add 20mL (~40mmol) of 50% magnesium sulfate solution to 230mL of normal saline (10g/250mL). Infuse 50mL of this (equivalent to 2g of magnesium sulfate, 8 mmol) over 10min, and at 25mL/h thereafter.

For causes of hypocalcaemia, see Box 9.11. For key points on the management of hypocalcaemia, see Box 9.12.

Hypercalcaemia

Definition

  • Mild—corrected Ca2+ 2.65–3mmol/L.

  • Moderate—corrected Ca2+ 3.01–3.40mmol/L.

  • Severe—>3.4mmol/L.

  • The free (ionic) plasma Ca2+ concentration is dependent on both arterial pH (increases with acidaemia due to Diabetes and endocrine emergencies protein binding of ionized Ca2+) and plasma albumin.

  • Corrected Ca2+ = measured Ca2+ + [40 − serum albumin (g/L)] × 0.02; for example, if measured Ca2+ = 2.10mmol/L and albumin = 30g/L, corrected Ca2+ = 2.10 = [(40 − 30) × 0.02] = 2.30mmol/L.

  • Most blood gas analysers now measure ionized Ca2+.

For causes of hypercalcaemia, see Box 9.13.

Presentation

  • Routine biochemical screen in an asymptomatic patient.

  • General: symptoms are often non-specific and include depression (30–40%), weakness (30%), tiredness and malaise, itching, keratitis, and corneal calcification.

  • GI: constipation, anorexia, vague abdominal symptoms (nausea, vomiting), weight loss.

  • Renal: renal calculi (if long-standing); nephrogenic DI (20%); type 1 renal tubular acidosis; pre-renal failure; chronic hypercalcaemic nephropathy, polyuria, polydipsia, or dehydration.

  • Neuropsychiatric: anxiety, depression, and cognitive dysfunction; coma or obtundation.

  • Cardiac: hypertension, cardiac dysrhythmias, short QT interval on ECG.

For investigations of hypercalcaemia, see Box 9.14.

Urgent treatment is required if

  • Ca2+ >3.4mmol/L or if symptomatic, i.e.:

    • Clouding of consciousness or confusion is present.

    • Hypotension.

    • Severe dehydration causing pre-renal failure.

Management

  • Rehydrate patient with IV 0.9% saline. Aim for about 3–6L/24h, depending on fluid status (CVP), urine output, and cardiac function.

  • If the patient does not pass urine for 4h, pass a urinary catheter and a central venous line to monitor CVP.

  • Stop medications which may be contributing to hypercalcaemia, i.e. thiazide diuretics.

  • Diuretics: once the patient is rehydrated, continue 0.9% saline infusion and consider adding furosemide with care. Avoid further dehydration, and carefully monitor K+ and other electrolytes and replace if necessary. The usual dose is 20mg every 4h (i.e. with each litre); however, some patients may need a larger dose to avoid pulmonary oedema. Patients need to have K+ added to all the bags to avoid hypokalaemia with this protocol. In large doses (in combination with large amounts of 0.9% saline), furosemide can help increase Ca2+ excretion, although there is some lack of evidence of the efficacy of this approach. Continue monitoring CVP carefully to prevent either fluid overload or dehydration.

  • Monitor electrolytes, especially K+ and Mg2+ which may fall rapidly with rehydration and furosemide. Replace K+ (20–40mmol/L of saline) and Mg2+ (up to 2mmol/L saline) IV.

  • If this fails to reduce plasma Ca2+ adequately (Ca2+ still >2.8mmol/L), then the following measures should be considered:

    • Bisphosphonates: inhibit osteoclast activity, thereby causing a fall in plasma Ca2+. Administer pamidronate at 30–60mg IV over 4–6h. (As a general rule, give 30mg over 4h if Ca2+ is <3mmol/L or for all patients with significant renal impairment, 60mg over 8h if Ca2+ is 3–4 mmol/L.) Ca2+ levels begin to fall after 48h and remain suppressed for up to 14 days. Zoledronic acid has a shorter infusion time (15min) and is said to more effective with a longer duration of action.

  • Salmon calcitonin 400IU q8h. This has a rapid onset of action (within hours), but its effect lasts only 2–3 days (tachyphylaxis). It may also provoke nausea.

  • Steroids (prednisolone 30–60mg PO od): most effective in hypercalcaemia due to sarcoidosis, myeloma, or vitamin D intoxication.

  • Consider use of the calcimimetic ‘cinacalcet’ if hypercalcaemia is due to primary hyperparathyroidism not amenable to surgical treatment.

  • Familial hypocalciuric hypercalcaemia: elevated Ca2+, normal 24h urinary Ca2+. This causes few symptoms (mild fatigue or lethargy). PTH may be raised, but the patient does not respond to parathyroidectomy.

  • Dialysis may be considered in refractive hypercalcaemia or if large fluid loads are not feasible.

For key points in the management of hypercalcaemia, see Box 9.15.

Further reading

National Institute for Health and Care Excellence CKS (2014). Hypercalcaemia. Diabetes and endocrine emergencies http://cks.nice.org.uk/hypercalcaemia

Hypophosphataemia

Plasma PO43– is normally 0.8–1.4mmol/L. Hypophosphataemia is common and often unrecognized by clinicians. Most intracellular PO43– is present as creatine phosphate or adenine phosphates [e.g. adenosine triphosphate (ATP)], and in RBCs, the predominant species is 2,3-diphosphoglycerate. Hypophosphataemia does not necessarily indicate PO43– deficiency; similarly, PO43– deficiency may be associated with normal or high plasma PO43– concentrations. See Box 9.16 for causes of hypophosphataemia.

Presentation

  • Most cases of severe hypophosphataemia occur in very sick patients (often in an ITU). Occasionally seen in asymptomatic patients.

  • Coincident Mg2+ deficiency exacerbates PO43– depletion, and vice versa.

  • Modest hypophosphataemia has no effect but warrants investigation. Severe hypophosphataemia (<0.4mmol/L) may cause symptoms and requires treatment.

See Box 9.17 for manifestations of severe hypophosphataemia.

Investigations

  • Vitamin D and PTH.

  • LFTs.

  • Aldosterone.

  • ABGs.

  • Serum glucose.

  • Serum and urine electrophoresis.

  • 24h urine PO43–.

Treatment

  • PO43– repletion should generally be reserved for patients with sustained hypophosphataemia (e.g. ≤0.4mmol/L). Treatment of the underlying cause (DKA, diarrhoea, vitamin D deficiency) will often correct hypophosphataemia.

  • Orally, give effervescent Phosphate Sandoz® two tablets tds or potassium phosphate IV (9–18mmol/24h).

  • IV PO43– replacement can be considered in severe deficiency but should be used with care. Aggressive IV PO43– therapy can cause hypocalcaemia with seizures and tetany, as well as renal impairment and potentially arrhythmias. Serum PO43– and Ca2+ levels should be monitored 6-hourly during PO43– infusion.

  • Excessive PO43– replacement may cause hypocalcaemia and metastatic calcification; monitor Ca2+, PO43–, K+, and other electrolytes.

  • PO43– should not be infused with Ca2+, as this will cause Ca2+ to precipitate.

For key points on the management of hypophosphataemia, see Box 9.18.

Addisonian crisis: assessment

Adrenocortical insufficiency may be subclinical for days or months in otherwise well individuals. Stress, such as infection, trauma, or surgery, may precipitate an Addisonian crisis, with cardiovascular collapse and death if the condition is not suspected (see Boxes 9.19 and 9.20). Crises may also occur in patients with known Addison’s disease on replacement hydrocortisone if they fail to increase their steroid dose with infections. For causes of adrenal failure, see Box 9.19.

Presentation

  • Hypotension and cardiovascular collapse (shock).

  • Faintness, particularly on standing (postural hypotension).

  • Anorexia, weight loss, nausea, vomiting, and abdominal pain.

  • Hyponatraemia and hyperkalaemia.

  • Dehydration (thirst may not be apparent because of low Na+).

  • Salt cravings.

  • Diarrhoea in 20% of cases.

  • Symptoms of precipitant: fever, night sweats (infection), flank pain (haemorrhagic adrenal infarction), etc. Note signs/symptoms of other endocrinopathies.

  • Non-specific: weight loss, fatigue, weakness, myalgia, low-grade fever, headache, cramps, joint pain.

  • Hyperpigmentation suggests chronic hypoadrenalism.

  • Loss of axillary or pubic hair in women.

  • Psychiatric features are common and include asthenia, depression, apathy, and confusion (treatment with glucocorticoids reverses most psychiatric features).

Autoimmune adrenalitis

Accounts for 70–90% of cases in developed countries. Look for clinical evidence of other autoimmune disorders.

TB adrenalitis

Worldwide this is the most common cause of adrenal insufficiency.

Adrenal infiltration

Malignant secondaries may be present in the adrenals of a high percentage of patients with lung cancer, breast tumours, and malignant melanomas. Adrenal failure will only occur when over 90% of the gland is replaced by metastases.

The adrenals may alternatively be infiltrated in primary adrenal lymphoma, sarcoidosis, amyloidosis, and haemochromatosis.

Adrenal haemorrhage

This may complicate sepsis (meningococcal septicaemia, Waterhouse–Friderichsen syndrome), traumatic shock, coagulopathies, and ischaemic disorders.

  • Severe stress substantially increases the arterial blood supply to the adrenals. However, the adrenal gland has only one or two veins, making it vulnerable to venous thrombosis.

  • Blood tests: a precipitous drop in Hb, hyponatraemia, hyperkalaemia, acidosis, uraemia, and neutrophilia.

  • Waterhouse–Friderichsen syndrome is the association of bilateral adrenal haemorrhage with fulminant meningococcaemia. Adrenal haemorrhage can also be seen with other Gram –ve endotoxaemias such as Diplococcus pneumoniae, Haemophilus influenzae B, and DF-2 bacillus infections.

Hypopituitarism

As there is no mineralocorticoid deficiency (the release of which is renin, not ACTH-dependent), salt and water loss and shock are less profound than in primary Addison’s disease.

Drugs

Rifampicin, phenytoin, and phenobarbital accelerate the metabolism of cortisol and may precipitate an Addisonian crisis in partially compromised individuals or in those on a fixed replacement dose. Most adrenal crises precipitated by rifampicin occur within 2 weeks of initiating therapy.

Addisonian crisis: management

Investigations

  • U&Es

Hyponatraemia and hyperkalaemia (rarely >6.0mmol/L). High urea:creatinine ratio, indicative of hypovolaemia.

  • FBC

Anaemia [normal mean corpuscular volume (MCV)], moderate neutropenia with relative eosinophilia/leucocytosis.

  • Glucose

Hypoglycaemia (rarely).

  • Ca2+

May be high.

  • Cortisol

Baseline <400nmol/L. In sick patients, an expected cortisol level is in the range of 1000nmol/L (NB may be difficult to interpret in a patient on oestrogen therapy due to Diabetes and endocrine emergencies binding proteins).

  • ABG

Mild metabolic acidosis, respiratory failure.

  • Urine

MC&S for infection; urinary Na+ may be high despite hyponatraemia/hypovolaemia.

  • CXR

Previous TB, bronchial carcinoma.

  • AXR

Adrenal calcification.

Management

(See Box 9.21.)

  • Treatment may be required before the diagnosis is confirmed.

  • General measures include O2, continuous ECG monitoring, CVP monitoring, urinary catheter (for fluid balance), and broad-spectrum antibiotics for underlying infection.

  • Treat shock (Diabetes and endocrine emergencies Shock: management, pp. [link][link]): give IV normal saline for hypotension—1L stat, then depending on response and clinical signs. Inotropic support may be necessary.

  • Give IV glucose if hypoglycaemic.

  • If an adrenal crisis is suspected, the patient needs glucocorticoids urgently. Take blood for cortisol and ACTH measurement, and then administer glucocorticoid. Use of dexamethasone is now generally discouraged. Hydrocortisone should be administered IV (100mg qds initially). Commencing hydrocortisone can do little harm and may be lifesaving. The dose can later be reduced to an oral maintenance regime once the patient has stabilized, which may be up to 72h.

  • Short Synacthen® test (omit if the patient is known to have Addison’s disease): take baseline blood sample (serum) and administer tetracosactide (Synacthen®) 250 micrograms IM or IV. Take further samples at 30 and 60min for cortisol assay.

  • Fludrocortisone (50–100 micrograms daily PO) in patients with adrenal insufficiency when stabilized on oral replacement doses of hydrocortisone. Mineralocorticoid replacement is not initially required, as large doses of glucocorticoids confer some mineralocorticoid activity.

Prevention

  • Patients on long-term steroid therapy and/or known adrenocortical failure should be instructed to increase steroid intake for predictable stresses (e.g. elective surgery, acute illnesses with fever >38°C) or planned excessive exertion.

  • For mild illnesses, if not vomiting, double the oral dose. Vomiting requires IV/IM therapy (hydrocortisone 50–100mg qds).

  • For minor operations or procedures (e.g. cystoscopy), give hydrocortisone 100mg IV/IM as a single dose before the procedure, then give double the patient’s usual oral dose for the next 24h.

  • More serious illnesses require hydrocortisone 100mg qds IV/IM until recovered or for at least 72h, at which point the patient should then take double their normal oral dose for at least 48h when doses can be tailed back down to normal.

  • Double replacement doses when stabilized if on enzyme-inducing drugs.

See Table 9.3 for equivalent doses of glucocorticoids.

Table 9.3 Equivalent doses of glucocorticoids1

Drug

Equivalent dose (mg)

Dexamethasone

0.75

Methylprednisolone

4

Triamcinolone

4

Prednisolone

5

Hydrocortisone

20

Cortisone acetate

25

References

1. British National Formulary (1995). Section 6.3.2. Pharmaceutical Press, London; p. 615.Find this resource:

Further reading

National Institute for Health and Care Excellence (2016). Addison’s disease: management. Diabetes and endocrine emergencies https://cks.nice.org.uk/addisons-disease

Society for Endocrinology (2015). Adrenal insufficiency. Patient booklet. Diabetes and endocrine emergencies https://www.endocrinology.org/media/1767/16-04_adrenal-insufficiency.pdf

Myxoedema coma

A common precipitant of coma is the use of sedatives, and subsequent hypothermia, in elderly ♀ patients with undiagnosed hypothyroidism.

Myxoedema coma has a high mortality (30–50%) if inadequately treated.

Presentation

  • Altered mental status: disorientation, lethargy, frank psychosis.

  • Coma (symmetrical, slow-relaxing reflexes; ~25% have seizures).

  • Hypothermia.

  • Bradycardia, hypotension (rare).

  • Hypoventilation.

  • Hypoglycaemia.

Investigations

  • U&Es

Hyponatraemia is common (50%).

  • Glucose

Hypoglycaemia may occur.

  • FBC

Normocytic or macrocytic anaemia (there may be coexisting pernicious anaemia).

  • CK

Often elevated due to myositis.

  • TFT

T4 and TSH.

  • Cortisol

There may be coexisting adrenal insufficiency.

  • ABG

Hypoventilation causing respiratory acidosis.

  • Septic screen

Blood and urine cultures—full examination essential, especially in the elderly.

  • CXR

Pericardial effusion may occur, also as part of septic screen.

  • ECG

Small complexes (pericardial effusion), prolonged QT interval. MI can precipitate myxoedema coma in pre-existing disease.

Poor prognostic indicators

  • Hypotension: patients with hypothyroidism are usually hypertensive due to high compensatory endogenous catecholamines. Reduced BP indicates possible adrenal failure or cardiac disease. Response to inotropes is poor, as patients are usually maximally vasoconstricted.

  • Bradycardia.

  • Hypothermia unresponsive to treatment.

  • Sepsis.

  • Reduced GCS scores and use of sedative medications.

  • Hypoventilation and need for mechanical ventilation: is the most common cause of death in patients with myxoedema coma. The hypoxia responds poorly to O2 therapy which tends to exacerbate hypercapnia.

Management

(See Box 9.22.)

  • Transfer the patient to ICU and monitor closely.

  • Mechanical ventilation should be instituted for respiratory failure.

  • CVP line: patients may be hypertensive and hypovolaemic, as chronic myxoedema is compensated for by rising catecholamines.

  • Hydrocortisone (100mg IV 6- to 8-hourly) until adrenal insufficiency is excluded.

  • Institute thyroid hormone replacement therapy before confirming the diagnosis. No consensus has been reached about optimal thyroid hormone replacement. An accepted regimen includes administration of a loading dose of IV thyroxine (T4) 300–500 micrograms (depending on the patient’s age, weight, and risk of IHD), followed by daily IV doses of 50–100 micrograms until the patient can take oral T4. If there is no improvement within 24–48h, IV tri-iodothyronine (T3) (10 micrograms 8-hourly) is added and continued until there is clinical improvement and the patient is stable.

  • Broad-spectrum antibiotics should be given, since bacterial infection is a common precipitant of myxoedema coma.

  • Correct hypoglycaemia.

  • Hypothermia should be corrected gently. A space blanket is usually sufficient. Rapid external warming can cause inappropriate vasodilatation and cardiovascular collapse.

Precipitants of myxoedema coma

  • Drugs, including sedatives and tranquillizers.

  • Infection.

  • Stroke and MI.

  • Trauma.

Thyrotoxic crisis: assessment

The term thyrotoxic crisis refers to a constellation of symptoms and signs which together imply a poor prognosis. TFTs provide no discrimination between simple thyrotoxicosis and a thyrotoxic crisis (see Table 9.4). If the diagnosis has not been made, look for clues such as a goitre or exophthalmic Graves’ disease. The presentation may be confused with sepsis or malignant hyperthermia. A thyrotoxic crisis carries a mortality rate of 30–50%.

Table 9.4 Assessment of severity of a thyrotoxic crisis

Temperature (°C) Score

Pulse (bpm)

Cardiac failure

CNS effects

GI symptoms

Apyrexial

<99

Absent

Normal

Normal

0

>37.2

>99

Ankle oedema

5

>37.8

>110

Basal crepitations

Agitation

Diarrhoea, vomiting

10

>38.3

>120

Pulmonary oedema

15

>38.9

>130

Delirium

Unexplained jaundice

20

>39.4

>140

25

>40

Coma, seizure

30

Add the scores for each column.

Add an extra 10 points if AF is present.

Add 10 points if there is a definable precipitant.

A total score of over 45 indicates a thyroid crisis; a score of 25–44 indicates an impending crisis.

Presentation

Cardiovascular symptoms

  • Palpitations.

  • Tachycardia/tachyarrhythmias.

  • Cardiac failure/oedema.

  • Hypotension.

  • Arrhythmia.

  • Cardiovascular collapse.

GI symptoms

  • Diarrhoea.

  • Vomiting.

  • Jaundice.

  • Abdominal pain.

CNS symptoms

  • Anxiety/agitation.

  • Violent outbursts.

  • Psychosis/delirium.

  • Fitting/coma.

General symptoms

  • Fever.

  • Hyperventilation.

  • Sweating.

  • Polyuria.

Rarely, patients may present with an apathetic thyroid storm and lapse into a coma, with few other signs of thyrotoxicosis.

Precipitants of thyrotoxic crisis

  • Thyroid surgery/general surgery.

  • Withdrawal of antithyroid drug therapy/radioiodine therapy.

  • Thyroid palpation.

  • Iodinated contrast dyes.

  • Infection.

  • CVA/PE/MI.

  • Parturition.

  • DKA.

  • Trauma or emotional stress.

  • Burns.

Investigations

  • TFTs (most labs can perform an urgent TSH/free T4 if needed).

  • U&Es (? dehydration).

  • Ca2+ (may be elevated).

  • Glucose (may be low).

  • FBC (may see raised WBC).

  • LFTs (? jaundice, raised ALP).

  • Blood and urine cultures.

  • CXR (? pulmonary oedema or evidence of infection).

  • ECG (rate ? AF).

Thyrotoxic crisis: management

Patients with a thyrotoxic crisis or impending crisis

(See Box 9.23.)

  • Admit the patient to ICU.

  • Fluid balance: CVP monitoring is essential to avoid precipitating or worsening cardiac failure. In patients with arrhythmias, the CVP will not accurately reflect left-sided pressures and PA pressure monitoring should be considered. GI and insensible (pyrexia and excessive sweating) fluid losses may exceed 5L/day and must be replaced.

  • Fever should be treated with paracetamol and aggressive peripheral cooling techniques. Dantrolene has been occasionally used to control hyperthermia in a thyrotoxic crisis. Do not use salicylates which will displace T4 from thyroxine-binding globulin (TBG) and can hence worsen the storm.

  • β‎-block the patient with propranolol 60–80mg q4h PO or 1mg IV (repeated every 10min as necessary), with cardiac monitoring. Propranolol also inhibits peripheral T4 to T3 conversion. Fever, tachycardia, and tremor should respond immediately. An alternative is esmolol (15–30mg as a bolus, followed by 3–6mg/min infusion).

  • If β‎-blockade is contraindicated (e.g. asthma), consider a calcium channel blocker such as diltiazem.

  • Treat precipitating factors such as infection (e.g. cefuroxime 750mg IV tds).

  • High-dose antithyroid drugs: propylthiouracil (PTU) (600mg loading dose, then 200–300mg q4h PO/NG) is more effective than carbimazole (20mg 4-hourly), as it inhibits peripheral T4 to T3 conversion.

  • Consider bile acid sequestrants, e.g. colestyramine 2g qds, which can increase faecal excretion of T4.

  • Hydrocortisone: 100mg 6-hourly. This also inhibits conversion of T4 to T3.

  • Enoxaparin 20mg/day SC should be given to very sick patients at risk of thromboembolism.

  • Once organification of iodine has been blocked by antithyroid drugs, iodine can be used to inhibit T4 release from the thyroid gland (Wolff–Chaikoff effect). Lugol’s iodine contains 5% iodine and 10% potassium iodide in water. Give 1mL PO every 6h. Do not give Lugol’s iodine until at least 1h after the antithyroid drugs have been given. Any iodine given prior to antithyroid medication may increase thyroid hormone stores. Continue iodine-containing preparations for a maximum of 2 weeks (lithium 300mg 8-hourly is an alternative to iodine in allergic patients).

  • Monitor glucose levels 4-hourly and administer glucose 5–10% as required. Hepatic glycogen stores are readily depleted during a thyroid storm.

  • Consider plasmapheresis if refractory to treatment.

Continuing treatment

  • Response to treatment is gauged clinically and by serum T3 levels.

  • Stop iodine/potassium iodide/lithium and β‎-blockers when controlled.

  • Consider definitive treatment (e.g. surgery or radioactive iodine).

  • Treat AF in the usual way (Diabetes and endocrine emergencies Atrial fibrillation: assessment, pp. [link][link]). Higher doses of digoxin may be required, as its metabolism is Diabetes and endocrine emergencies. Amiodarone inhibits peripheral T4 to T3 conversion.

Further reading

American Thyroid Association. Hyperthyroidism (overactive). Diabetes and endocrine emergencies https://www.thyroid.org/hyperthyroidism

Carroll R, Matfin G. Endocrine and metabolic emergencies: thyroid storm. Ther Adv Endocrinol Metab 2010;1:139–45.Find this resource:

Pituitary apoplexy

Presentation

Pituitary infarction may be silent (‘subclinical pituitary apoplexy’). Apoplexy implies the presence of symptoms. The clinical manifestations may be due to leakage of blood/necrotic tissue into the subarachnoid space or rapid expansion of a suprasellar mass and pressure on local structures. This may be the presenting symptom of the pituitary tumour (see Box 9.24).

  • Headache occurs in 95% of cases (sudden onset; variable intensity).

  • Visual disturbance occurs in 70%, (usually bitemporal hemianopia).

  • Diabetes and endocrine emergencies level of consciousness.

  • Ocular palsy (up to 70%) causing diplopia, unilateral or bilateral.

  • Nausea/vomiting.

  • Meningism (common).

  • Hemiparesis or rarely seizures.

  • Fever, anosmia, CSF rhinorrhoea, and hypothalamic dysfunction (disturbed sympathetic autoregulation with abnormal BP control, respiration, and cardiac rhythm) are all described but are rare.

  • Altered mental state, lethargy, delirium, or coma.

  • Symptoms of a preceding pituitary tumour.

  • Acute hypopituitarism.

Clinically, pituitary apoplexy may be very difficult to distinguish from an SAH, bacterial meningitis, midbrain infarction (basilar artery occlusion), or cavernous sinus thrombosis. Transient neurological symptoms are common in the preceding few days.

The clinical course is variable. Headache and mild visual disturbance may develop slowly and persist for several weeks. In its most fulminant form, apoplexy may cause blindness, haemodynamic instability, coma, and death. Residual endocrine disturbance (panhypopituitarism) invariably occurs.

Investigations

  • U&Es: hyper- or hyponatraemia may occur.

  • Renal function, LFTs, clotting, and FBC.

  • Endocrine function tests (save clotted blood): cortisol, TFTs, prolactin, growth hormone (GH), IGF-1, luteinizing hormone (LH), follicle-stimulating hormone (FSH). The short Synacthen® test is unreliable in the first 2–3 weeks.

  • CT head: pituitary cuts with IV contrast will reveal a tumour mass or haemorrhage 24–48h after onset; however, CT is diagnostic in only ~30% of patients.

  • MRI (gadolinium-enhanced with pituitary views): is the investigation of choice, and urgent MRI is warranted. May be more informative in the subacute setting.

  • Formal visual field assessment: preferably in the first 24h if the patient is stable.

Management

(See Box 9.25.)

  • Stabilize the patient (airway, breathing, circulation).

  • Hydrocortisone 100mg IV should be given if the diagnosis is suspected, after the blood samples above have been collected, and is particularly important in patients with haemodynamic instability. Acute secondary adrenal insufficiency is a major cause of mortality.

  • Monitor U&Es and urine output for evidence of DI.

  • Patients with macroprolactinomas may respond to dopamine agonists.

  • Neurosurgical decompression may be indicated (seek neurosurgical review). Obtundation and visual deterioration are absolute indications for neurosurgery. Ideally patients will be nursed on a neurosurgical HDU. Patients without confusion or visual disturbance generally do well without surgery.

  • Assess pituitary function once the acute illness has resolved, and treat as necessary. A TSH level in the normal range may be inappropriate if T4 level is low in pituitary disease, but this may occur in the sick euthyroid state, characteristic of many seriously ill patients.

A scoring system has been suggested by the Society for Endocrinology for the assessment of severity of apoplexy, which could serve as a tool for monitoring of conservatively managed patients (see Table 9.5). This system could also be used as an aid to auditing outcomes in surgically and conservatively managed patients.

Table 9.5 Proposed pituitary apoplexy score**

Variable

Points

Level of consciousness

GCS score 15

0

GCS score <8–14

2

GCS score <8

4

Visual acuity

Normal* 6/6

0

Reduced—unilateral

1

Bilateral

2

Visual field defects

Normal

0

Unilateral

1

Bilateral

2

Ocular paresis

Absent

0

Present—unilateral

1

Bilateral

2

* No change from premorbid visual acuity.

** Reproduced from Rajasekaran S, et al. ‘UK guidelines for the management of pituitary apoplexy’. Clinical Endocrinology, 2011; 74(1): 920, with permission from John Wiley and Sons.

Further reading

Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf) 2011;74:9–20.Find this resource:

Hypopituitary coma

Hypopituitarism does not become evident until 75% of the adenohypophysis is destroyed, and at least 90% destruction is required for total loss of pituitary secretion. Complete loss of hormone secretion can rapidly become life-threatening and requires immediate therapy. In a mild or incomplete form, hypopituitarism can remain unsuspected for years.

Presentation

In the absence of stress, patients with severe hypopituitarism may have few symptoms or signs.

The development of pituitary hormone deficiency tends to follow a characteristic pattern, with GH and gonadotrophins lost early, followed by ACTH and TSH at a later stage. Symptoms of prolactin deficiency are rarely seen, except in the failure of lactation in Sheehan’s syndrome.

A general anaesthetic or infection may precipitate hypoglycaemia and coma, due to the combination of a lack of GH, cortisol, and T4, all of which have a counter-regulatory effect on insulin. See Box 9.26 for causes of panhypopituitarism.

Clues from the history include:

  • Known pituitary adenoma.

  • Recent difficult delivery: pituitary infarction following postpartum haemorrhage and vascular collapse is a recognized cause of hypopituitarism. Features include failure of lactation (deficiency of prolactin and oxytocin), failure of menstruation (lack of gonadotrophins), non-specific features, e.g. tiredness, weakness, loss of body hair, and loss of libido (due to ACTH deficiency, hypothyroidism, and gonadotrophin deficiency).

  • Men may give a history of impotence, lethargy, and loss of body hair.

  • Women report loss of menstruation.

Examination

  • Examination of the comatose patient is discussed under Diabetes and endocrine emergencies Coma: assessment, pp. [link][link].

  • Examine specifically for secondary sexual characteristics and physical signs of myxoedema.

  • Consider other causes for coma (Diabetes and endocrine emergencies Coma: assessment, pp. [link][link]).

Investigations

  • General investigations for patients in coma are discussed under Diabetes and endocrine emergencies Coma: assessment, pp. [link][link].

  • Take blood for baseline cortisol (9 a.m.), ACTH, TFTs, LH, FSH, prolactin, and GH.

  • Short Synacthen® test can be performed to test for adrenocortical reserve (Diabetes and endocrine emergencies Addisonian crisis: management, pp. [link][link]); however, a test of ACTH reserve, such as the insulin tolerance test or glucagon stress test, may be performed at a later date when the patient has stabilized.

  • Luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) tests may be performed at the same time as the short Synacthen® test but are rarely necessary.

  • Defer formal pituitary function testing until the patient is stable.

  • CT scan of the pituitary (tumour or empty sella).

  • MRI scan may give additional information.

Management

  • General measures are as for any patient in coma (Diabetes and endocrine emergencies Coma: assessment, pp. [link][link]).

  • Give IV normal saline to restore BP if the patient is in shock.

  • Give glucose if the patient is hypoglycaemic.

  • Hydrocortisone 100mg IV should be administered if the diagnosis is suspected and continued (100mg IV tds–qds).

  • Start liothyronine (10 micrograms bd) after hydrocortisone is started.

  • Investigate and treat any precipitating intercurrent infection.

  • If the patient fails to improve, consider other causes for coma (Diabetes and endocrine emergencies Coma: assessment, pp. [link][link]).

  • Long term, the patient will require replacement with hydrocortisone, thyroxine, testosterone or oestrogen/progesterone, and GH.

Phaeochromocytomas: assessment

  • Phaeochromocytomas are catecholamine-producing tumours usually involving one or both adrenal glands. Bilateral tumours are more likely to represent part of a familial syndrome, and tumour location, as well as risk of malignancy, varies depending on the genetic defect. Therefore, the previously described ‘rule of 10’ for phaeochromocytoma is no longer applicable. Phaeochromocytomas usually secrete adrenaline (AD) or noradrenaline (NA). A small proportion secrete dopamine (DA), when hypotension may occur.

  • Most are diagnosed during routine screening of hypertensive patients (they are found in only 0.1% of hypertensives). Pure AD-producing tumours may mimic septic shock due to AD-induced peripheral vasodilatation (β‎2-receptors).

Presentation

  • Classically a triad of episodic headaches, sweating, and tachycardia.

  • Hypertension (mild to severe sustained or uncontrolled paroxysmal hypertensive episodes) and orthostatic hypotension (low plasma volume); 50% have sustained elevated BP and 50% have paroxysmal elevations.

  • Anxiety attacks, tremor, palpitations, cold extremities, and pallor.

  • Cardiac dysrhythmias (including AF and VF) and dilated cardiomyopathy.

  • Hypertensive crises may be precipitated by β‎-blockers, tricyclic antidepressants, metoclopramide, and naloxone.

  • Unexplained lactic acidosis.

  • Triggers for hypertensive crises include surgery (particularly manipulation of the tumour itself), opiates, and contrast media.

See Box 9.27 for other causes of sympathetic overactivity.

Investigations

(See Box 9.28.)

  • Two to three 24h urine collections for measurement of metanephrines. These are more sensitive and specific than catecholamines, and false-negative results are rare. Measurements of 24h urine catecholamines remain useful and should be collected if metanephrine measurement is unavailable.

  • Urine should be collected in acid-containing bottles and kept refrigerated, as catecholamines are more stable at low pH and low temperature. Urine for metanephrines is collected in the same way.

  • Urinary creatinine and volume should be measured to verify an adequate (i.e. 24h) collection.

  • In patients who are at high risk for phaeochromocytoma (i.e. familial syndromes or previously surgically cured phaeochromocytoma or paraganglioma), both urine and plasma free metanephrine and normetanephrine should be measured if available (higher sensitivity—~99%).

  • Certain drugs (e.g. tricyclic antidepressants, levodopa, prochlorperazine, and calcium channel blockers) should be tapered and discontinued at least 2 weeks before any biochemical tests.

  • Catecholamine secretion may be appropriately Diabetes and endocrine emergencies in stress or illness [e.g. stroke, MI, CCF, obstructive sleep apnoea (OSA), and head injury].

  • FBC, U&Es, and glucose.

  • ECG (may see arrhythmias).

  • CXR: roughly 10% of phaeochromocytomas are malignant/metastatic.

  • Echocardiogram to assess LV function: this may very rarely identify a mediastinal paraganglioma as the source of catecholamines.

  • If the biochemical results are abnormal, imaging with CT or MRI of the abdomen/pelvis is required to locate the tumour. Caution: radiocontrast can cause catecholamine release.

  • 123-I-meta-iodobenzylguanidine (MIBG) is taken up by adrenergic tissue. An MIBG scan can detect metastases, multiple lesions, or tumours not detected by CT or MRI.

  • Plasma metanephrines: are highly sensitive and specific. They should be taken from a patient after at least 15min in a recumbent position. If plasma metanephrines are unavailable, plasma catecholamines should be collected from an indwelling cannula placed over 30min previously in a supine patient. Samples need to be taken directly to the lab (on ice) for centrifugation.

  • Selective venous sampling may be used to localize extra-adrenal tumours.

Phaeochromocytomas: management

Patients are usually volume-depleted at presentation and should be rehydrated prior to initiation of β‎-blockade; otherwise severe hypotension may occur. β‎-blockade alone may precipitate a hypertensive crisis and must never be given prior to adequate α‎-blockade. Labetalol is predominantly a β‎-blocker and should not be used alone. Long-acting α‎-blockers prevent escape episodes.

  • Adequate fluid replacement with CVP monitoring.

  • Acute hypertensive crises should be controlled with phentolamine (0.5–1mg IV bolus, repeated as necessary every 15–30min). Alternatively, start an infusion of nitroprusside (0.5–1.5 micrograms/kg/min; typical dose 100 micrograms/min).

  • Preparation for surgery:

    • Initiate oral α‎-blockade: phenoxybenzamine 10mg bd, increasing gradually to 20–30mg bd. Higher doses may be required. Monitor BP closely. Tumour β‎-stimulation may produce excessive vasodilatation and hypotension, requiring inotropic support. Recent studies have shown that prazosin or doxazosin are equally effective and are being used increasingly. α‎-blockade is necessary for several weeks prior to surgery to allow for adequate circulating volume expansion.

    • When the BP is controlled with phenoxybenzamine, add propranolol 10–20mg tds.

    • Invasive monitoring [PA (Swan–Ganz) catheter and arterial line] is mandatory.

  • Hypotension commonly occurs intraoperatively when the tumour is removed, and this should be managed with blood, plasma expanders, and inotropes, as required. Inotropes should only be used when the patient is appropriately fluid-replete. Expansion of intravascular volume 12h before surgery significantly reduces the frequency and severity of post-operative hypotension. Angiotensin II should be available as an alternative inotrope for cases of resistant hypotension.

For key points on the management of phaeochromocytomas, see Box 9.29.

References

2. Society for Endocrinology (2010). Protocol using oral phenoxybenzamine to prepare patients with catecholamine-secreting phaeochromocytoma and paraganglioma for surgery. Diabetes and endocrine emergencies https://www.endocrinology.org/media/1780/10-10_protocol_using_oral_phenoxybenzamine.pdf

Further reading

Endobible. Phaeochromocytoma. Diabetes and endocrine emergencies http://www.endobible.com/condition/phaeochromocytoma/

Polyuria

Definition: >3L of urine per day.

Presentation

  • Confusion (hyponatraemia or dehydration).

  • Coma.

  • Proteinuria on screening.

  • Depression or other psychiatric manifestations.

  • Renal stones.

Causes

  • Excessive fluid intake.

  • Endocrine dysfunction (DM, DI, hypercalcaemia, hyperthyroidism).

  • Hypokalaemia.

  • Intrinsic renal disease (polycystic kidneys, analgesic nephropathy, medullary cystic disease, amyloidosis) or renal recovery from ATN.

  • Post-obstructive uropathy, e.g. after catheterization of a patient in chronic retention.

  • Post-renal artery angioplasty.

  • Drugs (furosemide, alcohol, lithium, amphotericin B, vinblastine, demeclocycline, cisplatin).

History

  • Duration and severity (nocturia, frequency, water consumption at night).

  • Family history of DM, polycystic kidneys, and renal calculi.

  • Drug history (see Diabetes and endocrine emergencies Causes, p. [link]).

  • Renal calculi (hypercalcaemia).

  • Weakness (low K+), depression (hypercalcaemia).

  • Psychiatric history (psychogenic polydipsia; medications, i.e. lithium).

  • Endocrine history (menses, sexual function, lactation, pubic hair).

  • Other significant pathology (e.g. causes of amyloid).

Investigations

  • U&Es (renal disease, hypokalaemia).

  • TFTs.

  • Glucose (undiagnosed DM).

  • Ca2+, PO43–, and ALP.

  • Plasma and urine osmolality: a urine:plasma osmolality of <1.0 indicates DI, intrinsic renal disease (including low K+), or hysterical drinking.

  • AXR (nephrocalcinosis).

  • Lithium levels, if appropriate.

  • Dipstick protein and quantification, if indicated.

Management

  • Assess fluid status (JVP, BP, postural drop, weight charts, CVP).

  • Strict fluid balance and daily weights.

  • CVP line may be necessary.

  • Measure urinary Na+ and K+ (random spot samples will give an indication of the loss of Na+ or K+ initially, and if losses are great, accurate timed samples of <6h are possible).

  • Urine osmolality (if >750mOsm/kg, there is no abnormality in urine concentrating ability).

  • Replace fluid losses, as appropriate, to maintain normal homeostasis, using combinations of saline and glucose.

  • Monitor K+, Ca2+, PO43–, and Mg2+ daily or twice daily if necessary.

  • If lithium toxicity is present, see Diabetes and endocrine emergencies Lithium, pp. [link][link].

  • Avoid chasing fluids. At some point, a clinical judgement has to be made to stop replacing urinary losses with IV fluids, to allow the patient reach their ‘normal equilibrium’. Once the patient is optimally hydrated and is able to drink freely, then avoid replacing fluids IV to allow physiological homeostasis to occur.

  • If DI is suspected, arrange a water deprivation test (see Box 9.31). If anterior pituitary hormones are abnormal, do not perform a water deprivation test, as both cortisol and thyroid deficiency impair excretion of free water.

Malignant hyperthermia

Malignant hyperthermia is a drug- or stress-induced catabolic syndrome characterized by excessive muscular contractions, a sudden rise in body temperature, and cardiovascular collapse. It is often related to the use of anaesthetic agents. The incidence is 1:15 000, with a mortality which has significantly reduced from 80% down to <10% due to better treatment and Diabetes and endocrine emergencies awareness of the condition. The cause is unknown but may involve abnormal Ca2+ homeostasis in skeletal muscle cells. The condition seems to be inherited in an autosomal dominant manner, with variable penetrance. Early recognition of the condition is essential for treatment and survival.

See Box 9.32 for drugs precipitating malignant hyperthermia. See Box 9.33 for drugs considered safe in malignant hyperthermia.

Diagnosis

  • Malignant hyperthermia most commonly presents in patients in their early 20s. Early signs are muscular rigidity, sinus tachycardia and SVTs, Diabetes and endocrine emergencies carbon dioxide production with tachypnoea, and hypertension. Patients may sweat profusely and exhibit skin mottling.

  • Hyperthermia occurs late and may be rapidly followed by hypotension, mixed respiratory and metabolic acidosis, and hyperkalaemia, which gives rise to VT and cardiac arrest.

  • The condition almost always occurs perioperatively.

  • The differential diagnosis includes phaeochromocytoma, thyrotoxic crisis, narcotic-induced hyperthermia in patients taking MAOIs, and drug-induced hyperthermia [caused by cocaine, phencyclidine, amphetamine, lysergic acid diethylamide (LSD), tricyclics, and aspirin], and certain infections such as malaria.

  • Plasma CPK is high, as is myoglobin. Urine may therefore appear dark.

  • DIC is a further late manifestation.

Treatment

The aim of therapy is to decrease thermogenesis and promote heat loss.

  • Dantrolene: 1–2mg/kg IV every 5–10min to a maximum dose of 10mg/kg. Infusions should be repeated until cardiovascular and respiratory symptoms stabilize.

  • Stop any trigger/anaesthetic agent.

  • External surface cooling is helpful. All administered fluids should be chilled. Can stop once achieve a temperature <38.5°C.

  • Hyperventilate the patient with 100% O2 if under anaesthesia.

  • Patients should be managed on ITU with central venous access, an arterial line, and a urinary catheter.

  • Treat hyperkalaemia with insulin/glucose, calcium chloride, and dialysis, if necessary.

  • Consider bicarbonate for acidosis, under expert guidance.

  • Procainamide should be given to all patients to prevent ventricular dysrhythmias (increases uptake of Ca2+ and may reduce hyperthermia). Alternative treatment of arrhythmias includes amiodarone and β‎-blockers.

  • Hypotension should be treated with saline or colloids with isoprenaline. Dopaminergic and α‎-adrenergic agonists reduce heat dissipation and should be avoided.

  • Some authorities advocate prophylactic anticonvulsants, as seizures are common.

For management key points on malignant hyperthermia, see Box 9.34.

Further reading

Glahn KP, Ellis FR, Halsall PJ, et al. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group. Br J Anaesth 2010:105:417–20.Find this resource:

Neuroleptic malignant syndrome

The neuroleptic malignant syndrome results from an imbalance of dopaminergic neurotransmitters following neuroleptic drug use (see Box 9.35). The incidence is 0.5% in patients taking neuroleptic drugs. This syndrome is clinically distinct from malignant hyperthermia (Diabetes and endocrine emergencies Malignant hyperthermia, pp. [link][link]); it is not an allergic reaction. The mean age of onset is 40 years. Mortality is 10–20%.

Clinical features

  • Muscular rigidity, including dysphagia, dysarthria—early (96%).

  • Extrapyramidal signs (pseudo-parkinsonism), tremor (90%).

  • Oculogyric crisis.

  • Catatonia: muteness (95%).

  • Altered consciousness or coma.

  • Diabetes and endocrine emergencies serum CPK/AST (97%).

  • Pyrexia (rarely >40°C) follows onset of rigidity.

  • Autonomic instability, including tachyarrhythmias, labile BP, sweating, and tachypnoea.

The syndrome can occur within hours of initiating drug therapy but typically takes ~1 week. It can also occur following a dosage increase of a well-established drug.

Complications

  • Rhabdomyolysis (Diabetes and endocrine emergencies Rhabdomyolysis, pp. [link][link]), with raised CK.

  • Electrolyte disturbance, including hypocalcaemia, hypomagnesaemia, and hyperkalaemia.

  • Metabolic acidosis, often with raised lactate.

  • Renal (15%) and hepatic failure.

  • Fitting—rare.

  • Cardiovascular collapse.

  • DIC.

  • Respiratory failure.

Differential diagnosis

  • Malignant hyperthermia (Diabetes and endocrine emergencies Malignant hyperthermia, pp. [link][link]).

  • Serotonin syndrome.

  • Heat stroke.

  • CNS infections or vasculitides.

  • Other causes of catatonia.

  • Thyrotoxic crisis (Diabetes and endocrine emergencies Thyrotoxic crisis: assessment, p. [link]).

  • Phaeochromocytoma (Diabetes and endocrine emergencies Phaeochromocytomas: assessment, pp. [link][link]).

  • Drug-induced hyperthermia (caused by cocaine, LSD, phencyclidine, amphetamine, tricyclics, and aspirin).

Management

(See Box 9.36.)

  • Withdrawal of causative agent (unless the precipitant is withdrawal of the dopaminergic agent, in which case it should be reinstated).

  • Admission to ITU.

  • Dantrolene (1–2mg/kg every 6h, up to a maximum 300mg/day).

  • Paralysis and ventilation (curare, pancuronium).

  • Antiarrhythmics, as necessary.

  • Fluid resuscitation for raised CK or rhabdomyolysis.

  • Treat hyperthermia with cooling blankets. Consider paracetamol use.

  • Thromboprophylaxis.

  • Bromocriptine, amantadine, levodopa (increase dopaminergic tone and reduce rigidity, thermogenesis, and extrapyramidal symptoms). Most agents are used on the basis of experience or anecdotal evidence, with little supporting evidence. The condition carries high morbidity and mortality.

Notes:

* Plus K+ replacement; see Diabetes and endocrine emergencies Potassium replacement, p. [link]

* If repeated three times, consider IV 10% glucose at 100mL/h or 1mg glucagon IM (if no IV access and not given already). Once blood glucose >4mmol/L, give 20g of long-acting carbohydrate (two biscuits or a slice of bread) or the next meal if due. If IM glucagon given, give 40g of long-acting carbohydrate to replenish glycogen stores. If NBM, give 10% glucose infusion at 10mL/h and review glucose hourly.