PAEDIATRIC ALTERED CONSCIOUS LEVEL GUIDELINE
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DELPHI PROCESS

Round one

13. Metabolic illness

Statement 13a

Hyperglycaemia

(i) Diabetic ketoacidosis can be diagnosed if all three of the following are present in a child with reduced consciousness:

A capillary or venous blood glucose of 11.0 mmol/l or more

A capillary or venous blood pH of less than 7.3

Ketones in the urine

% Agree	% Disagree	Result
84.8%	6.1%	Included

Position	Comments
Radiol	A + B yes; C no

(ii) If diabetic ketoacidosis is diagnosed, then follow the NICE guidelines on the management of type 1 diabetes.

% Agree	% Disagree	Result
96%	0%	Included

Position	Comments
ED P	We have our own guidelines
Paed	We have a pretty robust set of guidelines from our in house paediatric endocrinologists. I do not know how/if they vary from NICE guidelines
PICU	incorporated into local guideline practice

Hypoglycaemia

Statement 13b (Hypoglycaemia)

Hypoglycaemia (defined in statement 3b) in a child with an altered conscious level requires the following investigations to be taken during the hypoglycaemia episode: (these can all be requested from the samples agreed upon in statement 7e)

(i) plasma lactate

% Agree	% Disagree	Result
90%	0%	Included

Position	Comments
	Blood lactate taken during acute illness are often raised for many reasons and their value in these circumstances is doubtful
ED	May need treatment before investigation
Endo	Stem = with no history of diabetes

(ii) plasma ammonia

% Agree	% Disagree	Result
96.7%	3.3%	Included

Position	Comments
Metab	Only useful in organic acidaemias and in the Hyperammonaemia/hyperinsulinaemia syndrome
ED	I have no experience of ever doing this in A+E

(iii) plasma insulin

% Agree	% Disagree	Result
89.7%	0%	Included

Position	Comments
ED	I have no experience of ever doing this in A+E
Biochem	And C peptide

(iv) plasma cortisol

% Agree	% Disagree	Result
92.9%	0%	Included

Position	Comments
ED	I have no experience of ever doing this in A+E

(v) plasma growth hormone

% Agree	% Disagree	Result
78.3%	0%	Included

Position	Comments
ED	I have no experience of ever doing this in A+E
Metab	Growth hormone estimations taken during acute hypoglycaemia are very rarely usefu

(vi) acyl-carnitine profile (on Guthrie card or from stored frozen plasma)

% Agree	% Disagree	Result
75%	0%	Included

Position	Comments
Metab	Acyl carnitines on a Guthrie card should always be measured IN WHOLE BLOOD NOT Plasma because there is a risk of missing longer chain acylcarnitines
Neuro	I don’t think it needs to be during the hypoglycaemic episode itself
ED	I have no experience of ever doing this in A+E
PICU	NOT AS AN INITIAL INVESTIGATION
Neuro	Depends on age

(vii) plasma free fatty acids

% Agree	% Disagree	Result
81.8%	4.5%	Included

Position	Comments
ED	I have no experience of ever doing this in A+E

(viii) plasma beta-hydroxybutyrate

% Agree	% Disagree	Result
91.3%	4.3%	Included

Position	Comments
ED	I have no experience of ever doing this in A+E
Endo	Urinary ketones

(xi) galactose-1-phosphate uridyl transferase level

% Agree	% Disagree	Result
26.1%	34.8%	Excluded

Position	Comments
Paed	Depends on age of child
ED	I have no experience of ever doing this in A+E
Metab	Hypoglycaemia is only very rarely a feature of galactosaemia despite what textbooks might say. Should be done is there is significant liver disease
Neuro	Not during the episode
ED P	In neonates. Depends on clinical features
Biochem	If galactosaemia is being considered most important criteria is that the child has not had a transfusion
Renal	Not necessary when hypoglycaemic
Endo	?just in infancy
Neuro	Depends on age of child

(x) urine organic acids profile

% Agree	% Disagree	Result
85.2%	0%	Included

Position	Comments
ED	I have no experience of ever doing this in A+E

(xi) urine orotic acid

% Agree	% Disagree	Result
55%	0%	Excluded

Position	Comments
Neuro	not sure
Renal	Hyperammonaemia investigation
Metab	Only indicated if there is hyperammonaemia
ED	I have no experience of ever doing this in A+E
Biochem	Test not necessary on all cases. May be detected as part of organic acid profile

(xii) urine amino acids profile

% Agree	% Disagree	Result
70.4%	7.4%	Discussed in round 2

Position	Comments
ED	I have no experience of ever doing this in A+E
Biochem	??Plasma amino acids

(xiii) urinary non-glucose reducing substances

% Agree	% Disagree	Result
61.5%	15.4%	Excluded

Position	Comments
ED	I have no experience of ever doing this in A+E

Statement 13c

(i) The emergency treatment of hypoglycaemia in a child with a reduced conscious level is a bolus of 5 ml/kg of 10% dextrose solution

% Agree	% Disagree	Result
81.8%	12.1%	Discussed in round 2

Position	Comments
Metab	child: glucose 10% 2mL/kg bolus IV, then 0.1mL/kg/minute, until fully conscious
Paed	WE use 2ml/kg and then repeat if glucose still low
Metab	we recommend 2ml/kg 10% dextrose
Metab	The dose of glucose is too high. Te normal requirement in young children is 6-8mg/kg/min. A standard dose should be 2ml (200mg)/kg of 10% glucose followed by a glucose infusion at the maintenance rate. Otherwise there is a risk of triggering further release of insulin in hyperinsulinaemic patients.
Metab	2 ml/kg, then an infusion
Renal	I thought it was less – 3-4 ml/kg
PICU	define duration of bolus – I would give over 10 mins

(ii) An infusion of 10% dextrose solution should be administered to maintain the blood glucose between 4 and 7 mmol/l

% Agree	% Disagree	Result
88.2%	2.9%	Included

Position	Comments
ED	Depends on response to bolus

(iii) Hypoglycaemia is not a diagnosis in itself, therefore urgent support from an endocrinologist and metabolic medicine physician should be obtained to determine the subsequent management

% Agree	% Disagree	Result
77.1%	8.6%	Included

Position	Comments
Neuro	Initial investigations can be done by the attending paediatrician
ED P	Unless clear cut
ED P	May need support but not necessarily urgently. Could wait several hours or until the next day if middle of the night
Paed	person with an interest will do
Neuro	Needs to reflect local policy
Biochem	Seek advice from laboratory metabolic biochemists to aid further sampling and investigations
Endo	Treatment with glucose urgent, not necessarily an endocrinologist (if samples required listed and sent to lab urgently)
PICU	most would accept wait for response … which is usually ggod. If recalcitrant need advice
Paed	As soon as practical but departmental guidelines should suffice for 24-48 hours

Hyperammonaemia

Statement 13d

A plasma ammonia level of 200 micromol/l is significantly raised and needs actively treating

% Agree	% Disagree	Result
85.2%	7.4%	Included

Position	Comments
Metab	Strictly the comment should be ‘needs actively investigating.
PICU	Age of child?
ED P	Treatment is usually given when the plasma ammonia is much higher as a moderately raised level can be due to other causes. This is my understanding with patients we have had before. I am not aware is the level at which we treat plasma ammonia has gione down, and this comment affects the answers to many of the other questions in this section
Metab	“active treatment” (sp)

Statement 13e

If the plasma ammonia level is above 200 micromol/l, then the following investigations need to be sent and reviewed: (these can all be requested from the samples agreed upon in statement 7e)

(i) blood gas

% Agree	% Disagree	Result
96.2%	0%	Included

Position	Comments
Renal	Hopefully this would have been sent anyway!

(ii) plasma amino acids profile

% Agree	% Disagree	Result
96.2%	0%	Included

(iii) urinary amino acids profile

% Agree	% Disagree	Result
88.5%	3.8%	Included

(iv) urinary organic acids profile

% Agree	% Disagree	Result
100%	0%	Included

(v) urinary orotic acid

% Agree	% Disagree	Result
94.7%	0%	Included

Position	Comment
Biochem	Not required on all patients. Results of other investigations will determine whether necessary

(vi) liver function tests - aspartate transaminase/alanine transaminase, alkaline phosphatase, albumin/protein

% Agree	% Disagree	Result
100%	0%	Included

Position	Comments
Renal	Usually part of an organic acid screen anyway I think

(vii) Coagulation studies – activated partial thromboplastin time, prothrombin time, fibrinogen, fibrinogen degredation products

% Agree	% Disagree	Result
96%	0%	Included

Statement 13f

(i) A plasma ammonia level of 200 micromol/l needs actively reducing by starting a sodium benzoate infusion

% Agree	% Disagree	Result
80%	10%	Included

Position	Comments
Metab	“active reduction” (sp)
Neuro	Level is too low
Renal	I think it should first be repeated urgently given problems with artefactually high levels from poor sampling
ED P	Treatment is usually given when the plasma ammonia is much higher as a moderately raised level can be due to other causes. This is my understanding with patients we have had before. I am not aware is the level at which we treat plasma ammonia has gione down, and this comment affects the answers to many of the other questions in this section
Neuro	Seek expert advice, but generally yes
Paed	Would seek urgent advice before commencing
Paed	I would discuss Mx with a metabolic team asap

(ii) Sodium benzoate should be given with a loading dose of 250 mg/kg (diluted in 15ml/kg of 10% dextrose) over 90 minutes

% Agree	% Disagree	Result
91.7%	8.3%	Included

Position	Comments
Neuro	Need to consider whether per kg doses are appropriate in older adolescents
PICU	WOULD NEED TO LOOK IT UP
Paed	Would seek urgent advice before commencing
ED P	90-120 mins
Metab	I use 30ml/kg as the volume, and 5% glucose. Hyperglycaemia is common after more than this amount of glucose over 90 mins
Metab	Sodium benzoate can be given as a 2% solution and more concentrated if necessary if there is a need for fluid restriction
Endo	Need to look it up!
Metab	Should be given quicker – over 20 minutes

(iii) After the loading dose, a further infusion of sodium benzoate 250 mg/kg (diluted in 15ml/kg of 10% dextrose) should be administered over 24 hours

% Agree	% Disagree	Result
90%	0%	Included

Position	Comments
Paed	Would seek urgent advice before commencing
Neuro	Specialist advice needed
Metab	Again, I use 30ml/kg, this time as 10% glucose
PICU	AS ADVISED BY METABOLIC TEAM
Metab	Depends on the initial response
ED P	I’m unsure about the recommended length of treatment
Endo	Need to look it up

(iv) A plasma ammonia level of 200 micromol/l needs actively reducing by starting a sodium phenylbutyrate infusion of 500 mg / kg (diluted in 25 ml/kg of 10% dextrose) administered over 24 hours

% Agree	% Disagree	Result
50%	12.5%	Discussed in round 2

Position	Comments
Metab	Can be use if sodium benzoate not available but at a lower dose
ED P	I think we treat much higher levels Treatment is usually given when the plasma ammonia is much higher as a moderately raised level can be due to other causes. This is my understanding with patients we have had before. I am not aware is the level at which we treat plasma ammonia has gone down, and this comment affects the answers to many of the other questions in this section
Paed	Would seek urgent advice before commencing
Neuro	Specialist advice needed
Metab	Put a don’t know here because SPB is contraindicated in some disorders. I will use this only where I know the diagnosis is a UCD, and not for Reye syndrome, organic acidaemias
Metab	The dose is relatively high for a plasma ammonia of 200 mcmol/l. It is usual to start with sodium benzoate and add sodium phenylbutyrate. An algorithm would be useful here
Endo	Would need to D/W metabolic consultant but may need to be added
Metab	“active reduction” (sp). Unclear which drug is better in acute situation…

(v) A plasma ammonia level above 200 micromol/l for six hours despite treatment requires emergency haemodialysis

% Agree	% Disagree	Result
46.7%	6.7%	Discussed in round 2

Position	Comments
Paed	Would seek urgent advice before commencing
Neuro	Specialist advice needed
Metab	depends on how high the level is – dialysis may be necessary immediately
PICU	Context?
Metab	Tend to agree. This is tricky. Might set the dialysis a bit higher, at 350umol/l
PICU	ONLY IF OTHER MEASURES DO NOT DROP AMMONIA QUICKLY
Endo	Depends on whether improving or not
Metab	It would depend on the values ( ?205 or 499!) and the change in 6 hours as well as the patients general condition

(vi) A plasma ammonia level above 500 micromol/l requires emergency haemodialysis and transfer should be arranged urgently, whilst starting the ammonia reducing treatments available locally

% Agree	% Disagree	Result
95%	5%	Included

Position	Comments
ED P	I would take advice from a metabolic unit
Metab	cutoff should be lower – 350 or 400micromol/l–
Paed	Would seek urgent advice before commencing
Neuro	Specialist advice needed

(vii) As soon as a plasma ammonia level of 200 micromol/l or above is detected, contact the nearest metabolic medicine centre for advice

% Agree	% Disagree	Result
96.2%	0%	Included

Position	Comment
Biochem	Important to confirm the high ammonia level on a repeat specimen

(viii) As soon as a plasma ammonia level of 200 micromol/l or above is detected, contact the nearest paediatric dialysis centre and arrange transfer for potential haemodialysis, whilst starting the ammonia reducing treatments available locally

% Agree	% Disagree	Result
47.8%	30.4%	Excluded

Position	Comments
PICU	CAN BE DONE ON INTENSIVE CARE UNIT
Paed	Would seek urgent advice before commencing
Metab	depends on exact level
Renal	Very few centres currently do haemodialysis for hyperammonaemia. The person to contact initially is the intensivist
ED P	Take advice from metabolic unit first
Neuro	Depends on local availability and response to treatment
Endo	Depends on advice from metabolic centre
PICU	should occur in PICU

Catabolic state

Statement 13f

(i) A child with a reduced conscious level, a capillary/venous pH < 7.3 and with ketones in the urine is in a catabolic state

% Agree	% Disagree	Result
75.9%	0%	Included

Position	Comments
Metab	Could have a metabolic disorder!
PICU	a reasonable definition broadly of catabolic state

(ii) Any child in a catabolic state not caused by diabetic ketoacidosis should have the following investigations requested: (these can all be requested from the samples agreed upon in statement 7e)

(a) plasma lactate

% Agree	% Disagree	Result
89.7%	3.4%	Included

(ii) Any child in a catabolic state not caused by diabetic ketoacidosis should have the following investigations requested: (these can all be requested from the samples agreed upon in statement 7e)

(b) plasma ammonium

% Agree	% Disagree	Result
93.1%	0%	Included

(c) plasma amino acids

% Agree	% Disagree	Result
89.3%	0%	Included

(d) liver function tests - aspartate transaminase/alanine transaminase, alkaline phosphatase, albumin/protein

% Agree	% Disagree	Result
92.9%	0%	Included

(e) urinary amino acids profile

% Agree	% Disagree	Result
82.8%	3.4%	Included

(f) urinary organic acids profile

% Agree	% Disagree	Result
92.9%	0%	Included

(iii) For any child in a catabolic state not caused by diabetic ketoacidosis, advice should be obtained urgently from the nearest metabolic medicine unit

% Agree	% Disagree	Result
75.9%	3.4%	Included

Position	Comments
ED P	Depends on the situation as a hypovolaemic child with starvation can present in this way
Neuro	Depends on local availability?
Endo	When more information available
PICU	if cause unclear

(iv) A child with a reduced conscious level who is in a catabolic state needs treating by following the algorithm below:

pH	Blood glucose (mmol/l)	Urinary ketones	Treatment
7.0 – 7.29	4.0 – 11.0	+++	Treat shock Infuse 10% dextrose at 100 % of maintenance fluid requirements with 20 – 40 mmol NaCl (30%) added per litre If blood glucose increases to above 11 mmol/l then start insulin infusion 0.05 U/kg/hr (aiming to keep blood glucose between 6.0 and 10.0 mmol/l)
7.0 – 7.29	> 11.0	+++	Treat shock Follow diabetic ketoacidosis guideline

% Agree	% Disagree	Result
43.8%	18.8%	Excluded

Position	Comments
Metab	Would recommend a higher sodium intake, at least 75mmol/l, if not 150mmol/l initially
ED P	I do not routinely manage these patients like this- it would depend on what I felt the cause of this situation to be
Paed	Never seen this before ?evidence
Endo	But need a standard solution of 10% dextrose and saline

(v) A child with a reduced conscious level who is in a catabolic state needs treating by following the algorithm below: (please note this table is a continued from the previous statement)

pH	Blood glucose (mmol/l)	Urinary ketones	Treatment
< 7.0	4.0 – 11.0	+++	Treat shock Infuse 10% dextrose at 150 % of maintenance fluid requirements with 20 – 40 mmol NaCl (30%) added per litre Start insulin infusion 0.05 U/kg/hr (aiming to keep blood glucose between 6.0 and 10.0 mmol/l)
< 7.0	> 11.0	+++	Treat shock Follow diabetic ketoacidosis guideline

% Agree	% Disagree	Result
40%	20%	Excluded

Position	Comments
Metab	Too aggressive, increases risk of raised ICP, cerebral oedema
PICU	I found these algorithms difficult to follow
ED P	I do not routinely manage these patients like this- it would depend on what I felt the cause of this situation to be
Paed	Never seen this before ?evidence
Endo	Feel uneasy about 150% fluids. ?15% dextrose

(vi) Children in a catabolic state are at risk of raised intracranial pressure, therefore careful monitoring is required with the large fluid volume administration

% Agree	% Disagree	Result
81.8%	0%	Included

Position	Comments
PICU	but important to treat shock
PICU	CVP measure 1^st. consider ICP

(vii) Lactate levels need to be carefully monitored during 10% dextrose infusion

% Agree	% Disagree	Result
64.7%	0%	Excluded

(viii) If lactate levels rise above 15 mmol/l obtain urgent advice from the nearest metabolic medicine unit

% Agree	% Disagree	Result
91.7%	4.2%	Included

Position	Comment
Biochem	May be metabolic lab
PICU	care with sampling

(ix) If lactate levels are persistently high despite treatment for hypoxia and shock discuss with the nearest metabolic unit the need for an urgent skin and muscle biopsy

% Agree	% Disagree	Result
72%	8%	Excluded

Position	Comments
ED P	I would be directed by the metabolic team
Neuro	Don’t know what you mean by urgent
Metab	Other investigations e.g. acylcarnitines & urine organic acids more helpful in the acute situation
Biochem	“further investigation” NOT “an urgent skin and muscle biopsy”
PICU	management in general

Statement 13g

(i) A child in a catabolic state will need nutrition restarted early to prevent further catabolism

% Agree	% Disagree	Result
92.6%	0%	Included

(ii) A child in a catabolic state will need dietetic input on the first day of admission

% Agree	% Disagree	Result
70.4%	14.8%	Excluded

Position	Comments
PICU	After treating shock and no concerns regarding gut perfusion
Neuro	Early on