TREATMENT OF THE ACUTE ATTACK
of the acute attack should be made by measuring
quantitative PBG before starting specific
treatment for porphyria (eg with human hemin)
about diagnosis). For patients who
have previously had an unequivocally diagnosed
attack of acute porphyria, it may be necessary
to initiate specific treatment before the
results of the laboratory investigation are
| Withdraw any drugs
or other potential provoking agents.
I. SUPPORTIVE TREATMENT
Start appropriate supportive treatments using
drugs that are safe in acute porphyria. Recommended
drugs and procedures are listed below.
or other procedure
about pain management)
(oral, sublingual, intravenous or subcutaneous)
| Sedation, decrease
| Analgesic requirement
(further information on anti-convulsants)
| Correct any hyponatraemia
| Propranolol 1
| Muscle weakness/paralysis
| Monitor progress
| Bulk forming laxatives
Senna Prostigmin (neostigmine bromide)
low doses may provoke severe hypotension
Opiates are the most effective analgesics for
use in an acute attack. Since acute attacks are
usually short lived and infrequent, opiates may
be used in high doses without fear of addiction.
Chlorpromazine or promazine may help to decrease
the requirement for analgesics. In some patients,
residual neuropathic pain continues once the acute
attack has settled. It is important to recognise
that this pain differs from that of the acute
attack itself and, wherever possible, to avoid
using addictive analgesics for its management.
Careful management of fluid balance, avoiding
large volumes of hypotonic dextrose, is required
to minimise the risk of severe hyponatraemia which
may provoke convulsions. Hyponatraemia should
be corrected slowly; patients with acute attacks
seem particularly prone to cerebral oedema and
osmotic demyelination. Restriction of water intake
to around 500 mL per day may be sufficient alone
but, if symptoms necessitate saline infusion,
the rate of correction should not exceed 8 mmol/L
in any 24 hour period.
Since impaired nutrition may aggravate acute
porphyria, it is important to ensure that adequate
calories are given. They are preferably given
as carbohydrate-rich food supplements orally or,
if necessary, via a nasogastric tube. When vomiting
prevents enteral administration, carbohydrate
may be provided as normal saline with 5% dextrose,
two litres of which provide 100 g of glucose per
day. Avoid infusing large volumes of hypotonic
dextrose as this aggravates hyponatraemia. As
soon as patients are able to take food orally,
they should be transferred to a diet in which
carbohydrate provides 55-60% of the energy needed
to maintain their normal weight.
Cardiovascular complications such as hypertension
and tachycardia are rarely sufficiently severe
to require therapy in their own right. Very occasionally,
the acute attack is accompanied by a severe adrenergic
crisis with dangerous hypertension, encephalopathy,
seizures and ischaemic changes on CT brain scanning.
Intravenous infusion of magnesium sulphate may
be effective in controlling the adrenergic symptoms;
human hemin must be administered to abort the
The onset of a motor neuropathy is often marked
by severe pain and stiffness in the thighs and
back followed by loss of tendon reflexes and motor
paralysis. When vital capacity becomes severely
reduced by paralysis of the intercostal muscles,
artificial ventilation is necessary and may have
to be continued for several months until the expected
eventual recovery occurs.
II. SPECIFIC TREATMENT
Specific treatment should be started as soon
as the diagnosis is established unless the attack
is mild and clearly resolving. Two treatments
are available: intravenous heme and carbohydrate
loading. Intravenous heme is the more effective
and should be used unless heme preparations are
unavailable. Neither will reverse an established
peripheral neuropathy, though heme may prevent
its onset and may halt further progression of
neuropathy if given sufficiently early.
(human hemin, Orphan
Europe) is a concentrated heme solution
(250 mg heme per ampoule) in which heme
is stabilised as a complex with arginine
(267 mg) suspended in a mixture of ethanol
(1g) and propyleneglycol (4g) made up to
10 ml with water. The recommended dose
is 3mg/kg body weight up to 250mg given
on each of four consecutive days. It is
often convenient to use a dose of 250mg
for adults irrespective of their weight.
In the summary of the product characteristics,
it is recommended that the concentrated
heme arginate solution should be mixed with
100mL physiological saline in a glass container
immediately before infusion into a large
peripheral vein or through a central venous
line over 15-20 mins. Once diluted, the
heme becomes unstable and may aggregate
if there is undue delay. After infusion,
the vein should be washed with saline for
10-15 min. Repetitive use of Normosang®
can lead to vein toxicity in the form of
disappearance of the superficial venous
system and the consequent need for a central
catheter. With time, these catheters may
become obstructed by heme deposits. Current
experience suggests that diluting the human
hemin in 100ml of human albumin (4-20% depending
on country availability) instead of saline
solution delays or suppresses these problems.
For more details (more
about porphyria specialist centres).
Heme as a lyophilized
powder (Panhematin; Abbot Laboratories)
is available in the United States where
human hemin (Normosang®) does
not have FDA approval.
TREATMENT WITH HUMAN HEMIN (Normosang®)
Normosang® should be given as soon
after the onset of the attack as practicable.
In a mild attack, it may be acceptable to allow
24 hours for spontaneous settling of the attack.
Otherwise, it should be given promptly, if possible
within 24 hours of admission, to any patient with
severe symptoms (severe pain, vomiting), or who
shows complications such as seizures, hyponatraemia,
or incipient neuropathy, and also to any patient
with a history of a previous attack complicated
by neuropathy. If delay is unavoidable, carbohydrate
loading may be carried out as described below.
Measurement of urinary ALA or PBG excretion is
useful to document the metabolic response to human
Most patients improve within 5 days but, if necessary,
the course may be repeated after a day or two
but the effectiveness of prolonged treatment has
not been evaluated.
Few side effects have been reported for the short-term
use of Normosang®. The coagulopathies reported
with other heme preparations do not occur with
Normosang®. Though thrombophlebitis at
peripheral vein infusion sites has been reported
in less than 1% of cases, our own experience is
that it is much commoner. The most frequently
observed phenomenon after several courses of Normosang®
is the disappearance of the superficial venous
system and the need for an indwelling venous access
(Portacath®) Administration in 4-20% human serum
albumin (see above) greatly reduces the incidence
of phlebitis. Hypersensitivity reactions are
very rare. Attacks during pregnancy have been
treated without any apparent adverse effects on
mother or child. Each 250mg dose of heme contains
22.7mg of iron; about one tenth of the iron in
one unit of blood. Iron overload is therefore
a potential problem only in patients treated on
Two litres of normal saline with 10-20% glucose
given in divided doses of 500 ml over 24 hours
through a central venous catheter. Carbohydrate
loading has now been replaced by heme preparations
as the treatment of choice for an acute attack
III. REPEATED ATTACKS
Less than 10% of patients have frequently repeated
acute attacks. Advice on their management should
be sort from a specialist centre. Special measures
include gonadorelin analogues for repeated premenstrual
attacks and long-term treatment with human hemin.
1. Anderson KE, Spitz IM, Bardin CW,
A gonadotropin releasing hormone analogue prevents
cyclical attacks of porphyria.
Arch Intern Med 1990; 150: 1469-74.
2. Bonkovsky HL, Tschudy DP, Collins
A et al.
Repression of the overproduction of porphyrin
precursors in acute intermittent porphyria by
intravenous infusions of hematin. Proc Natl
Acad Sci 1971; 68: 2725-9.
3. Bonkovsky HL.
Advances in understanding and treating 'The little
imitator', acute porphyria.
Gastroenterology 1993; 105: 590-94.
4. Brodie MJ, Moore MR, Thompson GG,
The treatment of acute intermittent porphyria
Clin Sci Mol Med 1977; 53: 365-71.
5. Dover SB, Moore MR, Fitzsimmons EJ,
Graham A, McColl KEL.
Tin protoporphyrin prolongs the biochemical remission
produced by heme arginate in acute hepatic porphyria.
Gastroenterology 1993; 105: 500-506.
6. Elder GH, Hift RJ.
Treatment of acute porphyria.
Hospital Medicine 2001; 62: 422-25.
7. Gorchein A.
Drug treatment in acute porphyria.
Br J Clin Pharmacol 1997; 44: 427-34.
8. Herrick AL, McColl KEL, Moore MR,
Cook A, Goldberg A.
Controlled trial of heme arginate in acute hepatic
Lancet 1989; i: 1295-97.
9. Kalman DR, Bonkovsky HL.
Management of acute attacks in the porphyrias.
Clin Dermatol 1998; 16: 299-306.
10. Mustajoki P, Nordmann Y.
Early administration of heme arginate for acute
Arch Intern Med 1993; 153: 2004-08.
11. Robert TL, Varella L, Meguid MM.
Nutrition management of acute intermittent porphyria.
Nutrition 1994; 10: 551-55.
12. Tenhunen R, Mustajoki P. Acute porphyria:
treatment with heme.
Seminars in Liver Disease 1998; 18:
to PubMed >>