Departments of Anaesthesia and Medicine, University of Cape Town and Groote Schuur Hospital, South Africa*Corresponding author: Department of Anaesthesia, University of Cape Town Medical School, Anzio Road, Observatory 7925, Cape, South Africa
Keywords: complications, porphyria; biotransformation (drug); anaesthesia, evaluation, preoperative
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Introduction |
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The porphyrins play a critical role in biology, being involved in a wide range of reactions related to oxygen utilization, transport, storage or formation. The synthetic pathway involved in the production of the porphyrins is complex and is governed by a sequence of enzymes. A defect in any of these enzymes results in accumulation of the preceding intermediaries and produces one form or another of the diseases known as the porphyrias. This review briefly outlines porphyrin synthesis, the diseases that arise from errors in porphyrin metabolism and the anaesthetic implications of these disorders.
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Porphyrin metabolism |
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The biosynthesis of haem commences with formation of -aminolaevulinic acid (ALA) by the condensation and subsequent decarboxylation of two freely available moleculessuccinyl co-enzyme A (succinyl CoA) and the amino acid glycinein a step catalysed by the enzyme ALA synthetase. This process occurs in the mitochondria (where succinyl CoA is produced in the citric acid cycle); ALA synthetase appears to be the most important rate-limiting enzyme in porphyrin biosynthesis. The next step in porphyrin biosynthesis occurs outside the mitochondria where two molecules of ALA condense under the influence of the enzyme ALA dehydratase to form the monopyrrole subunit of the porphyrin ring, porphobilinogen (PBG). The enzyme PBG deaminase catalyses the condensation of four molecules of PBG to form hydroxymethylbilane, which is then converted into the first of the porphyrinogens, uroporphyrinogen, under the influence of uroporphyrinogen cosynthetase. The stepwise decarboxylation and conversion of uroporphyrinogen acetate groups to methyl substituents results in the formation of coproporphyrinogen which then re-enters the mitochondria where oxidation and chelation with ferrous iron result in the production of haem. These steps together with the relevant enzymes are illustrated in Fig. 2. The porphyrin biosynthetic pathway operates very efficiently and <2% of the porphyrin precursors are produced in excess of that required for haem synthesis. Consequently, the finding of increased concentrations of porphyrin intermediates in urine or stool indicates an abnormality of production, with a partial block somewhere in the enzymatic chain.
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Control of haem biosynthesis |
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ALA synthetase is readily inducible and can respond rapidly to increased haem requirements such as those resulting from the administration of drugs which require cytochrome P450 for their metabolism. Thus the availability and activity of the enzyme depend on the intracellular level of haem, and the demand for haem by metabolic processes. This fact is of great relevance in the development of the porphyrias, in which an increase in haem requirements in the face of a partial block in the synthetic pathway results in the overproduction of ALA synthetase, and consequently of the pathway intermediates before the block. The enzyme PBG deaminase also seems to have a regulatory role that is of relevance in some porphyric conditions. Under normal circumstances, an increase in production of ALA results in an increase in activity of PBG deaminase, thus enabling the synthetic pathway to continue efficiently. However, in acute forms of the disease, there appears to be a concomitant failure of PBG deaminase to respond appropriately, with a resultant accumulation of the early components of the metabolic pathway. Recent work has shown that coproporphyrinogen and protoporphyrinogen, both of which are produced in excess in variegate porphyria, can also inhibit PBG deaminase.34
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Classification of the porphyrias |
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The acute porphyrias |
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The enzyme defects in porphyria are deficiencies rather than absolute deficits. In most patients with clinically expressed porphyria, the level of enzyme reduction is generally of the order of 50%,26 suggesting that the defective allele produces essentially no enzyme activity. This may be why homozygotes are extremely rare, as complete failure to produce haem is probably incompatible with life. Increasingly, however, families are being identified in which mutations appear to encode proteins with some residual activity. Where such a family marries into another carrying a more typical mutation for the same defect, compound heterozygotes may result; such patients express low levels of enzyme and characteristically are phenotypically severely affected. Although there is no direct influence of gender on the pattern of inheritance, attacks occur more frequently in women and are most frequent in the third and fourth decades. Few cases have been reported before puberty, and attacks are rare after the menopause,29 although presentation has occurred between the ages of 7 and 75 yr.27 Acute attacks of porphyria are most commonly precipitated by events that decrease haem concentrations, thus increasing the activity of ALA synthetase and stimulating the production of porphyrinogens. Acute exacerbations may be precipitated by a number of factors, including physiological hormonal fluctuations (such as those occurring with menstruation), fasting, dehydration, stress and infection.14 Though pregnancy was thought to represent a particular risk in the porphyric patient, with acute attacks reportedly occurring in a high proportion of pregnant patients (2495%) with AIP,29 more recent experience suggests that the rate in pregnancy is lower. Frequent spontaneous abortion (612%) and hypertension may, however, complicate pregnancy in the patient with AIP and there is an increased incidence of low-birthweight infants. Nevertheless, enzyme-inducing drugs are by far the most important trigger factors, particularly in relation to anaesthesia.
Acute attacks are characterized by severe abdominal pain, autonomic instability, electrolyte disturbances and neuropsychiatric manifestations; they may range from a mild disturbance to fulminating attacks with a fatal outcome.17 Neuromuscular weakness, which may progress to quadriparesis and respiratory failure, is the most prominent and potentially lethal neurological manifestation, but sensory losses also occur. Central nervous system involvement with upper motor neuron lesions, cranial nerve palsies and involvement of the cerebellum and basal ganglia are less commonly seen. Permanent neurological lesions, especially parasympathetic dysfunction, can occur, particularly in AIP, although this is rarely seen unless the attacks have been multiple or of long duration. Though psychiatric disturbances were believed to occur in a high percentage of overt sufferers from the condition, the current belief is that these have been greatly exaggerated. Seizures may occur during an acute attack. Gastrointestinal symptoms are the most common and typically present with severe abdominal pain with vomiting and occasionally diarrhoea. Clinical examination of the abdomen is remarkably normal considering the severity of the symptoms,15 since there is no peritonism. Abdominal pain is thought to relate directly to the autonomic neuropathy, though there may be a contribution from abnormal bowel function with alternating areas of spastic and relaxed bowel. Ganglionic blockade may, therefore, be helpful in this condition,6 though it is seldom necessary, since the abdominal complaints commonly abate promptly with resolution of the attack. Dehydration and electrolyte abnormalities of Na+, K+ and Mg2+ may be severe and careful fluid and electrolyte management is essential. Cardiovascular instabilitywith tachycardia and arterial pressure changes of hypertension or, less commonly, hypotensionoccurs, particularly in AIP, and permanent hypertension may result.
Between attacks, complete remission is the norm, and many subjects with the genetic defect remain asymptomatic. This is particularly important when planning a drug regimen in patients potentially at risk, as patients with so-called silent (or latent) porphyria may have their first symptoms precipitated by injudicious administration of triggering agents. In all the acute porphyrias, acute attacks are characterized by markedly increased concentrations of ALA and PBG in the urine, though in PP the elevation is limited to ALA since the enzyme defect here lies before the step in which PBG is synthesized.
Drugs may trigger an acute attack of porphyria in many ways, most of which depend on an increased demand for haem production or a failure of haem inhibitory feedback as the final common pathway. Thus drugs may induce the transcription of ALA synthetase directly through mRNA or may interfere with the negative feedback control which haem exerts on ALA synthetase production. Drugs may interfere with the haem synthetic pathway, thus reducing the level of haem production, or they may increase the demand for haem by increasing utilization, for example through increased demand for oxidative processes mediated through the cytochromes. This multitude of potential pathways and the great variety of drug structures make it impossible to predict which agents are likely to be porphyrinogenic. The only properties of drugs which are clearly linked to porphyrinogenicity are lipid solubility11 and membrane fluidization.42 Some chemical groupings, such as the allyl groups which form the basis of the barbiturates, and certain steroid structures have also been incriminated in the induction of porphyria (steroids can enhance the induction of ALA synthetase). It is of interest that it is only the acute forms of the disease that are affected by enzyme induction, so this is the only form of the disease of pharmacogenetic importance. It is not clear why the manifestations of the non-acute forms of porphyria are not apparently affected by enzyme-inducing drugs. Even such potent inducers of ALA synthetase as the anticonvulsants do not exacerbate or precipitate porphyria cutanea tarda (PCT) or the erythropoietic porphyrias. The only apparent drug association with PCT is that of oestrogen-containing compounds. They may exacerbate the biochemical and skin manifestations of this condition, but acute attacks are never encountered in PCT. There are occasional reports of other agents being implicated in either the causation or exacerbation of the non-acute porphyrias, but Moore and colleagues concluded that the evidence for induction of these conditions by drugs other than oestrogens is weak.38. These conditions will, therefore, not be considered further. For more information about the non-acute porphyrias, see the review by Paslin.45 Notably, there is no excess excretion of ALA or PBG in these conditions, whereas these changes are the hallmarks of the acute porphyrias.
The pathogenesis of the acute porphyrias is unclear, although there are several possibilities. The excessive production of ALA is common to all of the acute forms and in all but the very rare plumboporphyria there is a defect in PBG deaminase, either in terms of an absolute reduction of enzyme activity, or in terms of a failure to increase its level in response to increased demand. Thus it is possible that ALA or PBG, or both, may be directly neurotoxic, although the severity of the symptoms does not correlate well with the increase in either of these substances. Nevertheless, the accumulation of these two compounds appears likely to have some effect on symptomatology. An alternative, but not exclusive, hypothesis is that the failure of haem production results in an acute haem deficiency within the nerve cell, and that this is the chief cause of the neuronal lesions, although the toxicity of ALA and PBG may still be relevant.38 It has also been suggested that haem deficiency results in a secondary reduction in the activity of haem-containing enzymes such as tryptophan oxygenase, with consequent disturbances in the production and metabolism of potential neurotransmitters such as serotonin.
Acute intermittent porphyria
The defective enzyme in this condition is porphobilinogen deaminase and the gene encoding this enzyme is located on chromosome 11. PBG deaminase deficiency can, in most cases, be detected in red cells between attacks. Of all the porphyrias, this one produces the most severe symptoms, and is the one in which an acute attack is most likely to be fatal. It has been reported that hypertension and impaired renal function are significantly more common in porphyric subjects than in their non-porphyric relatives, and that hypertensive complications and renal failure are the most frequent causes of death in patients with porphyria.9
Variegate porphyria
This condition is characterized by cutaneous photosensitivity in which bullous skin eruptions occur on exposure to sunlight as a result of the conversion of porphyrinogens to porphyrins. The characteristic skin lesion is one of excessive fragility, especially on sun-exposed surfaces such as the face and hands, where bullae and erosions with subsequent pigmented tissue paper scarring are frequently seen. The name of this condition derives from the fact that patients may present with the skin manifestations associated with the non-acute porphyrias, or the disorders characteristic of AIP or combinations of both. The enzyme defect is at the level of protoporphyrinogen oxidase but there is also a reduced amount of PBG deaminase. The gene encoding this enzyme is on chromosome 1. The incidence of VP in South Africa is the highest in the world: in some areas it may be as high as one in 250 of the white population.12 This has been shown to result from the introduction of a single point-mutation by a Dutch settler in 1688.35
Hereditary coproporphyria
This condition is far less common than VP and AIP. Acute attacks appear to be considerably less severe, and the prognosis better. The defective enzyme is coproporphyrinogen oxidase, encoded by a gene on chromosome 9. As in VP, cutaneous photosensitivity is characteristic, though it tends to be less severe in the interval between acute attacks than it is in VP.
Plumboporphyria
This, the rarest of the acute porphyrias, results from a deficiency of ALA dehydratase, which is encoded by a gene on chromosome 9. It is associated with an excess of urinary ALA analogous to that found in lead poisoning (hence the name), although lead concentrations in the blood are normal. Unlike the other acute porphyrias, the mutation is recessive, and the disease presents early in life, with all clinically manifest cases being homozygotes.19 No references to anaesthesia for patients with this condition have been published.
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Implications for anaesthesia |
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Identification of susceptible individuals |
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Identification of drugs |
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In view of the difficulties clinicians experience in interpreting such terms as possibly safe and probably unsafe in drug lists, the Porphyria Drug Safety Database held at the University of Cape Town has been reviewed and modified to reflect the terms listed in Table 3, which give a clearer indication of the relative desirability of drugs. Those drugs most applicable to anaesthesia are listed in Table 4. The information presented in this table was obtained by examining data from the literature (itself based on clinical experience as well as animal and in vitro experiments), from personal experience and by the examination of drugs for structure, structural similarity and routes of metabolism. As such it represents both compromise and intuition unsubstantiated by hard data, and the recommendations cannot be guaranteed to prove valid under all circumstances. The list should serve as a guide only, and the authors cannot accept responsibility for errors or for any adverse experience. More information on specific agents may be obtained from the authors.
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Anaesthetic management |
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If an acute crisis is suspected, particular attention must be paid to muscle strength and cranial nerve function, as symptoms related to these areas may predict impending respiratory failure or an increased risk of aspiration. Cardiovascular examination may reveal hypertension and tachycardia; these should be treated before anaesthesia. Respiratory muscle function may be compromised, and respiratory function tests may be indicated. In an acute crisis, postoperative ventilation may be required. During an acute exacerbation, the possibility of non-surgical abdominal pathology must always be suspected, with a high index of suspicion in a patient in whom the severity of symptoms is not matched by clinical findings. Preoperative preparation in a patient with an acute porphyric crisis must include the careful assessment of fluid balance and electrolyte status.
Premedication
Most (but not all) benzodiazepines commonly used for premedication are considered safe. The phenothiazines may have particular advantages. Good anxiolysis has been recommended as advantageous.1 Where antacid administration is considered appropriate, sodium citrate may be given and ranitidine may be considered. Cimetidine has been recommended in the treatment of acute porphyric crises, since it may decrease haem consumption and inhibit ALA synthetase activity.27 However, although it may be used safely as an H2 receptor antagonist, it does not appear to be effective prophylactic therapy.27 Preoperative starvation should be minimized; if a prolonged fast is unavoidable, a dextrosesaline infusion should be given during the preoperative period, since calorie restriction has been linked with the precipitation of acute attacks. In view of the frequency with which hyponatraemia is encountered in acute attacks, intravenous fluids containing dextrose alone should be avoided.
Regional anaesthesia
There is no absolute contraindication to the use of regional anaesthesia in the porphyric patient. However, careful examination and evaluation of the neurological status of the patient before the performance of a regional block is essential. Cardiovascular stability may be compromised by hypovolaemia and autonomic neuropathy.
Theoretically, lidocaine, which has been shown to be potentially porphyrinogenic in both of the commonly used animal models, should be considered unsafe. However, wide experience with the agent has not shown significant problems either when used as a local anaesthetic or when used intravenously for the control of arrhythmias, although experience with the latter usage is limited. On the basis that a worsening of the neuropathy might be ascribed to epidural anaesthesia, fear of litigation has been raised as an argument against the use of regional blockade.26 However, as there is no evidence that any local anaesthetics have ever induced an acute attack or neurological pathology in porphyric subjects, there seems no good reason to avoid their use. This view is supported by a report of two instances of the use of regional anaesthesia in AIP during pregnancy in both of which bupivacaine (one epidural and one spinal administration) was used without complication.32 The authors concluded that there was no evidence that general anaesthesia was safer for the pregnant porphyric patient than regional anaesthesia. In theory, procaine is the best agent to use, but in practice bupivacaine appears to be safe, and the intrathecal route, in which a minimum of agent is injected, seems ideal. The epidural use of procaine and fentanyl in a pregnant porphyric patient has been reported.28 Böhrer and Schmidt4 reported two cases managed with local anaesthesia and concluded that regional or local anaesthesia with bupivacaine, prilocaine, tetracaine or procaine may be the technique of choice for porphyric patients whenever the technique was applicable. However, problems with haemodynamic instability, mental confusion and associated neuropathy probably preclude the use of regional anaesthesia in the presence of an acute porphyric crisis,1 27 although there are no studies specific to this issue.
General anaesthesia
The total dose of drug administered and the length of time for which the patient is exposed to the drug may influence the probability of triggering a porphyric crisis. The current availability of very short-acting anaesthetic agents almost certainly contributes to the increased safety of most modern anaesthetic techniques, although there are still some areas of controversy.
Induction. The barbiturates are the archetypal inducers of ALA synthetase, and all barbiturates, including thiopental, must be considered unsafe. Although there are numerous reports of the safe use of thiopental in porphyric patients in the quiescent phase,53 seven out of 10 patients in acute porphyric crisis had their symptoms worsened following induction of anaesthesia with thiopental.40 Thus, although thiopental will not always precipitate a crisis, all barbiturates must be considered contraindicated in porphyric patients. Etomidate is potentially porphyrinogenic in animal models23 and at least one crisis has followed its use in human subjects, although its safe use has also been reported;18 on balance, etomidate should probably be considered unsafe. Ketamine is probably safe; it has been used safely in quiescent AIP;2 47 52 its safe use during a crisis in HCP has been reported,7 and most animal and cell culture models suggest that it is non-inducing. However, an increase in ALA, PBG and other porphyrins after ketamine has been reported in a patient in the latent phase of AIP, and it would seem wise to reserve ketamine for use where haemodynamic or other considerations make it the drug of choice. The use of propofol in porphyria is also contentious to some degree. Animal data are conflicting; there is no evidence of porphyrinogenicity in the DDC-primed rat, but some evidence of induction of ALA synthetase in the chick embryo.13 There are many case reports of patients with AIP8 10 25 29 31 37 46 50 58 and HCP48 and a prospective study of patients with VP36 who received propofol safely. Although there are two reports of elevated porphyrins following propofol anaesthesia in patients with VP59 and AIP,16 continuous infusions of propofol were used in both cases and total doses of 900 or 1300 mg were administered; neither patient had any porphyric symptoms following the use of propofol. On balance, therefore, it appears that propofol can safely be used for induction of anaesthesia, although a question mark must remain against its use as a continuous infusion.
Inhalational agents. Nitrous oxide is well established as safe and cyclopropane and ether are also thought to be without risk. Halothane has been used in many cases of porphyria and is generally regarded as safe. There are two cases of a possible hazard attributed to halothane supported by some experimental evidence.22 However, in view of other experimental data which do not support this view, together with extensive clinical experience of its use, halothane may be listed as safe.22 This is particularly important as the status of the other two main potent inhalational agents, enflurane and isoflurane, is less certain. Safe use of isoflurane has been reported5 6 2931 and there appear to be no reports of adverse effects. Isoflurane should probably, therefore, be classified as safe, although further information needs to be obtained. Enflurane has been shown to induce porphyrin synthesis in animal models5 43 but has been used safely in patients. There are few reports of its use, but there seems no absolute contraindication to enflurane in porphyric patients. There are no published data relating to sevoflurane or desflurane, although the short duration of action of both agents, and the minimal metabolism of the latter, make them likely to be safe. On balance, halothane would appear to be the current agent of choice, and isoflurane may be a satisfactory alternative; none of the other newer halogenated hydrocarbons are as yet absolutely contraindicated, though caution should be exercised in view of the very limited experience with their use in porphyric patients.
Neuromuscular blocking drugs. Succinylcholine has been used for many years and has been proven to be safe, as has tubocurarine. Though both pancuronium and alcuronium have been classified as unsafe by some authors, they have been widely used by many anaesthetists without harm. Atracurium6 29 30 and vecuronium31 have been used safely in small numbers of patients despite some experimental evidence for porphyrinogenicity. There would appear to be little to choose between these various agents; by analogy, mivacurium and rocuronium too are unlikely to prove dangerous, though there are no published data on their safety. Caution should, however, be exercised, particularly where extended use is intended, for example in the patient in the intensive care unit undergoing prolonged ventilation. As with propofol, prolonged use may not be safe, whereas a single dose may be.
Analgesic agents. Morphine and its analogues (including codeine) are of proven safety, and fentanyl has been shown to be safe both in chick embryo culture models and in clinical use. Alfentanil has also been used frequently with no reported complications. More recently, fentanyl55 and sufentanil54 have been used as a major component, in combination with isoflurane and atracurium, in open heart surgery without problems.6 These cardiac surgical reports also refer to the safe use of heparin. Pethidine (meperidine) has a proven track record of safety despite a single case report implicating it in a porphyric attack.14 Pentazocine and tilidine have been listed by several authors as unsafe, though the reasons for this are unclear. There is evidence both for44 and against13 the porphyrinogenicity of pentazocine in experimental systems. Of the non-opiate analgesics, aspirin, acetaminophen, indomethacin and naproxen have proven safe. Disler and Moore14 recommend the avoidance of the pyrazalone derivatives (such as phenylbutazone), the anthranic acid derivatives (such as ibuprofen and fenoprofen) and diclofenac. There is no information regarding ketorolac.
Cardiopulmonary bypass is a specific problem, as the additional stress imposed by hypothermia, the haemolysis induced by the bypass pump, blood loss and the large number of pharmacological agents that need to be administered may all worsen the risk of development of a porphyric crisis. However, there are several reports of the safe performance of cardiac surgery in porphyric patients provided that appropriate drug regimens are selected.49 51 54 55 Blood loss, with its consequent increase in haem demand by the bone marrow, does not appear to stress the haem synthetic pathway sufficiently to provoke a porphyric crisis.20
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Guidelines for selecting drugs for anaesthesia in patients with porphyria |
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(i) There is evidence that single exposures to potent inducers, such as thiopental, are often tolerated, but that exposure in patients whose porphyria is already induced is dangerous.40 It seems likely that the risk with modern, short-acting anaesthetic agents is low, possibly because their rapid elimination means that exposure time is not long enough for significant enzyme induction to occur. Repeated or prolonged exposure may, however, be dangerous, as may be the case with propofol described above.
(ii) There is reason to believe that exposure to multiple potential inducing agents may be far more dangerous than exposure to any one drug.
(iii) Some of the drugs traditionally listed as unsafe on the basis of animal or cell culture experiments may not, in practice, be unsafe.
(iv) Case reports reporting adverse outcomes are frequently unreliable. They may be written by clinicians inexperienced in the interpretation of porphyrin biochemical data; sometimes this amounts to blatant ignorance, as when drug outcomes are reported in patients with PCT, which is not an acute porphyria.
This has led to the more recent, lenient approach to recommendations for drug administration reflected in Table 4 and in the paragraphs above. However, a more relaxed approach is under no circumstances to be confused with a careless or unthinking approach. Every patient must be assessed individually. In particular, patients with evidence of more active porphyria or a history of acute attacks, particularly of AIP, and prolonged administration of drugs not known unequivocally to be safe, or their sequential or concomitant use, provide fertile ground for the precipitation of an attack.
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Inadvertent use of porphyrinogenic drugs |
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Should an acute attack occur, the first step in management is to ensure that any possibly precipitating factors are withdrawn. Adequate hydration and carbohydrate intake must be ensured in the face of the nausea and vomiting which accompanies the acute attack; use of a nasogastric tube may be necessary. Pain often requires opiates in high and frequent doses. Sedation with phenothiazines may assist by encouraging sleep, which has been reported to diminish the pain, but is usually unnecessary when sufficient doses of opiate have been given. Nausea and vomiting will respond to the phenothiazines, and ondansetron may be useful if extrapyramidal side-effects occur, although its use in this setting has not been described. Beta-adrenergic blockers may be valuable in controlling tachycardia and hypertension, and may also decrease the activity of ALA synthetase. Fluid balance and electrolyte disturbances must be managed aggressively. Magnesium sulphate infusions may be useful in the management of crises associated with magnesium deficiency.56 Should convulsions occur, the traditional anticonvulsants are, of course, largely contra-indicated, but diazepam and clonazepam may be used. Haematin is the only specific form of therapy; it is thought that it supplements the intracellular free haem pool, thus repressing ALA synthetase. This agent, together with advice on its use, is usually available from expert centres specializing in porphyria. However, it is unstable and can cause renal failure, thrombophlebitis and dose-related coagulopathy.1 3 39 Haem arginate is more stable and does not have the adverse effects attributed to haematin.41 It may be preferable to haematin.57 Somatostatin decreases the rate of formation of ALA synthetase and, together with plasmapheresis, has been used successfully to reduce pain and produce complete remission of symptoms in seven porphyric patients with acute exacerbations.33
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Conclusions |
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The simplest course for the practising anaesthetist to adopt is not to attempt to remember a large range of drugs that are potentially hazardous, but rather to develop a simple, safe technique based on agents that have minimal risk of triggering a porphyric crisis. On the basis of the literature reviewed in this article, it would appear that propofol is now the induction agent of choice, although ketamine may be used if required. Most muscle relaxants appear to be reasonably safe, and all of the inhalational agents, with the possible exception of enflurane, can probably be used. Analgesia can be provided with any of the opiates currently in use, though tilidine and pentazocine should be avoided and care should be taken in choosing a non-steroidal anti-inflammatory agent. Regional anaesthesia, with any of the currently available agents, is not contraindicated and may be of benefit where appropriate. There is thus a more than adequate range of pharmacological agents available for use in the porphyric patient. The choice of agent may be based more on the patients anaesthetic and surgical requirements, rather than governed by the specific requirements imposed by porphyria.
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References |
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