MANAGEMENT OF THE ACUTE ATTACK

Specific therapies are few: these include the use of high carbohydrate intake and haematin infusion. Initially, steps should be taken to ensure an adequate carbohydrate intake. Most patients suffer from nausea and vomiting during an attack and their poor carbohydrate intake aggravates the disease process. This cycle must be broken. In mild attacks, this is achieved by ensuring an adequate oral intake of Glucose Polymer drinks, such as Caloreen (Roussel) or Hycal (Beecham Products). In patients experiencing more severe attacks, the constant slow infusion of Carbohydrate solution via a fine bore Teflon nasogastric tube, is helpful. If the symptoms are not controlled, an infusion of Haem Arginate should be considered.(See below). This treatment is still on trial and may be obtained from the appropriate drug company on a named patient basis.
 
 

Symptomatic Therapy Pain

This is a feature of most attacks. When mild, it may be adequately controlled with aspirin, paracetamol or dihydrocodeine. For more severe pain, pethidine (meperidine), morphine or diamorphine may be required. Buprenorphine, which may be administered either sublingually or intramuscularly, is also useful. More constant pain relief may be achieved by the continuous intravenous infusion of analgesics. There is a danger of addiction in patients experiencing frequent attacks, who require large amounts of narcotic analgesics, and every attempt should be made to withdraw all narcotic drugs between attacks.

In a few unfortunate patients, the pain is refractory to even very large doses of narcotic analgesics, and signs of respiratory and cardiovascular system depression appear before pain relief is obtained. Many of our patients report that the only time the pain goes away is when they are asleep. This observation may be used to advantage by encouraging sleep for several hours by combining chlorpromazine or promazine with the analgesics and leaving the patient undisturbed in a darkened room.

Some patients continue to complain of chronic abdominal pain, unaccompanied by any other symptoms between attacks. This can be very difficult to manage, and the risk of narcotic addiction in these patients is high. Although, sometimes, a psychological overlay may be a factor - in others, the pain is clearly genuine and presumably a manifestation of residual neurological damage.

Nausea, Vomiting and Constipation:

These are frequent symptoms and may be controlled with chlorpromazine, promazine or prochlorperazine. As the narcotic analgesics used in controlling the pain often aggravate the nausea and vomiting, it is usually helpful to administer antiemetics with or shortly before the analgesics. Besides their antiemetic effects, chlorpromazine and promazine control the agitation and other psychiatric manifestations of the attack. In our experience, some porphyria patients develop extrapyramidal side-effects with phenothiazines, necessitating substitution with cyclizine hydrochloride. Constipation, where it occurs, may be severe - to the point of obstipation - and Neostigmine is beneficial in these circumstances.

Tachycardia and Hypertension:

These are present in most attacks. They are thought to be the result of sympathetic overactivity and should be controlled with propranolol. The dose can be titrated against its effect on the Cardiovascular System. Frequently very large doses are required. The pulse and blood pressure should be closely monitored, as they tend to be labile and hypertensive encephalopathy may develop. Postural hypotension, leading to syncope, may occur when a patient sits upright, even when the patient has been hypertensive in the supine position. When postural hypotension does occur, the supine blood pressure should still be adequately controlled with propranolol, taking care when moving the patient. Paroxysmal cardiac arrhythmias, sometimes leading to collapse, may also occur. These may be precipitated by the patient suddenly sitting upright. Whenever there is evidence of cardiovascular instability, continual ECG monitoring should be performed and full resuscitative facilities kept at hand.

Convulsions:

Convulsions are not infrequent at the peak of an attack. Their onset may be a sign of hyponatraemia, due to inappropriate antidiuretic hormone secretion, and plasma osmolality, and electrolyte values should be checked. If hyponatraemia is the underlying cause, it should be corrected by restricting fluid intake to not more than 700 ml. The onset of convulsions may also be a sign of hypertensive encephalopathy, and the blood pressure should be checked. Convulsions, occurring during the attack, usually disappear as the attack resolves and, therefore, therapy should be aimed at treating the underlying disease process.

Some patients continue to experience convulsions while in remission. This presents a therapeutic dilemma. Phenobarbitone, primidone, phenytoin and carbamazepine all increase cellular haem utilisation by inducing the synthesis of hepatic monoxygenases, and are contraindicated. The benzodiazepines and sodium valproate are not inducers of the monoxygenases and, although they are porphyrinogenic in experimental models of porphyria, there is limited evidence that they are porphyrinogenic in man. Status epilepticus, in our own experience, has been treated successfully with intravenous diazepam. Seizure prophylaxis can be undertaken as a calculated risk with clonazepam or sodium valproate if this is essential, although sporadic clinical reports of porphyr- inogenicity do exist. Sodium bromide and magnesium sulphate are safe, but generally outmoded anticonvulsants.

Neuropathy:

All patients should be examined for evidence of developing peripheral neuropathy. This may progress rapidly, leading to quadriplegia and bulbar and ventilatory paralysis. The latter is heralded by weakening of the voice. When signs of peripheral neuropathy are present, the expiratory peak flow-rate should be monitored. If there is any reduction in this rate, the blood gases should be checked, and the patient nursed in an Intensive Care Unit with facilities for assisted ventilation. Even in patients in whom there is widespread paralysis requiring assisted ventilation for many months, good functional recovery can still be expected. Attention should be given to splinting of the joints and appropriate physiotherapy in the paralysed patient.

Fluid and Electrolyte Balance:

Various disturbances of fluid and electrolyte balance are seen during the acute attack. Dehydration may occur, owing to persistent vomiting. Hyponatraemia, secondary to inappropriate antidiuretic hormone secretion, may also occur, sometimes first becoming apparent after commencing intravenous fluids. The hyponatraemia can usually be controlled by restricting fluid intake. To maintain adequate carbohydrate intake while restricting fluid intake, it may be necessary to use higher concentrations of glucose, administered via a central venous line.