Encephalopathy following diabetic ketoacidosis in a type 1 diabetes patient – docslide.com.br severe anoxic brain injury


76 pract diab int march 2010 vol. 27 no. 2 copyright © 2010 john wiley sons


Hyperglycaemic emergencies and

Specifically diabetic ketoacidosis are

Common and treated, at least

Initially, by physicians who are not

Necessarily specialised in the field of

Diabetes. Various clinical protocols

Are utilised with variable success.

Many metabolic derangements occur

Simultaneously and, together with

Patient factors, make the restoration

Of metabolic balance challenging.

Complications can surface rapidly

And in mysterious ways, requiring

Astuteness on behalf of the acute

Physician in order to avoid long-term

Irreversible damage.

Case history

A 44-year-old gentleman with type I

Diabetes mellitus was transferred to

severe anoxic brain injury

Our emergency department after hav-

Ing been found collapsed in his home

With a glasgow coma score (GCS) of

11/15. His sister alerted the authori-

Ties after not having heard from him in

Three days. The police and ambulance

Service found him semi-comatose in

His flat. There was no evidence of

Alcohol or drugs at the scene.

Collateral history from his sister

And family doctor revealed that the

Patient had had diabetes for 16 years

With a most recent hba1c of 7.6%.

He was on a basal bolus regimen of

Insulin and did not have any other

Co-morbidities. He had suffered from

Recurrent hypoglycaemic episodes

Including two emergency hospital

Admissions in the previous three years

For severe hypoglycaemia precipitated

By alcohol binges.Severe anoxic brain injury due to depression

He had recently lost his job as a

Computer analyst. He lived alone,

There was no history of any aggressive

Behaviour and he was known to be

Always very polite and pleasant.

On arrival he was unwell with

Kussmaulâs breathing, tachycardic at

115bpm, BP 134/76mmhg, with signs

Of dehydration. Systemic examination

Did not reveal signs of sepsis and there

Were no focal neurological findings.

Initial investigations revealed acute

Renal failure and a metabolic acidosis

With a ph of 7.07, PCO2 1.6, PO2 20.1,

HCO3 3.5, lactate 4.5. Serum sodium

Ranged between 143 and 146mmol/L,

And serum phosphate between 0.80

And 0.86mmol/L during his acute

Illness. Liver and bone profiles were

Normal. Urine dipstick was strongly

severe anoxic brain injury

Positive for ketones and the serum

Glucose was 36mmol/L. Initial treat-

Ment was with intravenous 0.9%

Saline, soluble insulin and potassium

Replacement as per hospital protocol

For the treatment of diabetic keto –

Acidosis. Within 36 hours he received

5L of 0.9% saline followed by 4L of

5% dextrose, all bags containing

Potassium. He was transferred to

The high dependency unit where his

Fluid and acid-base balance was moni-

Tored closely.

Within 24 hours into his admis-

Sion the initial metabolic derange-

Ment was reversed but his GCS

Remained low at 11/15. CT scan of

The head performed 16 hours after

Admission was completely normal and

A lumbar puncture did not reveal any

Evidence of meningitis (opening pres-

Sure 21cm H2O, no red or white

severe anoxic brain injury

Blood cells, glucose 12.1mmol/L and

Protein 51mg/dl). Microbiology cul-

Tures and toxicology for recreational

Drugs, alcohol, paracetamol and sali-

Cylate were all negative. In view of his

Previous hospital admissions, intra-

Venous thiamine was administered for

Three days followed by an oral course.

Over the following five days his

Drowsiness gradually resolved but

Was replaced by an uncharacteristic

Verbally and physically aggressive

Behaviour towards the nursing and

Medical staff. The patient had to be

Restrained by hospital security on a

Number of occasions and, reluctantly,

Antipsychotics were administered to

Encephalopathy following diabetic

Ketoacidosis in a type 1 diabetes patient

AD miras*, H ward


severe anoxic brain injury

A 44-year-old gentleman with type 1 diabetes mellitus was found collapsed with diabetic

Ketoacidosis. Following correction of the metabolic derangements his level of

Consciousness improved but he became encephalopathic, exhibiting unprecedented

Aggression with non-specific neurological signs. This profound neurological state persisted

For one month. Reversible causes of encephalopathy were investigated and excluded. The

Patient made a slow and almost complete recovery over a period of six months.

Encephalopathy is an unusual complication of hyperglycaemic emergencies with

Poorly understood underlying mechanisms. This case demonstrates the importance of

Considering and treating the numerous reversible causes of an encephalopathic state

severe anoxic brain injury

Before attributing altered levels of consciousness to the acute metabolic disturbances

Only. Copyright © 2010 john wiley sons.

Practical diabetes int 2010; 27(2): 76â78


Type 1 diabetes; encephalopathy; hypophosphataemia; thiamine deficiency;


Dr alexander dimitri miras, MRCP, bsc,

Specialist registrar in endocrinology and


Dr helen ward, MRCP, phd, consultant in

Endocrinology and diabetes

St peterâs hospital, chertsey, UK

*correspondence to: dr alexander dimitri

Miras, MRCP, bsc, specialist registrar in

Endocrinology and diabetes, st peterâs

Hospital, guildford road, chertsey KT16

0PZ, UK; e-mail: a.Miras@boltblue.Com

Received: 9 december 2008

Accepted in revised form: 2 july 2009

severe anoxic brain injury


Encephalopathy following diabetic ketoacidosis

Facilitate basic nursing care. His family

Were surprised and upset by his

Unprecedented and fluctuating

Aggression and confusion even though

In their presence their intensity was

Ameliorated. Neurological examina-

Tion at this stage revealed a slow,

Stuttering speech, automation, lip

Flickering and a persistent non-painful

Penile erection. No ophthalmoplegia

Or cerebellar signs were observed. MRI

Of the brain at this stage was entirely

Normal with no evidence of pontine

Myelinolysis. An electroencephalo-

Gram showed slow wave activity, gener-

Alised in the theta and delta range con-

Sistent with an encephalopathy (figure

1). Other causes of an encephalo-

severe anoxic brain injury

Pathic state were considered and

Subsequently excluded (table 1).

A month after his admission, his

Aggressive behaviour gradually

Regressed. The patientâs short- and

Long-term memory improved and he

Was eventually orientated in time,

Place and person. His speech and

Higher mental functions were still

Impaired. He was transferred to a

Local neuropsychiatric rehabilitation

Facility where he stayed for a month.

Six months following his presentation,

He has returned home and has now

Started to manage his finances with

The help of family and social services,

But remains irritable and his speech is

Still slow.


Encephalopathy precipitated by

Hyperglycaemic emergencies is

Described in the literature but the

Underlying mechanisms are poorly

severe anoxic brain injury

Understood.1 the metabolic derange-

Ments that occur during diabetic

Ketoacidosis/hyperosmolar hypergly-

Caemic state can produce a very

Similar clinical picture.1 in addition,

There are a number of potential

Confounding factors, such as the use

Of drugs and alcohol prior to

Presentation, variability in protocols

And practice for the treatment of

Adult hyperglycaemic emergencies

And coincidental presentation of

Encephalopathy due to another cause

In a patient with diabetes with second-

Ary metabolic disturbance.

Megarbane et al.1 implicate

Hypophosphataemia as a precipitant

For encephalopathy post diabetic

Ketoacidosis and treatment of this

Results in progressive and complete

Recovery. Hypophosphataemia is a

Very common electrolyte disturbance

severe anoxic brain injury

Following treatment of diabetic

Ketoacidosis being caused by phos-

Phaturia, which is a direct effect of

Serum acidosis and is worsened by a

Shift of phosphate together with glu-

Cose into the cells during treatment.

Reduced levels of red blood cell

2, 3 diphosphoglycerate may reduce

The amount of oxygen delivered to

The brain among other organs and

Precipitate encephalopathy. Our

Patientâs phosphate levels did drop to

A value of 0.26mmol/L (normal

Range 0.80â1.40mmol/L) two days

Into his admission. However, his

Encephalopathic state preceded this

Derangement despite improvements

In ph and ketonuria and no clinical

Improvement was observed with

Correction of hypophosphataemia.

A very interesting report by clark et

severe anoxic brain injury

Al.2 highlights the importance of

Acute thiamine deficiency in diabetic

Ketoacidosis. Malnutrition, osmotic

Diuresis, insulin deficiency and even

Insulin administration can all deplete

The bodyâs thiamine stores. Neuronal

Damage caused by thiamine deficiency

Affects specific vulnerable regions in

Animal models including the thala-

Mus, inferior colliculus, mammillary

Body, medial geniculate nucleus and

Medial vestibular nucleus. The patho-

Physiological mechanisms behind

This neuronal insult include cellular

Endothelial dysfunction directly

Caused by lack of thiamine and low

Levels of brain neurotransmitters

Including GABA, glutamate and

Serotonin which rely on thiamine for

Their production. Due to the previous

severe anoxic brain injury

Admissions with alcohol related

Hypoglycaemia our patient received

Early replacement with intravenous

Thiamine without any apparent impact

On the course of his encephalopathy.

Alcohol induced hypoglycaemia is

Well described and a well known

Danger in diabetic patients. Excessive

Alcohol intake reduces gluconeo –

Genesis and subsequently intestinal

Pract diab int march 2010 vol. 27 no. 2 copyright © 2010 john wiley sons 77

Figure 1. Electroencephalogram showing diffuse slow activity of approximately

4.5Hz (normal 8â13hz). (reproduced courtesy of dr adrian J fowle, FRCP,

BSc, consultant clinical neurophysiologist, st peterâs hospital, chertsey, UK)

Table 1. The following tests were

Either negative or the results were in

severe anoxic brain injury

The normal reference range

¢ HIV serology

¢ syphilis serology

¢ hepatitis B and C, CMV, EBV


¢ CSF viral serology

¢ short synacthen test

¢ serum lead

¢ serum caeruloplasmin/urinary


¢ serum ammonia

HIV = human immunodeficiency virus;

CMV = cytomegalovirus; EBV = epsteinâ

Barr virus; CSF = cerebrospinal fluid.


Encephalopathy following diabetic ketoacidosis

Absorption and glycogenolysis.3 brain

Tissue is selectively vulnerable to the

Resultant hypoglycaemia with the

Cortex, basal ganglia, substantia nigra

And hippocampus most commonly

Affected. Initial MRI changes include

Hyperintensity and hypointensity on

T1 and T2 weighted images followed

By diffuse brain oedema and atrophy

In the more severe cases.4 looking

severe anoxic brain injury

Retrospectively at our patientâs pres-

Entation, it is possible that he

Suffered a hypoglycaemic episode

Followed by rebound hyperglycaemia

With keto acidosis due to subsequent

Omission of insulin. Mild hypo –

Glycaemia induced cerebral lesions

Cannot be detected by MRI or CT;

However, his encephalopathy was so

Profound and persistent that radio-

Logical changes might be expected

To be observed and, interestingly,

Were not.

Therefore, we postulate that our

Patient suffered from a non-specific

And reversible encephalopathy

Related to diabetic ketoacidosis. To

This day, after careful investigation

Into the events leading to his

Presentation and in patient manage-

Ment and extensive searches of the

Medical literature, we have been

severe anoxic brain injury

Unable to pinpoint a clear cause for

Encephalopathy, apart from diabetic

Ketoacidosis. We present this case to

Raise awareness among the medical

Profession of the early identification

And treatment of reversible causes of

An encephalopathic state in future

Patients. If this proves difficult, all

Efforts during patient recovery

Should be focused on the avoidance

Of hypoglycaemia and on multi –

Disciplinary involvement of highly

Skilled staff for optimum outcome.

Conflict of interest statement

There are no conflicts of interest.


References are available at www.


Key points

¢ diabetic ketoacidosis is a common medical emergency causing multiple

And complex metabolic derangements

severe anoxic brain injury

¢ encephalopathy following treatment of diabetic ketoacidosis is rare and its

Mechanisms poorly understood

¢ acute physicians should consider the various causes of an acute

Encephalopathy â including hypoglycaemia, hypophosphataemia, thiamine

Deficiency, hypoadrenalism, alcohol excess, cerebral oedema and infections

 and treat them when possible

¢ diabetic ketoacidosis per se can cause an encephalopathic state

Without a single identifiable cause. The involvement of a multidisciplinary

Team and caution in avoiding hypoglycaemia are crucial for optimum

Long-term outcome


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Encephalopathy following diabetic ketoacidosis


1. Megarbane B, guerrier G, blancher

A, et al. A possible hypophos-

Phataemia induced life threatening

severe anoxic brain injury

Encephalopathy in diabetic keto –

Acidosis. Am J med sci 2006; 6:


2. Clark JA, burny I, sarnaik AP, et al.

Acute thiamine deficiency in diabetic

Ketoacidosis: diagnosis and manage-

Ment. Pediatr crit care med 2006;

7(6): 595â599.

3. Jain H, beriwal S, singh S. Alcohol

Induced ketoacidosis, severe hypo-

Glycemia and irreversible enceph-

Alopathy. Med sci monit 2002; 8(11):


4. Fujioka M, okuchi K, hiramatsu K-I,

Et al. Specific changes in human brain

After hypoglycaemic injury. Stroke

1997: 28: 584â587.

Pract diab int march 2010 vol. 27 no. 2 copyright © 2010 john wiley sons 78i