Anaesthesia for patients with idiopathic environmental intolerance and chronic fatigue syndrome
Royal North Shore Hospital of Sydney, St Leonards, NSW 2065, Australia
* Corresponding author. E-mail: mfisher{at}med.usyd.edu.au
Accepted for publication July 21, 2008.
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Abstract |
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Background: Idiopathic environmental intolerance syndrome (IEI), formerly known as multiple chemical sensitivity syndrome (MCSS), and chronic fatigue syndrome (CFS) are controversial diseases and there is little information in the literature regarding the appropriate conduct of anaesthesia in such patients.
Methods: We studied 27 patients referred to our anaesthetic allergy clinic with IEI and CFS and performed literature and web searches on anaesthesia in these disorders.
Results: The patients had a significant incidence of adverse events related to anaesthesia which were not allergic in nature. The adverse effects usually occurred postoperatively and were self limiting. Patients with IEI and CFS are not at risk of anaphylaxis and there is no scientific evidence that any drug or technique is excessively hazardous. Neither our patients nor the review of the scientific literature supported available web-based recommendations for the anaesthetic management of patients with IEL and CFS.
Conclusions: We suggest that the anaesthetist may be best to use the technique they would use if the patient did not have CFS or IEI but avoid drugs to which there is a history of adverse response. Anaesthesia is likely to be associated with adverse effects in these patients but the effects are not likely to be severe. A series of recommendations for the safe and harmonious conduct of anaesthesia in patients with CFS and IEI are provided.
Keywords: allergy; anaesthesia, adverse effects; chronic fatigue syndrome; idiopathic environmental intolerance; multiple chemical sensitivities
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Introduction |
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Idiopathic environmental intolerance (IEI) syndrome and chronic fatigue syndrome (CFS) are complex and controversial disorders producing diverse symptoms in response to diverse stimuli. There is a lack of valid studies establishing the pathogenesis or origin of these syndromes. IEI syndrome has also been known as multiple chemical sensitivity syndrome (MCSS), environmental illness, universal allergy, twentieth-century disease, chemical hypersensitivity syndrome, total allergy syndrome, cerebral allergy,1 and sick building syndrome.2–5 CFS has a similar spectrum of symptoms to fibromyalgia and myalgic encephalomyelitis.6 There is overlap between the conditions7 and the reported incidence of doctor-diagnosed IEI in one study of 4064 patients was 6.3%.6 The prevalence of CFS has been estimated to be between 75 and 267 per 100 000 in the community.8 There is an important psychological component to both disorders, with both groups suffering a higher incidence of psychiatric disorders, particularly anxiety and depression,2 and symptoms with no medical explanation than in control groups.2 3 A systematic review of provocation studies has suggested that reactions to chemical challenges in IEI might not be related to the chemical itself but their expectations and prior beliefs.4 Further, the disorders are pervaded by uncertainty and have been described as ‘contested illnesses’ leading to conflict between sufferers and providers.3 4 Both disorders affect females twice as commonly as males, with a peak between early 20s and mid-40s.9 Adverse reactions to drugs, foods, vapours, and environmental chemicals are a feature of both disorders, and the clinical manifestations are usually symptoms rather than signs.1 2 In spite of these conditions being relatively common and carrying a perceived risk of adverse drug reactions, there is little information in the medical literature regarding anaesthesia in these conditions. For this reason, in these conditions, the internet may become a major source of information.5
In this article, we describe the experience of an anaesthetic allergy clinic with patients with IEI and CFS and review the literature and information available on the internet to assess the risks of anaesthesia in these patients.
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Methods |
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Over a 20 yr period, there were 27 patients referred to an anaesthetic allergy clinic, because of perceived risk of, or a history of, adverse reactions after anaesthesia and a history of IEI, CFS, or both. Twenty-five of these patients were investigated by intradermal testing for drugs used in general anaesthesia, progressive challenge for local anaesthetic drugs using methods previously described, or both.10 11 Where patients had adverse events allegedly related to anaesthesia, we endeavoured to obtain the anaesthetic records and tested for the drugs used and all the available neuromuscular blockers. Patients who were referred before anaesthesia were tested for drugs the anaesthetist wished to use. All patients were given letters describing their anaesthetic experience with recommendations regarding future anaesthesia. We endeavoured to obtain the records of all anaesthesia before and subsequent to the clinic consultation.
A literature search was performed using Ovid and PubMed using the terms chronic fatigue syndrome, idiopathic environmental intolerance, fibromyalgia, myalgic encephalitis, myalgic encephalomyelitis, MCSS, sick building syndrome and anaphylaxis, anaesthesia, orthostatic hypotension, and skin testing. The Ovid search was from 1950 to June 2007.
Papers considered likely to be relevant to anaesthesia were retrieved and reviewed.
To search the internet, we used Google and searched ‘chronic fatigue syndrome and anaesthesia’ and ‘multiple chemical sensitivity syndrome and anaesthesia’. The first 20 sites for each group were examined in detail.
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Results |
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Twenty-seven patients (24 females and three males) were referred to an anaesthetic allergy clinic with a history of IEI (12), CFS (nine), or both (six). Four patients had never had an anaesthetic problem and were referred for direction for future anaesthesia and the remainder were referred because of a history of problems related to local anaesthesia (seven), general anaesthesia (12), or both (eight).
A number of patients had particular requests relating to the conduct of anaesthesia, particularly the avoidance of volatile agents, epinephrine, or specific drugs. The perioperative records were obtained in 11 cases and analysed for evidence of problems. Intraoperative hypotension was described in two patients and postoperative hypotension in three. All responded to fluids and none received vasoactive drugs. Three patients took over an hour to awaken. One patient developed diarrhoea, hypoglycaemia, and hypertension in recovery. One of the patients with intraoperative hypotension described a cardiac arrest that had been covered up. There was a well-documented anaesthetic record showing an uneventful anaesthetic and both surgeon and anaesthetist recalled the patient and denied any adverse event. The other patients all had medically unexplained symptoms that occurred after hospital discharge. These symptoms included panic attacks (two), uncontrollable shaking (two), protracted nausea (four), limb pains (two), and tiredness and weakness (five).
A further patient had untoward reactions after regional block (two episodes) and general anaesthesia (four episodes) and both she and her referring doctor believed her CFS had been caused by the anaesthesia. Her initial symptoms were blurred vision, sweating, insomnia, lethargy, and hair loss. After an epidural, she reported that one leg had shrunk. The records of four of these anaesthetics showed no intraoperative problems. It was not possible to identify any particular drug that appeared to be associated with the problems.
The patients who reacted after local anaesthesia had vasovagal reactions (three immediate and two delayed), swelling (six) or medically unexplained symptoms including hallucinations (two), or difficulty in remaining awake (three).
Skin testing
Intradermal testing was undertaken in all patients referred to the anaesthetic allergy clinic with the exception of one patient who refused skin testing after the risks were explained. Testing was performed for general anaesthetic drugs (six) and progressive challenge for local anaesthetic drugs (without additives) (four) or both (16).
Two patients had vasovagal reactions to saline controls before progressive challenge and one patient became emotional while driving home and had to stop the car. She identified the reaction as psychological.
A further patient, with multiple chemical sensitivities and cardioneurogenic syndrome developed non-itchy wheals on the opposite arm during cutaneous testing. When tested subsequently with drugs one at a time at an interval of 1 day, the reaction recurred with propofol only. All other skin tests were negative and progressive challenge tests were negative.
We have stopped skin testing these patients as the results bore no relationship to outcomes.
Subsequent anaesthesia
We have records of 38 general anaesthetics, eight local anaesthetics, and three anaesthetics where both local and general anaesthetic drugs were used. The subsequent anaesthetics included a number of drugs specified as potentially problematic in IES and CFS patients on websites, including thiopental, morphine, all the volatile anaesthetics, atracurium infusions, lidocaine, and local anaesthetics containing vasoconstrictors. Only one patient of these 27 experienced difficulties after referral and investigation. This patient suffered both IEI and CFS and was wheelchair and house bound by her disease. She had problems at home after three anaesthetics, including hemiplegia, hallucinations, memory loss, seizures, narcolepsy, red lines on the abdomen, and low arterial pressure which she and her partner managed without medical referral. She has subsequently had major surgery which required a prolonged stay in hospital and experienced only nausea.
Literature review
The literature review found six papers with Ovid and 117 with PubMed. Only two papers specifically addressed the question of anaesthesia in CFS and in IEI. One paper suggested that volatile anaesthetics should be avoided in patients with IEI12 and the other described preoperative skin tests on six patients: three were allegedly sensitive to anaesthetic agents and anaesthesia was uneventful when these drugs were avoided.13 Although there was not a detailed description of the methods of intradermal testing, the dilutions used were stated, and they would be highly likely to produce false positives in non-allergic patients.
A further paper was found during a search on bronchospasm during anaesthesia.14 This described a woman with sick building syndrome who developed anaphylactic bronchospasm after propofol. This is the only report in the medical literature of an adverse reaction during induction or maintenance of general, regional, or local anaesthesia.
Two papers in scientific journals were retrieved from the Google but not the Ovid or PubMed search. The first paper described two patients with CFS, who received uneventful anaesthesia using subarachnoid block with heavy bupivacaine supplemented with propofol, fentanyl, glycopyrrolate, nitrous oxide, and isoflurane.15 The second described the procedures which needed to be instituted in the care of patients with MCSS in hospital.16 With respect to anaesthesia and surgery, the paper recommended that the anaesthetist be informed of the patient's medication sensitivities; that the procedure should be the first case of the day to minimize exposure; that ceramic or porcelain oxygen masks are indicated to avoid rubber; and that povidone-iodine is generally safe, but isopropyl alcohol should be used sparingly. Paper should be used for surgical dressings and latex-free gloves should be used.
The recommendations on the internet were based on those found on four special interest sites.17–20 The first notes that persons with CFS are hypersensitive to anaesthetics, often tolerating just a fraction of the standard dosage levels. Virtually every drug used in anaesthesia is described as a drug to be avoided on at least one site. In addition, user websites and discussion groups contained numerous anecdotes of adverse events suffered by people with IEI and CFS in hospitals with a number attributed to anaesthesia and surgery.
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Discussion |
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There are a number of problems which have been identified in patients with CFS and IEI that may be of relevance to the conduct of anaesthesia. Abnormal cardiovascular responses have been shown in a number of studies, and orthostatic hypotension is a postulated cause.21–24 Other studies have suggested that these patients do not differ significantly from controls25 and that orthostatic hypotension occurs in 45–76% of patients without either disorder in the first postoperative hour.26 The orthostatic hypotension is postulated to be related to autonomic dysfunction or the Chiari I malformation,27 although there is no evidence that this is more frequent in patients suffering orthostatic intolerance.27 A low circulating blood volume28 and impaired cerebral haemodynamics,29 including in younger patients,30 have also been described, but not verified by others.31 32 Magnesium deficiency33 has been implicated in CFS, but others have not found any association between magnesium deficiency and CFS.34 Hinds and colleagues35 concluded that there is no association between CFS and magnesium deficiency and that there is no role for magnesium therapy. The problems that are most relevant to anaesthesia are adverse drug responses and prolonged depressed consciousness, postoperative hypotension, and adverse drug reactions. The first two are easily managed and the major issue we have endeavoured to address is whether the adverse drug reactions can be prevented.
The immunological status of patients with CFS and IEI is complex and not well-characterized scientifically. Various studies have described T cell abnormalities including decreased T cell numbers,36 increased incidence of atopy,37 38 no increased incidence of atopy,39 increased delayed hypersensitivity allergy skin tests,40 no difference in allergen-specific IgE skin tests for common environmental allergens,41 decreased delayed hypersensitivity and immunoglobulin levels,36 no difference in IgE levels,42 and no immunological changes.43 It was noted in a review of evidence for immunological dysfunction in CFS that there was ‘remarkable inconsistency of results for each of the immunological parameters that were reported by the various laboratories’.44
There is, however, insufficient information to determine whether the adverse responses, which occur after operation, related to the anaesthesia, the surgery, or a combination of both. What is important is that neither our patients nor those in the literature demonstrate any evidence of adverse effects during induction or maintenance of anaesthesia, and there is no evidence that these patients are at risk from severe immediate reactions.
The complications that our patients had after operation are not those of allergy, and were usually characterized by symptoms and not signs. The symptoms and triggers in these diseases are diverse, and it would be surprising if any particular anaesthetic agent proved safer or more harmful than other agents. All of our patients have received agents contraindicated in the information reported on the internet.
Of most concern is the reported contraindications on the websites relating to the use of sympathomimetic drugs. There is nothing in the medical literature suggesting that these drugs are likely to be associated with adverse events, and it cannot be determined whether these recommendations are valid, or merely folklore. In the absence of hard evidence, the avoidance of potentially life-saving drugs may be potentially hazardous in itself.
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Conclusions and recommendations |
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Patients with IEI and CFS present a challenge to anaesthetists. The lack of information in the anaesthetic literature regarding the appropriate conduct of anaesthesia in patients with CFS and IEI suggests perhaps that anaesthetists may be a group who do not recognize them as either diseases or a problem. Patients with CFS and IEI frequently arrive with bizarre stories of past reactions, which do not fit conventional disease patterns, and lengthy lists of drugs, inhalants, foods, and chemicals, which precipitate symptoms. In Australia, they often produce documents from consumer groups or websites which suggest or dictate techniques to be favoured or drugs to be avoided. The most common document that accompanies patients in Australia presenting for anaesthesia is from a CFS website by Crean.17 The article warns against epinephrine in local anaesthetics, local anaesthetics, thiopental, histamine-releasing drugs, potentially hepatotoxic vapours, and anti-cholinesterases. Susceptibility to benzodiazepines, antihistamines, and psychotropic drugs is mentioned, as is a need to ensure levels of magnesium and potassium are adequate, and to hydrate before operation to prevent neurogenic hypotension. The site advocates preoperative skin testing to prevent anaphylaxis. The statement is made that patients with CFS are likely to experience fatigue and problems with memory longer than normal after operation. Propofol, fentanyl, and isoflurane are advocated.17 A further page on this site advises to discuss with their doctor whether they need to take extra vitamin A, D, and zinc after operation, avoid epinephrine, and elective surgery during exacerbations of the disease.18 None of the website recommendations contains references to scientific publications.
There are insufficient data to determine the appropriate conduct of anaesthesia for patients with CFS and IEI. The patients have a high incidence of problems with anaesthesia but rarely develop problems that require intervention. Our small study supported a possible benefit to hydration in the prevention of postoperative hypotension in patients with CFS.
Our experience with these patients, some over many years, leads to the following recommendations until a controlled prospective study is performed:
- It is inappropriate to engage in debate over the existence or otherwise of CFS and IEI before operation if a reasonable doctor–patient relationship is to be established.
- Patients should be encouraged to keep a diary containing information on drugs to which they have not had adverse responses, in addition to their usual lists describing adverse events. An anaesthetic diary should be encouraged as a help to subsequent anaesthesia. The downside of such an approach is to cement the belief that any response to anaesthesia in surgery is necessarily related to the drugs that are used.
- It is a good principle to avoid drugs that patients say they have had adverse responses to. Indeed, not to so do may place the anaesthetist in medicolegal jeopardy.
- Patients with IEI and CFS are often users of complementary medicines.45 46 A thorough history of intake of these substances should be taken before anaesthesia.
- There is a lack of rigorous scientific information to determine the ‘best’ way to provide a safe anaesthetic experience for these patients. Internet information is not scientifically supported.
- There is no evidence that patients with CFS and IEI are more likely to have anaphylactic or other life-threatening adverse drug reactions related to anaesthesia than patients who do not have such a history. There is no evidence that routine preoperative intradermal testing or other allergic/immunological investigation reactions in these patients reduce the risk of adverse drug reaction during anaesthesia and no evidence to support the use of such testing in the absence of a history of previous adverse response.
- There is a high incidence of adverse effects of anaesthesia and surgery in patients with CFS and IEI. These adverse effects characteristically are manifested by symptoms and not signs and often occur after patients are discharged. These symptoms may be new or exacerbations of the condition but are likely to be self-limiting, unlikely to respond to pharmacological treatment, and will invariably resolve.
- It is not known whether any particular anaesthetic drugs are more likely than others to produce problems.
- As many of our patients had a history of problems with metabisulphite, there is logic, albeit perhaps based on medicolegal rather than scientific considerations, in avoiding solutions containing metabisulphite in patients who complain that symptoms are precipitated by metabisulphite or other food additive allergy. On a similar basis, patients whose symptoms are precipitated by inhaled solvents and petrochemicals may be better without volatile agents. Drugs which patients identify as those to which they have had adverse responses should be avoided where possible. As few drugs as possible should be used.
- The anaesthetist should carefully consider patients’ demands. Permitting their own food, for example, saves problems with nursing and dietary staff. Whether particular patient requests are implemented probably relates more to kindness and harmony than to science. It must be said, however, that demands for the use of treatment known to be inappropriate should be resisted.
- Preoperative attendance at general anaesthetic clinics may benefit in that the patient may be advised that anaesthesia is safe, but that there is a slight risk of postoperative problems which will not be severe. In addition, the patient could be encouraged to keep an anaesthetic log book, which may guide future anaesthetists in the selection of drugs.
- In our view, the anaesthetist is almost certainly best to administer the same anaesthesia he/she would normally administer to a patient without CFS or IEI, as there is no evidence to support these patients being at greater risk than ‘normal’ patients from any particular drug. Indeed, we postulate that it is likely the absence of identifiable problems in the scientific literature is because the experience of anaesthetists with these patients is that they do not see major problems.
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