210

REVIEW

Emergency management of diabetic ketoacidosis in

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adults
R D Hardern, N D Quinn
.............................................................................................................................

Emerg Med J 2003;20:210–213

The authors propose a regimen for managing diabetic cause serious diagnostic difficulty where the
ketoacidosis in adults based on available evidence and patient is unconscious or DKA is the first presen-
tation of diabetes (a past history of diabetes mel-
their experince in the emergency department. litus will be absent in 1 in 10 patients). The possi-
.......................................................................... bility of DKA (or other metabolic acidosis) should
be considered whenever assessing a patient who
presents with “hyperventilation”4 and it is always

D
iabetic ketoacidosis (DKA) is a potentially
essential to measure the blood glucose early in the
fatal metabolic disorder presenting most
resuscitation of any unconscious patient.
weeks in most accident and emergency
Polyuria, polydipsia, and weakness are usually
(A&E) departments.1 The disorder can have
present. Nausea, vomiting, or abdominal pain
significant mortality if misdiagnosed or mis-
may predominate. If the patient is already being
treated. Numerous management strategies have
treated with insulin, there may be a history of
been described. Our aim is to describe a regimen
reduced or omitted insulin. Chest pain may be
that is based, as far as possible, on available
described if DKA complicates acute myocardial
evidence but also on our experience in managing
infarction, although silent infarction may occur.
patients with DKA in the A&E department and
On examination the patient has an increased
on inpatient wards.
depth and rate of respiration. The mouth, tongue
A literature search was carried out on Medline
and lips are dry. The majority of doctors can smell
and the Cochrane Databases using “diabetic
ketones on the patient’s breath but this is an
ketoacidosis” as a MeSH heading and as text-
unreliable sign. There may be other signs of
word. High yield journals were hand searched.
volume depletion. Signs of infection (for example,
Papers identified were appraised in the ways
lobar pneumonia) should be sought; absence of
described in the Users’ guide series published in
fever does not exclude infection.
JAMA.
We will not be discussing the derangements in
intermediary metabolism involved, nor would we Bedside tests
suggest extrapolating the proposed regimen to A capillary glucose measurement should be made
children. Although some of the issues discussed (ensure there is no sugar on the skin where skin
may be considered by some to be outwith the prick is made).
remit of A&E medicine it would seem prudent to Defining DKA as serum glucose >250 mg/dl
ensure that A&E staff were aware of the probable (>14 mM), metabolic acidosis with corrected
management of such patients in the hours after pH<7.30 or serum bicarbonate <15 mM and
they leave the A&E department. ketonaemia, the sensitivity of urine ketone dip
test for ketonaemia in patients with DKA is 97%
AETIOLOGY AND DEFINITION (95% CI 92% to 99%).5 The absence of ketonuria
makes the diagnosis of DKA unlikely. It is possible
DKA may be the first presentation of diabetes.
that clinical staff in the study were using negative
Insulin error (with or without intercurrent
urine dip stick test to rule out DKA; the study
illness) is the most common precipitating factor,
would therefore overestimate its sensitivity. Few
accounting for nearly two thirds of cases (exclud-
laboratories offer an urgent ketone level; an esti-
ing those where DKA was the first presentation of
mate of the severity of ketonaemia can be made
diabetes mellitus).2
from the anion gap (available immediately on
The main features of DKA are hyperglycaemia,
some “blood gas analysers”); an anion gap >20
metabolic acidosis with a high anion gap and
See end of article for mM is abnormal.
heavy ketonuria (box 1). This contrasts with the
authors’ affiliations Acute myocardial infarction can precipitate
....................... other hyperglycaemic diabetic emergency of
DKA. A 12 lead ECG should be recorded.
hyperosmolar non-ketotic hyperglycaemia where
Correspondence to: there is no acidosis, absent or minimal ketonuria
Dr R D Hardern,
Department of Accident
but often very high glucose levels (>33 mM) and
and Emergency Medicine, very high serum sodium levels (>150 mM).3 Box 1 The usual features of diabetic
The General Infirmary, ketoacidosis
Great George Street, Leeds
LS1 3EX, UK; DIAGNOSIS
Clinical findings • Hyperglycaemia (>14 mM).
richard.hardern@
leedsth.nhs.uk • Metabolic acidosis (pH<7.35 and bicarbo-
There are no specific clinical signs that confirm or
nate <15 mM).
Accepted for publication
refute the diagnosis of DKA. The diagnosis is • High anion gap.
12 December 2001 comparatively straight forward where there is a • Ketonaemia/heavy (3+) ketonuria.
....................... clear history that the patient has diabetes but can

www.emjonline.com
Diabetic ketoacidosis 211

Box 2 Key points in diagnosis of DKA Box 3 Key points in treatment

• There are no specific physical symptoms or signs • Get experienced help

Emerg Med J: first published as 10.1136/emj.20.3.210 on 1 May 2003. Downloaded from http://emj.bmj.com/ on 8 June 2018 by guest. Protected by copyright.
• Rule out DKA and other causes of metabolic acidosis before • Obtain good venous access and send off blood samples
making a diagnosis of hysterical hyperventilation • Consider nasogastric tube if patient not alert
• Check capillary blood glucose early but always follow this • Consider urinary catheter if haemodynamically unstable
with a formal venous blood glucose level • 0.9% saline 500 ml/h for four hours then 250 ml/h until
• Test urine for ketones euvolaemic is an effective fluid regime (unless the patient is
• Arterial blood is NOT needed as routine shocked at presentation)
• Blood potassium levels should be measured hourly (hyper- • Insulin, by continuous intravenous infusion at 0.1 unit/
kalaemic and hypokalaemic cardiac arrest are common kg/h. The fall in [glucose] should not exceed 5 mM/h.
causes of death in patients with DKA2) • Start potassium supplementation after insulin treatment once
• Venous blood glucose should be measured hourly during [K+] is below the upper limit of the reference range.
insulin infusion • The administration of bicarbonate does NOT increase bio-
• A chart should be started to continuously record vital signs, chemical or clinical recovery.
urine output, and the results of all tests.

saline is the fluid usually used in the initial management of

Special tests DKA though no formal comparisons with 0.45% saline or
It is not necessary to take arterial blood as a routine in Ringer’s solution have been reported. Volume status can be
suspected DKA; venous blood can be sampled in a pre- assessed on the basis of clinical assessment (such as heart rate
heparinised syringe and then analysed with a “blood gas ana- and BP), from urine output (a high urine output may indicate
lyser”. The mean difference between arterial and venous pH in only osmotic diuresis but a low urine output should trigger a
DKA is 0.03 (CI not given in text, but in only 1 case of 44 was thorough assessment of renal function and the state of hydra-
the difference greater than 0.1).6 Arterial sampling should be tion), from urea measurements, and (sometimes) from
reserved for cases when respiratory failure is suspected. invasive monitoring.
Despite a significant reduction in total body potassium, the In patients with significant comorbidity (especially cardiac
serum concentration is usually normal or high at presentation disease) invasive haemodynamic monitoring may help to
because of a shift into the extracellular compartment. The guide the rate of fluid replacement. This has not been
steepest decline of [potassium] occurs in the first few hours of subjected to prospective evaluation and the potential compli-
treatment; many recommend that values are checked at least cations of attempted central cannulation in volume depleted
hourly during this phase. patients should be borne in mind. This is not a group of
Venous glucose should be measured hourly. Management patients in which to “practise” central cannulation.
should be based on capillary glucose measurements only after Once [glucose] has fallen to around 14 mM (a value based
these have been found to agree with venous levels (at presen- on tradition more than anything else) 5% dextrose (with
tation the degree of hyperglycaemia may render the capillary appropriate potassium) is given rather than saline. Adminis-
measurement inaccurate). tering hypertonic dextrose (1 litre 10% dextrose + 40 units
Leucocytosis is usual and should not be interpreted as a sign insulin at 250 ml/h) rather than isotonic dextrose (1 litre 5%
of infection. Routine treatment with antibiotics is not dextrose + 10 units insulin at 250 ml/h) may accelerate the
indicated; blood and urine should be cultured. clearance of ketone bodies but also causes a rise in [glucose]
without an additional improvement in blood pH or
TREATMENT bicarbonate.8
DKA is a complex life threatening problem and the
management should not be left to inexperienced staff. There Insulin
should be early consultation between A&E staff and specialist Type of insulin
diabetes teams. Patients with DKA need four things; A soluble insulin is normally used with the aim of permitting
• Fluid more rapid titration of circulating insulin levels (though there
• Insulin are no trial data comparing soluble against other types of
insulin). If an intravenous bolus is followed by an intravenous
• Potassium infusion steady state insulin levels are reached very quickly.
• Education The half life of circulating insulin is five minutes; use of an
Early venous access is essential. In shocked patients large intravenous infusion has the advantage over intermittent
bore cannulas should be sited and standard measures boluses of permitting a more rapid reduction in insulin level.
instituted (oxygen, cardiac monitor, regular measurement of
pulse and blood pressure). Avoid central lines unless essential Dose of insulin
for monitoring in severely ill patients. Adjuncts to resuscita- We usually give a bolus of six units then an infusion of 6
tion should include a nasogastric tube in patients who are not units/h when starting treatment of an adult with DKA (0.1
alert (gastroparesis occurs and aspiration of gastric contents is units/kg for patients who weigh less than 60 kg). Higher doses
a complication of DKA). A urinary catheter is needed if are associated with an increased risk of hypoglycaemia. A tar-
patients are haemodynamically unstable and need accurate get reduction in [glucose] of 5 mM/h has been suggested
measurement of urine output. though this has not been subjected to evaluation.9 Rather than
using a “sliding scale”, we suggest that an infusion rate is
Hydration started and then reviewed by a doctor every one to two hours
A regimen suitable for patients who are not shocked or oligu- (they should be reviewing the patient at least this frequently
ric (<30 ml/h) is 500 ml/h of 0.9% saline for four hours anyway). This is analagous to reviewing hypotensive or
followed by 250 ml/h for the next four hours. This is associated shocked patients frequently rather than prewriting their fluids
with as rapid a correction of acidosis and hyperglycaemia as a for several hours.
regimen using twice these rates.7 Unnecessarily large volumes Failure to achieve a reduction with this regimen for insulin
of intravenous fluids should be avoided because of the high should prompt a check of intravenous access, all connections,
case fatality rate of cerebral oedema. Physiological (0.9%) and the infusion device. If no mechanical cause is found a

www.emjonline.com
212 Hardern, Quinn

failure to respond may represent untreated infection or inad- oxygenation and increasing lactate production. Bicarbonate
equate volume replacement. An additional bolus of insulin infusions can cause a rise in PaCO2; rapid diffusion across cell
(equivalent to the previous hourly rate) should be given and membranes can actually worsen intracellular acidosis, espe-

Emerg Med J: first published as 10.1136/emj.20.3.210 on 1 May 2003. Downloaded from http://emj.bmj.com/ on 8 June 2018 by guest. Protected by copyright.
the infusion rate doubled. cially in situations when the patient is unable to compensate
Conventional insulin infusion rates are often insufficient to by increasing carbon dioxide excretion. During the recovery
achieve normoglycaemia in patients on an adrenaline (epine- phase of DKA any lactate produced during tissue hypoxia is
phrine) infusion because of the antagonistic effects of metabolised to bicarbonate leading to rebound alkalosis.
adrenaline; the insulin infusion rate should be increased until
[glucose] falls at the desired rate. There is no unsafe upper Phosphate
limit provided frequent clinical and biochemical reassessment Phosphate levels are affected in DKA in much the same way as
is carried out. potassium (that is, extracellular shift but depleted total body
levels). A small study found that the addition of phosphate to
Duration of insulin infusion standard treatment did not reduce the time taken to reach
Ketone bodies are cleared more slowly than glucose. The insu- recovery indices of bicarbonate, pH, or glucose.16 Differences in
lin infusion should be continued until ketosis and acidosis magnesium and 2,3DPG levels and in P50 (the PaO2 at which
have cleared. Discontinuing insulin on the basis of (near) nor- haemoglobin is 50% saturated) were not statistically signifi-
mal glucose levels can result in recurrence of ketoacidosis. If, cant. In another study phosphate supplementation (15 or 45
however, the insulin infusion is continued after [glucose] nor- mmol) did not affect the rate of correction of [glucose],
malises there is a danger of hypoglycaemia unless hypertonic [bicarbonate] or pH.17
dextrose in infused. The first subcutaneous injection must be
given before the insulin infusion is stopped; otherwise insulin PROGNOSIS
levels may fall too low and ketoacidosis recur. In most hospi- An overall mortality rate of 3.9% was reported from Birming-
tals staffing is better in office hours than out of hours. It may ham (United Kingdom) for the period 1971 to 1991.2 Many of
therefore be preferable to change from intravenous to these deaths occurred in patients with significant comorbid-
subcutaneous insulin in the morning rather than in the ity; it may not be possible to reduce the mortality rate further.
evening. The mortality rate increases with age: 1.9% in those aged 12 to
69 and 19.6% in those aged 70 or more (95% CI for the differ-
Potassium
ence in mortality between the two age groups 9.9% to 25.4%).
Significant hypokalaemia is the most common life threatening
If cerebral oedema complicates DKA the mortality rate is
electrolyte derangement that occurs during the treatment of
over 90%. Although most cases occur in patients younger than
DKA. Intravenous potassium replacement will be required
20 years it can occur in older patients. Avoiding falls in osmo-
after insulin is given as potassium will move into cells. Potas-
lality greater than 5 mosm/h has been suggested as a way of
sium replacement should not be started before insulin
reducing the likelihood of developing cerebraloedema.9
treatment; extracellular levels may otherwise rise dangerously
high. Potassium replacement should be given as soon as insu-
lin and fluid are started and the [K] level is known to be below FUTURE DEVELOPMENTS
the upper limit of the reference range. Regimens for There are insulin analogues (Aspart and LisPro) that are
potassium supplementation have not been formally evaluated. ultra-fast acting insulins with shorter half lives than soluble
One suitable regimen for potassium replacement has been insulins currently in use. There is no evidence that the use of
proposed10: such insulins increases the risk of DKA and the management
of patients with diabetes treated with these agents is no
• Start KCl once [K] is normal or low.
different from that outlined above.
• 20 mmol/h is an average dose; adjust according to hourly Continuous subcutaneous insulin infusions are commonly
levels. used in continental Europe to treat type I diabetes mellitus
• If the initial level is high, start KCl as soon as level falls into and their use is increasing in the UK. They were initially asso-
normal range. ciated with an increased risk of DKA because of equipment
failure.18 19 As the technology has improved this risk has fallen.
Education Treatment of DKA in patients usually treated with continuous
Many cases of DKA occur after incorrect reduction or omission subcutaneous insulin infusions does not differ from the
of insulin treatment. It is vital that patients who develop DKA conventional approach.
receive, before discharge from hospital, education about how
to manage their insulin in the event of intercurrent illness. .....................
This information should have been provided previously to all Authors’ affiliations
patients treated with insulin. R D Hardern, Department of Accident and Emergency Medicine, The
General Infirmary, Leeds, UK
Bicarbonate N D Quinn, Diabetes Centre, The General Infirmary, Leeds
Severe acidosis has adverse effects on many organs, especially
the brain and the heart. It may, therefore, seem appealing to
give bicarbonate as treatment for the metabolic acidosis that REFERENCES
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RCTs) have failed to find evidence of faster biochemical recov- ketoacidosis: are clinical guidelines implemented effectively? Diabet Med
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mM sodium bicarbonate over one hour) delayed the fall in ketoacidosis. Diabet Med 1993;10:282–4.
4 Treasure RAR, Fowler PBS, Millington HT, et al. Misdiagnosis of
total ketone bodies and lactate levels.15 diabetic ketoacidosis as hyperventilation syndrome. BMJ 1987;294:630.
Sodium bicarbonate is both hypertonic and hyperosmolar. 5 Hendey GW, Schwab T, Soliz T. Urine ketone dip test as a screen for
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6 Brandenburg MA, Dire DJ. Comparison of arterial and venous blood
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Clinical Evidence—Call for contributors

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