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DOI: 10.1111/j.1464-5491.2011.03246.x
Abstract
The Joint British Diabetes Societies guidelines for the management of diabetic ketoacidosis (these do not cover Hyperosmolar
Hyperglycaemic Syndrome) are available in full at:
(i) http://www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/The-Management-of-Diabetic-Ketoacidosis-in-Adults;
(ii) http://www.diabetes.nhs.uk/publications_and_resources/reports_and_guidance;
(iii) http://www.diabetologists-abcd.org.uk/JBDS_DKA_Management.pdf.
This article summarizes the main changes from previous guidelines and discusses the rationale for the new recommendations.
The key points are:
Monitoring of the response to treatment
(i) The method of choice for monitoring the response to treatment is bedside measurement of capillary blood ketones using a
ketone meter.
(ii) If blood ketone measurement is not available, venous pH and bicarbonate should be used in conjunction with bedside blood
glucose monitoring to assess treatment response.
(iii) Venous blood should be used rather than arterial (unless respiratory problems dictate otherwise) in blood gas analysers.
(iv) Intermittent laboratory confirmation of pH, bicarbonate and electrolytes only.
Insulin administration
(i) Insulin should be infused intravenously at a weight-based fixed rate until the ketosis has resolved.
(ii) When the blood glucose falls below 14 mmol ⁄ l, 10% glucose should be added to allow the fixed-rate insulin to be continued.
(iii) If already taking, long-acting insulin analogues such as insulin glargine (Lantus, Sanofi Aventis, Guildford, Surry, UK) or
insulin detemir (Levemir, Novo Nordisk, Crawley, West Sussex, UK.) should be continued in usual doses.
Delivery of care
(i) The diabetes specialist team should be involved as soon as possible.
(ii) Patients should be nursed in areas where staff are experienced in the management of ketoacidosis.
Introduction
Correspondence to: Mark Savage, North Manchester General Diabetic ketoacidosis is defined by the biochemical triad of
Hospital—Diabetes Centre, Delauneys Road, Manchester M8 5RB, UK.
E-mail: mark.savage@pat.nhs.uk ketonaemia, hyperglycaemia and acidaemia. The incidence is
1
difficult to establish, ranging from 4.6 to 8 episodes per 1000
The Joint British Diabetes Societies consists of: the Association of British
Clinical Diabetologists; the British Society for Paediatric Endocrinology and patients with diabetes in population-based studies from the USA
Diabetes and the Association of Children’s Diabetes Clinicians; the Diabetes [1]. In England, more than 11% of people with Type 1 diabetes
Inpatient Specialist Nurse (DISN) Group; Diabetes UK; NHS Diabetes had an episode of diabetic ketoacidosis in the years between 2004
(England); the Northern Ireland Diabetologist’s Group; the Society of Acute
Medicine; the Scottish Diabetes Group; and the Welsh Endocrine and and 2009 [2]. It remains a life-threatening condition despite
Diabetes Society. improvements in diabetes care [3,4]. Mortality in the UK from
diabetic ketoacidosis is low at approximately 2% [5], but each (ii) blood glucose over 11 mmol ⁄ l or known diabetes
death is potentially avoidable. There is a need to improve mellitus;
patient education and attendance at clinics and to raise (iii) venous bicarbonate (HCO3)) below 15 mmol ⁄ l and ⁄ or
awareness of diabetic ketoacidosis and its management venous pH less than 7.3.
amongst healthcare professionals. The mortality rate remains
Note: this excludes Hyperosmolar Hyperglycaemic Syndrome
high in developing countries and among non-hospitalized
which occurs in Type 2 diabetes and is generally not associated
patients [6]. This illustrates the importance of early diagnosis
with acidosis caused by ketonaemia.
and implementation of effective prevention programmes.
Cerebral oedema remains the most common cause of
mortality, particularly in young children and adolescents. In Developments in management
the adult population, hypokalaemia, adult respiratory distress
Until recently, the management of diabetic ketoacidosis has
syndrome ⁄ acute lung injury and co-morbid states such as
focused on lowering the elevated blood glucose with fluids and
pneumonia, acute myocardial infarction and sepsis are all
insulin, on the assumption that this would suppress ketogenesis
associated with increased mortality [7].
and reverse the acidosis. Metabolic improvement was assessed
There are several existing national and international guidelines
using arterial pH and serum bicarbonate. The development of
for the management of diabetic ketoacidosis in both adults and
blood ketone meters allows us to focus on the underlying
children [8–12]. The Joint British Diabetes Societies guidelines
metabolic abnormality (ketonaemia). This simplifies treatment
take into account developments in technology and changes in the
of patients who present with only modest elevation of blood
presentation of diabetic ketoacidosis over the last few years. In
glucose, but with acidosis secondary to ketonaemia–
the last decade, the development of technology for near patient
‘euglycaemic diabetic ketoacidosis’ [1,13,14]. This clinical
testing of ketones has allowed monitoring of 3-beta-
presentation is encountered more frequently as improved
hydroxybutyrate at the bedside. As a result, the focus of
patient education with increased blood glucose and ketone
monitoring has shifted from the blood glucose to the blood
monitoring has led to partial treatment of diabetic ketoacidosis
ketone level, which is a more accurate marker of the resolution of
prior to admission and lower blood glucose levels at presentation.
the acidosis.
The facility to monitor blood ketones and blood glucose is an
These guidelines are evidence based wherever possible, but are
important advance in the management of diabetic ketoacidosis
also drawn from accumulated professional knowledge and
[15–21]. Portable blood ketone analysers that are compliant with
consensus agreement. They are intended for use by any
approved laboratory protocols are now available with in-built
healthcare professional managing diabetic ketoacidosis in
quality assessment and calibration; these also have computerized
adults. They are not meant to be the definitive guideline on the
links to the laboratory and bar code scanning of patients’
management of diabetic ketoacidosis. It is clear that there are
identification labels. Bedside monitoring has been shown to be
gaps in the published evidence and that these guidelines should be
helpful in the clinical situation of diabetic ketoacidosis (17].
audited and results of these audits and of research should lead to
Access to analysers for blood gas and electrolyte measurement is
revisions as necessary.
now therefore relatively easy and results are available within a
few minutes rather than hours. Therefore, glucose, ketones and
Pathophysiology electrolytes, including bicarbonate and venous pH, should be
assessed at or near the bedside. This recommendation raises
Diabetic ketoacidosis occurs as a consequence of absolute or
important issues:
relative insulin deficiency, usually accompanied by an increase in
(i) Staff must be trained in the use of blood glucose and
counter-regulatory hormones such as glucagon, cortisol and
blood ketone meters (note: those used in hospital units
epinephrine. This hormonal imbalance leads to hepatic
are not the same as used by patients).
gluconeogenesis and glycogenolysis, resulting in severe
(ii) Meters should be subject to rigorous quality assurance
hyperglycaemia. Enhanced lipolysis increases serum free fatty
and under the control of the Near Patient Testing
acids with production of large quantities of ketone bodies
Coordinator, or equivalent.
(acetone, acetoacetate and 3-beta-hydroxybutyrate) and
(iii) Laboratory measurement will be required in certain
consequent metabolic acidosis. The osmotic diuresis induced
circumstances, such as when blood glucose or ketone
by hyperglycaemia combined with ketone-induced nausea and
meters are ‘out of range’.
vomiting leads to severe fluid depletion and life-threatening
(iv) Blood gas analysers must be readily available to
electrolyte imbalance.
admitting teams.
It is recognized that not all units have access to ketone meters and
Diagnosis
that there is a lead-in time to getting the appropriate meters that
The diagnostic criteria for diabetic ketoacidosis are: are laboratory approved. Thus, management guidance is also
(i) ketonaemia 3 mmol ⁄ l and over or significant ketonuria given based on the rate of rise of bicarbonate and fall in blood
(more than 2 + on standard urine sticks); glucose.
and early warning symptoms. Failure to do so is a missed Solution of 0.9% sodium chloride vs. Hartmann’s solution for
educational opportunity. Things to consider include: fluid replacement?
(i) identification of precipitating factors such as infection or There has been much debate recently about the relative merits of
omission of insulin injections; these two solutions [31].
(ii) education to prevent recurrence; for example, provision Advantages of 0.9% sodium chloride: decades of clinical
of written sick day rules; experience; readily available in clinical areas; commercially
(iii) warning about potential insulin ineffectiveness; for available ready mixed with potassium at required
example, the patient’s insulin may be expired or concentrations; compliant with National Safety Patient Agency
denatured; advice regarding safe practice with injectable potassium [32].
(iv) provision of hand-held ketone meters with education on Disadvantages: use of large volumes can lead to
management of ketonaemia. hyperchloraemic metabolic acidosis, which may cause renal
arteriolar vasoconstriction, oliguria and delayed resolution of
acidosis.
Controversial areas Advantages of compound sodium (Hartmann’s): balanced
The clinical assessment and aims of treatment in the management crystalloid with minimal tendency to hyperchloraemic metabolic
of diabetic ketoacidosis are not controversial. However, there is acidosis.
disagreement about the optimum treatment regimen and, where Disadvantages: insufficient potassium if used alone; not
the evidence base is not strong; recommendations are based on commercially available with adequate premixed potassium and
consensus and experience. Some of the controversial points will not compliant with National Safety Patient Agency guidance for
be considered and good practice recommendations are made. safe use of potassium in general clinical areas [32]; unfamiliar and
not routinely kept on medical wards.
Therefore, 0.9% sodium chloride solution is recommended as
Arterial or venous pH and bicarbonate measurements? the fluid of choice for resuscitation in all clinical areas as it
Recent evidence shows that the difference between venous and supports safe practice and is available, ready to use, with
arterial pH is 0.02–0.15 pH units and the difference between adequate ready-mixed potassium.
arterial and venous bicarbonate is 1.88 mmol ⁄ l [27,28]. This
difference will not influence either diagnosis or management of Continuation of long-acting insulin analogues?
diabetic ketoacidosis and it is not necessary to use arterial blood
to measure acid base status [29]. Venous blood can be used in In the last few years, the use of long-acting basal insulin
portable and fixed blood gas analysers and therefore venous analogues (Levemir, Lantus) has become widespread and
measurements (bicarbonate, pH and potassium) are easily others may be launched on the market soon. Continuation of
obtained in most admitting units. Arterial line insertion should long-acting analogues during the initial management of
only be performed if frequent arterial oxygen level measurements diabetic ketoacidosis provides background insulin when the
or blood pressure monitoring is required in the critically unwell intravenous insulin is discontinued. Although there is no
patient. evidence on which to base recommendations about the
continuation of long-acting insulin analogues during the
acute episode, maintaining the normal daily dose of these
Colloid vs. crystalloid? insulins is unlikely to adversely affect the blood glucose
Many guidelines recommend initial fluid resuscitation with response to the intravenous infusion and should facilitate a
colloid in hypotensive patients. However, the hypotension results smoother transition from the intravenous insulin infusion to
from a loss of electrolyte solution and it is more physiological to subcutaneous insulin. This avoids rebound hyperglycaemia and
replace with crystalloid. A recent Cochrane review did not ketogenesis when intravenous insulin is stopped and may avoid
support the use of colloid in preference to crystalloid fluid [30]. excess length of stay. This advice only applies to long-acting
analogues and does not obviate the need to give short-acting
insulin before discontinuing the intravenous insulin infusion. If
Rate of fluid replacement? the patient is not taking a long-acting analogue, background
There is concern that rapid fluid replacement may lead to cerebral insulin (isophane) should be reintroduced before the
oedema in children and young adults. National and international intravenous infusion is discontinued.
paediatric guidelines recommend cautious fluid replacement over
48 h. Existing adult guidelines [9,10,12] all recommend rapid Use of a priming dose (bolus) of insulin?
initial fluid replacement in the first few hours. No randomized
controlled trials exist to guide decision making in this area. It has been demonstrated that a priming dose of insulin is not
Therefore, cautious fluid replacement is recommended in small necessary, provided that the insulin infusion is started promptly
young adults who are not shocked at presentation. at a dose of 0.14 unit kg)1 h)1 [33]. Although the insulin infusion
513
DIABETICMedicine
FIGURE 1 The management of diabetic ketoacidosis in adults. Summary of the guidelines. Reproduced from NHS Diabetes (2010), with permission of Joint British Diabetes Societies.
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