Patrick
B Mark1 , Tim Gordon-Walker1, Sarah Cooper2,
Jack Winter3
1.
Renal Unit, Western
Infirmary, Dumbarton Road Glasgow
2.
Institute of Neurological
Sciences, Southern General Hospital, Govan Road, Glasgow
3.
Department of
Gastroenterology, Gartnavel General Hospital, Great Western Road,
Glasgow
Correspondence
to:
Dr. Patrick Mark, Renal Unit, Western Infirmary,
Glasgow G11 6NT, UK.
E-Mail: p.mark@clinmed.gla.ac.uk
SMJ 2006 51(3): 50
Keywords:
Ammonia, Ureterosigmoidostomy, Encephalopathy, Haemodialysis
Metabolic complications including metabolic acidosis following ureterosigmoidostomy are common, but coma is rare. We describe a case of a 59 year old lady with recurrent coma, presenting many years following ureterosigmoidostomy. Serum ammonia levels during coma were grossly elevated at 327μmol/L (normal range 10-35 μmol/L). Successful treatment was instigated with haemodialysis and colonic irrigation, leading to normalisation of serum ammonia levels and concurrent restoration of normal consciousness. We advocate increased vigilance for this rare cause of coma in patients with a history of urinary diversion surgery.
A
59 year old female was admitted to our hospital with unexplained decreased
conscious level. On admission to accident and emergency her Glasgow Coma Score
was 5/15, with no localizing neurological signs. She was hypotensive (blood
pressure 75/30mmHg) and tachycardic (110 beats per minute). Other than an old
midline laparotomy scar there were no other positive findings on clinical
examination. There was no clear preceding illness and systemic enquiry taken
from her daughter added nothing to her recent history.
Her past medical history included reimplantation of both ureters into the sigmoid colon following a childhood road traffic accident. Her early adult life had been medically unremarkable but in 1993 she was admitted with unexplained confusion, which responded to rehydration. Over the next 12 years, she was admitted on a further 4 occasions with reduced consciousness, twice requiring ventilation in the intensive care unit. On each occasion she was noted to have a hyperchloraemic (normal anion gap) metabolic acidosis in keeping with previous ureterosigmoidostomy. During each admission her condition improved spontaneously with a combination of rehydration, broad spectrum antibiotics and intravenous sodium bicarbonate therapy and no conclusive diagnosis was made. Brain imaging with computed tomography (CT) and cerebrospinal fluid analysis were consistently normal during these admissions. Electroencephalogram (EEG) during these episodes of illness was compatible with a metabolic encephalopathy. Other past medical history included hypertension and drug therapy on admission was thiamine, enalapril, simvastatin, bendroflumethiazide and oral sodium bicarbonate.
On
this admission routine haematology was normal, biochemical profile revealed
sodium 145mml/L, potassium 3.9mmol/L, chloride 112mmol/L, bicarbonate 15mmol/L
Urea 7.5mmol/L and creatinine 74 µmol/L. Arterial
blood gases showed hydrogen ion 33mmol/L,
pO2 26kPa (on 28% Oxygen) and pCO2 3.72kPa. Liver
function tests and C-reactive protein were within the normal reference range.
Blood cultures were negative, repeat CT brain showed no intracranial abnormality
and EEG showed diffuse slowing in keeping with a metabolic encephalopathy. A
provisional diagnosis of metabolic encephalopathy with a partly compensated
normal anion gap metabolic acidosis was made, but despite 24 hours of therapy
with intravenous 1.26% sodium bicarbonate therapy and biochemical improvement in
her acid-base status, she remained comatose with a Glasgow coma score (GCS) of
5/15. At this point serum ammonia was measured and found to be grossly elevated
at 327μmol/L
(normal range 10-35 μmol/L),
therefore confirming a diagnosis of hyperammonaemic encephalopathy.
Haemodialysis
was commenced via a left internal jugular venous catheter (blood flow 200ml/min,
dialyzer Baxter Dicea 210, dialysate flow rate 500ml/min) to enable clearance of
serum ammonia and colonic irrigation was performed. During dialysis,
prophylactic parenteral B vitamins were given concurrently with intravenous
dextrose to prevent precipitation of a Wernicke’s encephalopathy and both
calcium and potassium were added to the dialysate to prevent hypocalcaemia or
hypokalaemia respectively. She was treated with four 4-hour haemodialysis
sessions (see Figure 1) and serum
ammonia returned towards normal. This was associated with a dramatic improvement
in her conscious level back to GCS 15/15 within 36 hours and normal cognition
was restored 48 hours after commencement of dialysis treatment. A low protein
diet and oral lactulose were instigated. The patient’s daughter has been given
a letter to advise medical staff to measure serum ammonia level in the event of
future presentation with coma. Revision to an ileal conduit is being considered.
Hyperammonaemic
encephalopathy is a recognised but rare complication following
ureterosigmoidostomy
(1-3)
. Following
this procedure, urine is drained into the sigmoid colon and then excreted at
defecation. More common complications include recurrent pyelonephritis, faecal
incontinence, hyperchloraemic metabolic acidosis and a
predisposition to colon cancer due to nitrosamine formation in the bowel.
Of note our patient had a normal colonoscopy in 1998, during a previous
admission with coma. Increased production of ammonia occurs in the colon due to
ureolysis due to urea splitting bacteria (e.g. Proteus mirabilis), and ammonia
is subsequently rapidly absorbed via the permeable colonic mucosa. Ammonia is
metabolized by the hepatic urea cycle, but this may be overwhelmed and coma
ensues, akin to hepatic encephalopathy. The risk of hyperammonaemia is increased
by constipation leading to prolonged colonic absorption of ammonia, and while
coma can ensue in the presence of normal liver function (as in our patient),
hepatic dysfunction may further increase the risk of the development of coma.
Hyperammonaemic coma has also been reported in patients with an ileal conduit
(4)
but appears
to be more common following ureterosigmoidostomy. This increased risk with
ureterosigmoidostomy is presumably due to the longer segment of bowel mucosa
exposed to urine.
In
addition to supportive measures the treatment of hyperammonaemic coma should
include removal of ammonia from the plasma by repeated haemodialysis, reduction
in ammonia production by colonic washout and broad spectrum antibiotics, and
measures to prevent recurrence in the future.
Ammonia
is a small molecule (molecular weight 17 daltons) without significant protein
binding and therefore is readily removed by haemodialysis. It is important to be
aware that serum ammonia concentration will rise after each dialysis session due
to delayed ammonia shifts from cells to plasma and continued colonic ammonia
production and absorption. Repeated sessions of haemodialysis will be required.
Haemodialysis has also been used successfully to treat hyperammonaemia in
the presence of urea cycle disorders
(5-7)
. Furthermore
the molecular adsorbent
recirculating system (MARS),
which has been used with some success in selected cases of liver failure,
incorporates an inbuilt dialysis step allowing removal of water soluble
molecules such as ammonia that accumulate in the presence of hepatic dysfunction
(8)
.
A
low protein diet and aperients to reduce colonic ammonia absorption are likely
to reduce the risk of further episodes of coma.
The patient and relatives should be educated about the possibility of
future episodes so that delays in diagnosis can be minimised if the patient
presents elsewhere.
Teaching
points
Hyperammonaemic
coma may occur in patients with previous urinary diversion surgery. Serum
ammonia should be measured in the presence of altered conscious level and
urinary diversion surgery.
Ammonia
is removed effectively by haemodialysis therapy because it is a small
non-protein bound molecule. Repeated haemodialysis sessions may be required
because of post-dialysis ’rebound’ of plasma ammonia concentration.
The
risk of hyperammonaemia following urinary diversion surgery is likely to be
reduced by a low protein diet and avoidance of constipation.
Acknowledgements
The authors would like to thank Dr Simon Dover and Dr Margaret McMillan for supervision of the patient’s care and for reviewing the manuscript and Dr Peter Galloway for measuring serum ammonia and clinical advice.
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