[PPT] - An Update in Diabetic Ketoacidosis (DKA) and Hyperglycemic PowerPoint Presentation

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An Update in Diabetic Ketoacidosis (DKA) and Hyperglycemic Hyperosmolar State (HHS)

Dr Ketan Dhatariya MBBS MSc MD MS FRCP

Consultant in Diabetes and Endocrinology Norfolk and Norwich University Hospitals

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Financial Disclosures

In the last 12 months I have attended advisory

board meetings for

– Eli Lilly – Sanofi Aventis – Roche Diagnostics

I have received travel grants from

– Genentech – Roche Diagnostics – Eli Lilly – Novo Nordisk

All of my conflicts of interest are available on

www.norfolkdiabetes.com

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Acknowledgements

Ian Nunney
Gillian Iceton
Kath Higgins
Mike Sampson
JBDS
ABCD
DISN UK
Diabetes UK

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Outline

A bit of history
Where we ended up
Where we are now
What might help us get better

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DKA

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A Bit of History – Pre Insulin

DKA was universally fatal
After the siege of Paris in 1870, it was realised

that strict diets could prolong life for a year or two

– As promoted by Fredrick Allen in the US and Bernard Naunyn in Germany (he was also amongst the first to advocated the use of alkali’s in ‘diabetic coma’)

Bliss M The discovery or insulin – 25th anniversary edition. University of Toronto Press. 2000

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A Bit of History – The Early Years

Between 1923 and 1925, Elliot Joslin reported that

31 out of 33 people he treated for DKA had survived

– But with very gentle parenteral fluid replacement

In the UK, RD Lawrence advocated aggressive

fluid replacement

– 3-6 pints over 1-2 hours – Given with adrenaline, stropanthin and a caffeine enema

Joslin EP et al Med Clin N Amer 1925;8:1873-1919 Lawrence RD Br Med J 1930;i(3614):690 Lawrence RD Br Med J 1936;ii(3940):81-82

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Fluids

Hence the start of the discussion about rate of

fluid replacement

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A Bit of History – The Early Years

In 1945, Howard Root in Boston reported how

mortality had dropped from 12% between January 1923 and August 1940 to 1.6% between August 1940 and May 1944

– 1923 to 1940, average insulin dose in the 1st 24 hours was 237 units – 1940 to 1944, average insulin dose in the 1st 24 hours was 287 units (range 50 to 1770)

Root HF JAMA 1945;127(10):557-564

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In 1948, Micks in Dublin advocated

– 100 units for those presenting in ‘pre-coma’ – 500 units for those in true coma and then 100 units intravenously every 15 minutes until there was signs

f improvement (‘doses of over 2000 units have

sometimes been required’)

A Bit of History – The Early Years

Micks RH Br Med J 1948;ii(4568):200-203

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A Bit of History – The Early Years

In 1949, Black and Malins reported a case series
f 170 consecutive cases treated with an

average of 265 units

– Mean of 265 units (140 to 500) of intravenous insulin for those ‘drowsy but rousable’ – Mean of 726 units (250 to 1400) for those ‘rousable with difficulty’ – Mean of 870 units (500 to 1400) for those ‘unconscious on admission’

Black AB & Malins JM Lancet 1949;253(6541):56-59

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Insulin

Hence the introduction of high dose insulin

infusions

– With ‘young and enthusiastic’ junior medical staff constantly by the patients’ bedside – A well equipped laboratory available 24 hours a day

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Low Dose Insulin

Page MM et al Br Med J 1974;ii(921):687-690 Semple PF et al Br Med J 1974;ii(921):694-698

Rate of glucose and β-OHB drop with low dose (5-6 units/hr) insulin infusion

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People Were Still Dying

Given 0.1u/kg/hr and 1-2 L of fluid on admission then 1 L every 3-4 hours,

and giving potassium 20-40mmol/hour

Carroll P et al Diabetes Care 1983;6(6):579-585

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So…

DKA was treated with

– Fluid – Intravenous insulin – Potassium – ± bicarbonate & phosphate

But how much and how fast?

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Danger

How do the order sets for DKA vary amongst

your local hospitals?

Are they the same or so they have minor

differences?

What about across Counties? Across States?
What effect on outcomes do these (minor)

differences have?

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Where Are We Now?

In 2010 the JBDS produced

a guideline on the management of DKA

With > 20,000 hard copies

given out or downloaded

http://www.diabetologists-abcd.org.uk/JBDS/JBDS.htm

An updated guideline was

published in late 2013

A national survey was

conducted in Autumn 2014

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Overall quality of JBDS – IP guidelines in 104 UK Trusts

DKA

Overall Quality of JBDS Guidelines

Data from Mike Sampson. Feedback from 104 hospitals - first shown at Diabetes UK March 2013

Over 90% of respondents rated the guidelines as ‘Excellent’ or ‘Good’

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Diagnostic Criteria - ADA and JBDS

Kitabchi AE et al Diabetes Care 2009;32(7):1335-1343 http://www.diabetologists-abcd.org.uk/JBDS/JBDS.htm

(200mg/dl)

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Marker of severity Value Marker of severity Value Mental status GCS<12 or abnormal APVU score Pulse <60 or >100 bpm Oxygen saturation <92% on air (assuming normal baseline) Urine output <0.5ml/kg/hr or AKI pH <7.1 Blood ketones >6.0mmol/l Potassium <3.5 or >6.0 mmol/l Bicarbonate <5.0mmol/l Systolic BP <90mmHg Anion gap >16.0mmol/l Kitabchi AE et al Diabetes Care 2009;32(7):1335-1343 http://www.diabetologists-abcd.org.uk/JBDS/JBDS.htm

Markers of Severity – ADA and JBDS

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A Question

How do we know that what we are doing is

correct?

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Where Are We Going?

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Results

283 forms were received from 72 hospitals

between May and November 2014

There are hundreds of messages in the data!
A few of the main ones are:

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Precipitants (%)

Dhatariya K et al Submitted for publication

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Fixed Rate Intravenous Insulin

The use of 0.1units/kg/hr led to excellent rises in

pH and bicarbonate – so DKA resolved by 18.77 hours

Dhatariya K et al Submitted for publication

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Potassium

But despite an aggressive potassium replacement

regimen – more than 50% of patients became hypokalaemic

Dhatariya K et al Submitted for publication

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Take Home Message

Despite the existence of widely adopted national

guidance – there are areas that need addressing

Has the slow evolution of the ‘evidence’ resulted

in ‘complacency’?

We need to make sure the guidance that we

give has a robust evidence base

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HHS

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Pasquel FJ, Umpierrez GE. Diabetes Care 2014;37(11):3124-3131

Julius Dreschfeld August W. Von Stosch Theodor Von Frerichs De Graeff y Lips

Sament y Schwartz

1828 1880 1880 1957

‘Diabetic Coma’ 1st Reports of HHS Treatment pre- and post-insulin

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First Mention in English?

On the 18th August 1886 by Dreschfeld in the

Bradshawe Lecture at the Royal College of Physicians of London

– Diabetic coma “though of small compass, is yet full of interest both to the physician and to the pathologist”

He described 3 types of coma

– Drowsiness, passing onto coma – An excited nervous system (resembling alcohol intoxication), then drowsiness and coma – Dyspnoea with acetone (the most frequent sort)

Dreschfeld J Br Med J 1886;ii(1338):358-363

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Prescience

He described the coma in those who did not

have acetone

– As occurring mainly in those over 40 – Who were stout and well nourished at the time of death – Fatty liver on necropsy

Dreschfeld J Br Med J 1886;ii(1338):358-363

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Early Mentions of Non Ketotic Diabetes

RD Lawrence in 1951

– Described ‘lipo-plethoric’ or ‘fat diabetics’ – And the rarer ‘lipo-atrophic’ or ‘thin diabetics’

This was associated with ‘intense lipidaemia’
Sament and Schwartz in 1957 describe a case

where 270 units of insulin reduced glucose from 1568mg/dl to 700mg/dl

– describing much greater insulin sensitivity compared to DKA

Lawrence RD BMJ 1951;1:373 Sament S S Afr Med J 1957;31(36):893-894

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Given 0.1u/kg/hr and 1-2 L of fluid on admission then 1 L every 3-4 hours,

and giving potassium 20-40mmol/hour

Carroll P et al Diabetes Care 1983;6(6):579-585

Continuing Mortality

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Evolution

Kitabchi AE et al Diabetes Care 2009;32(7):1335-1343

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Joint British Diabetes Societies for Inpatient Care

In August 2012 JBDS

published a national guideline on the management of HHS

http://www.diabetologists-abcd.org.uk/JBDS/JBDS.htm

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Overall quality of JBDS – IP guidelines in 104 UK Trusts

Overall Quality of JBDS Guidelines

Data from Mike Sampson. Feedback from 104 hospitals - first shown at Diabetes UK March 2013

HHS

Over 90% of respondents rated the guidelines as ‘Excellent’ or ‘Good’

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ADA and JBDS HHS Definitions

ADA (2009) JBDS (2012) Plasma glucose >600mg/dl (33.3mmol/l) >540mg/dl (30mmol/l) Arterial pH >7.3 >7.3 Serum bicarbonate >18mEq/l >15mmol/l Urine ketones Small Not referenced Serum ketones Small <3.0mmol/l Effective serum osmolality >320mOsm/Kg >320mOsm/Kg Anion gap Variable Not referenced Mental status Stupor / coma Not referenced

Kitabchi AE et al Diabetes Care 2009;32(7):1335-1343 http://www.diabetologists-abcd.org.uk/JBDS/JBDS.htm

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Do These Regimens Work?

No idea
Another national survey is needed!

Kitabchi AE et al Diabetes Care 2009;32(7):1335-1343 http://www.diabetologists-abcd.org.uk/JBDS/JBDS.htm

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In Summary

The management of DKA and HHS has come a

long way over the last 75 years

The evolution of treatment pathways has been

incremental and national guidelines have, to date, been consensus based

Evidence is needed to see if they do what we

want them to do

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Contributors to the UK DKA Survey

Addenbrookes Hospital, Sarah Finer, Lorreta Chindo, (5) Aintree University Hospital, Maureen Wallymahmed, (5) Alexandra Hospital, Redditch, Natalie Quine, (5) Antrim Area Hospital, Des Rooney, (5) Birmingham City Hospital, Brian C Lee, (5) Bronglais General Hospital, Aberystwyth, Adtunji Adeolu, (5) Bradford Royal Infirmary, Susana Gonzalez, (5) Bristol Royal Infirmary, Kiszy Locke, (5) Calderdale & Huddersfield NHS Foundation Trust, Rob Moisey Countess of Chester Hospital, David Ewins, (5) Craigavon Area Hospital, Una Bradley, (2) Derriford Hospital, Plymouth, Alex Baggott, (5) Diana, Princess of Wales Hospital, Grimsby, Steve Baines, (5) Dorset County Hospital, Andrew Macklin, (1) Friarage Hospital, North Yorkshire, Shafie Kamaruddin, (3) Frimley Park Hospital (5) George Eliot Hospital, Nuneaton , Joanne Wilson, (2) Gloucestershire Hospitals NHS Trust, Helen Giles, (5) Good Hope Hospital, Sutton Coldfield , Sharon Jones Harrogate District Hospital, Peter Hammond, (5) Hull Royal Infirmary, Belinda Allan, (5) James Cook University Hospital, Sath Nag James Paget University Hospital, Norfolk, Maya Venu (5) King’s Mill Hospital, Nottinghamshire , Sarb Sihota,(1) Leicester Royal Infirmary, Kath Higgins, (5) Luton & Dunstable University Hospital, Shiu-Ching Soo, (5) Musgrove Park Hospital, Taunton, Paul Lambert, (5) Nevill Hall Hospital, Monmouthshire, Fiona Smeeton, (5) Ninewells Hospital, Dundee, Theresa Torrance, (5) Nobles Hospital, Isle of Mann, Amutha Krishnan, (5) Norfolk and Norwich University Hospital, Michelle Tilbury, (5) North Middlesex University Hospital, Anukul Garg, (5) Northern Devon Healthcare NHS Trust, Pauline Budge, (5) Northumbria Healthcare NHS Foundation Trust , Asgar Madathil, (5) Perth Royal Infirmary, Theresa Torrance Peterborough City Hospital, Sampson Oyibo, (5) Pinderfields General Hospital, West Yorkshire, Ryan D'Costa, (3) Poole Hospital, Mike Masding Princess Royal Hospital, West Sussex, Karen Davies, (3) Queen Elizabeth Hospital, Birmingham , Punth Kempegowda, (5) Queen Elizabeth Hospital, Kings Lynn, V. Brindle, (5) Royal Albert Edward Infirmary, Wigan, Anne Ollerton, (3) Royal Bolton Hospital, Suzanne Palin, (5) Royal Bournemouth Hospital, Louise Curtis, (5) Royal Derby Hospital, Beverley Eaglesfield, (5) Royal Devon and Exeter Hospital, Aftab Aziz, (5) Royal Free Hospital, London, Nazia Rashid, (5) Royal Gwent Hospital, Newport, Priya Mohan Babu, (5) Royal Surrey County Hospital, Roselle Herring, (5) Royal Sussex County Hospital, Paul Grant, (5) Royal Victoria Hospital, Belfast (5) Royal Victoria Infirmary, Newcastle, Ashraff, (5) Salisbury District Hospital, Steve Nobbs, (5) Sandwell General Hospital, Brian Lee, (3) Singleton Hospital, Swansea , Jawad Bashir, (5) South Eastern Health and Social Care Trust, Ulster, Joan Calvert, (4) South Tyneside District Hospital, S. Ashraff, (5) St Mary's Hospital, Isle of Wight, Phil Mannall, (1) Sunderland Royal Hospital, Peter Carey The Royal Wolverhampton Hospitals NHS Trust, Jenny Dudley Torbay Hospital, Louise Williams, (5) University Hospital of North Staffordshire, Julie Wilkins, (5) University Hospital Southampton NHS Foundation Trust ,Ee-Lin Lim Victoria Hospital, Fife, Denise Burns, (5) Warrington & Halton Hospitals NHS Foundation Trust, Paula Chattington, (5) Watford General Hospital, Kieran Mullan West Suffolk Hospital, Mohamed Ashif Majeed, (5) Whiston Hospital, Sue Michaels, (5) Worcestershire Royal Hospital , L. Smith, (2) Wrexham Maelor Hospital , Anthony Dixon, (5) Yeovil District Hospital (5) Ysbyty Gwynedd, Teleri Vaughan-Evans, (5)

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