Epidermolysis bullosa is an uncommon hereditary disease, which is characterized by excessive susceptibility of the skin and mucosa to separate from the underlying tissues after even trivial mechanical trauma . Patients with epidermolysis bullosa may have multiple medical problems, but anaesthesia is made particularly difficult by the oropharyngeal and skin involvement, rendering airway management hazardous and maintenance of skin integrity a problem. There is a paucity of data in the literature concerning the perioperative management of children with epidermolysis bullosa. Therefore, we present data on anaesthetic management and complications from 56 procedures performed at our institution over the past 20 years.
The case notes and anaesthetic records of children, who had surgery at Our Lady’s Hospital for Sick Children, Dublin, Ireland, between 1979 and 1999 were scrutinized to determine their anaesthetic management and to record any complications that occurred. This hospital is a national referral centre for epidermolysis bullosa.
From January 1979 to January 1999, 16 children with epidermolysis bullosa were admitted to the hospital. Of these, 10 underwent a total of 56 anaesthetics. Of the patients who underwent surgery 70% were males and 70% had the dystrophic form of epidermolysis bullosa. The remainder had epidermolysis bullosa simplex (localized, generalized or herpetiformis). Mean age at time of procedure was 12.6 years; the youngest patient to have a general anaesthetic was 2 weeks’ old and the oldest was 18 years of age.
A total of 58 surgical procedures were performed on 56 occasions. On two occasions two different procedures were carried out under the same anaesthetic. Table 1 lists the surgical interventions in order of their frequency. Multiple procedures were carried out on these children, a minimum of one and a maximum of 26 interventions on an individual child. Patients with dystrophic epidermolysis bullosa had surgery consequent upon the sequelae of the disease, whereas the surgical procedures carried out in children with epidermolysis bullosa simplex were either diagnostic (skin biopsy, EUA airway) or unrelated to the underlying condition (tonsillectomy).
Children were premedicated in 22% of cases. Table 2 shows the drug and the route used. Premedication was administered orally or per rectum, with no reports of trauma or adverse effects after the latter route. Of note the rectal route was used only up to 1991.
Three children had EMLA (eutectic mixture of local anaesthetic) cream applied on the skin without an occlusive dressing with no recorded complications. Preoperative blood tests were often omitted in order to minimize trauma to the skin and blood samples were taken intraoperatively, under anaesthesia when absolutely necessary. Three children were receiving long-term corticosteroid therapy at the time of surgical procedure and they were given intravenous (i.v.) hydrocortisone.
A total of 54 general anaesthetics and two local anaesthetics (infiltration for removal of naevus and for gastrostomy) were administered. In two cases general anaesthesia was supplemented by local anaesthesia (metatarsal block for removal of ingrown toenail and local infiltration for tooth extraction). No complication was documented after either local technique.
The method of induction used is shown in Table 3. Inhalational induction was the preferred method in the majority of cases (75.5%) mainly by facemask, occasionally by hand. However, i.v. access was subsequently secured in 52% of patients with the precise site of insertion recorded in 78% instances. The preferred site of insertion was the antecubital fossa (45%), followed by the dorsum of the hand (23%), forearm and external jugular (14% each), and finally the leg (4%). Cannulae were secured by wrapping Vaseline™ petroleum gauze or non-adherent silicone dressing (Mepitel™) over and around the cannula followed by a light crepe bandage. Occasionally i.v. cannulae were sutured in place (18%). Tourniquets were avoided; venous stasis was achieved by manual venous occlusion.
Halothane and sevoflurane were the most commonly used inhalational induction agents. Maintenance of anaesthesia was usually with halothane and isoflurane, although sevoflurane was also used. Neuromuscular blockade was required infrequently. Succinylcholine was used on four and atracurium on nine occasions. No problem with the use of these drugs or with antagonism of neuromuscular block was recorded.
The duration of anaesthesia is shown in Figure 1. No record of time was found in two cases. The mean duration of anaesthesia was 64 min.
Figure 2 shows the frequency with which different methods of airway control were used. In 30% of patients the airway was managed using a facemask with the cushion covered with Vaseline™ or Vaseline™ gauze. Similarly the anaesthetist’s hands were covered with Vaseline™ in order to reduce friction to a minimum. In 5% of cases the airway was maintained by the anaesthetist’s hand cupped around the fresh gas outlet. No complications were observed.
The trachea was intubated in 65% of patients. The main indication for intubation was the need to share the airway with the surgeon during dental and gastrointestinal procedures. Intubation was achieved orally on 33 occasions and nasally on two. The laryngoscope blade and the appropriate sized endotracheal tube were both lubricated in an effort to minimize trauma; a lubricated McCoy laryngoscope blade was electively used in one case. At laryngoscopy the majority of cases were found to be Cormack and Lehane grade I or II . A bougie was required in a patient with grade III, and a Macintosh curved blade laryngoscope was changed to a Miller straight blade laryngoscope on one occasion in order to lift the thickened epiglottis. These two patients qualified for difficult intubation. However a ‘thick epiglottis’ was recorded on two occasions and an epiglottic bulla in one case.
The endotracheal tube was either unsecured, but padded with Vaseline™ gauze, or secured in place with a tie (ribbon gauze) or in case of a North facing nasal RAE (Ring, Adair and Elwyn) tube (Mallinckrodt Medical, Athlone, Ireland), simply covered with a circular net.
Figure 3 displays the frequency of individual monitoring or in different combinations. On five occasions (9.2% of patients) clinical observation alone was used. Pulse oximetry was the most frequent monitoring modality [65% of cases alone and 24% in combination with an electrocardiograph (ECG), non-invasive arterial pressure (NIBP), or both]. Of note, of the remaining 11% cases 7% had been completed before the pulse oximetry era (between 1979 and 1985) and 4% were rather short anaesthetics for procedures, e.g. change of dressing or revision of gastrostomy. NIBP monitoring was the least employed monitoring device, never used alone and only in eight cases in combination with SPO2, or ECG, or both. Care was taken on each occasion when the monitors were attached to the skin, i.e. the skin underneath the NIBP cuff was wrapped in Jelonet™.
Intraoperative analgesia was administered in 13 of 54 cases. Of these, six received i.v. morphine, four i.v. fentanyl, three local anaesthetic infiltration and only one a diclofenac suppository. Postoperative analgesia consisted mainly of oral non-steroidal anti-inflammatory drugs, i.e. mefenamic acid, and paracetamol. In one case an i.v. infusion of morphine was used.
Table 4 shows the incidence of perioperative complications associated with anaesthesia. Postoperative nausea and vomiting was reported in seven cases. In all cases there was evidence of oesophageal disease. New blisters were reported in three patients. Two blisters were lingual, presumably associated with a relatively difficult tracheal intubation (Cormack and Lehane grade II), whereas one occurred on the right shoulder where an ECG electrode had been placed. No complication was reported in the epidermolysis bullosa simplex group.
Epidermolysis bullosa is the name given to a group of rare, genetically determined disorders characterized by mucocutaneous blistering and subsequent scarring. Several variants have been established, which can be grouped into three broad categories: epidermolysis bullosa simplex, junctional epidermolysis bullosa and dystrophic epidermolysis bullosa [1,3].
Epidermolysis bullosa simplex or ‘epidermolytic epidermolysis bullosa’ is characterized by mechanically induced blistering occurring within the epidermis itself as a result of lysis of basal keratinocytes. Almost all forms of epidermolysis bullosa simplex are inherited as autosomal dominant traits. The prevalence of different forms of epidermolysis bullosa simplex can only be estimated and probably varies from one country to another, i.e. 10–20 per million for epidermolysis bullosa simplex localized to the hands and feet, 2 per million for generalized epidermolysis bullosa simplex and 5–10 per million for epidermolysis bullosa simplex herpetiformis. Generally the prognosis in epidermolysis bullosa simplex is good, the great majority of patients having a normal life expectancy. While epidermolysis bullosa simplex herpetiformis can undoubtedly be lethal in early infancy, the blistering tendency tends to decrease with time. However, some patients remain substantially disabled throughout their lives, particularly as a result of persisting blistering of the hands and feet, and palmar and plantar keratoderma.
Junctional epidermolysis bullosa comprises a group of inherited disorders characterized by mechanically induced blistering occurring within the basement membrane at the level of the lamina lucida. To date, all types of junctional epidermolysis bullosa have been transmitted as autosomal recessive traits. Because most affected individuals die early in life, the incidence of junctional epidermolysis bullosa is particularly difficult to ascertain. It has been estimated to be around 20 per million, the same as for epidermolysis bullosa simplex. From the clinician’s point of view it is currently practical to consider three broad groups of patients: (a) lethal junctional epidermolysis bullosa (Herlitz subtype), in which death is probable within the first 2 years of life, mainly due to laryngeal involvement or overwhelming sepsis; (b) benign junctional epidermolysis bullosa (non-Herlitz subtype), in which many patients will survive into adult life; (c) junctional epidermolysis bullosa with pyloric atresia, usually with death in infancy and only occasional survivors.
Dystrophic epidermolysis bullosa or ‘dermolytic epidermolysis bullosa’ is a group of inherited disorders characterized by mechanically induced blistering occurring immediately below the lamina densa of the basement membrane zone. These disorders derive the name dystrophic from the tendency of the blisters to heal with atrophic scarring. Dystrophic epidermolysis bullosa may be inherited as an autosomal dominant or an autosomal recessive trait. In general, it tends to be most severe when inherited as a recessive, and mildest when inherited as dominant, but there is considerable clinical overlap. A recent estimate from Scotland quotes the prevalence of dystrophic epidermolysis bullosa at 21.4 per million [http://www.debra.org.uk]. Dystrophic epidermolysis bullosa reflects mutations in the gene for type VII collagen (known as COL7A1). Type VII collagen is a major component of anchoring fibrils that anchor the lamina densa within the superficial dermis. This structural abnormality affects the stratified squamous epithelium of the skin, oropharynx and oesophagus, whereas the ciliated columnar epithelium of the larynx and trachea is spared. There is an extraordinary variation in prognosis in dystrophic epidermolysis bullosa. Patients with the mildest clinical presentations will enjoy early cessation of blistering, occasionally even in the first year of life. On the other hand, more severely affected individuals will experience increasing malnutrition, anaemia, and progressive disability due to interference with joint mobility. There is little in the way of drug therapy (phenytoin, protease inhibitors, retinoids, tetracyclines, corticosteroids and vitamin E) to reduce the incidence or severity of the bullae and surgery is important in the prevention of serious debilitating sequelae. Often multiple surgical procedures are required.
While teeth are usually structurally normal in dystrophic epidermolysis bullosa, they are prone to severe caries . A conservative dental approach seems to be most common despite the occasional recommendation for wholesale extraction. The possession of teeth is helpful in giving the patients a more normal facial appearance, since dentures are not tolerated. Undoubtedly, extraction is sometimes the only practical option for severely carious teeth because of the difficulty of doing conservative dental work through these patients’ very restricted mouth opening. Where extraction is necessary, healing is rapid. However, a link between restoration of dental health and the ability to chew effectively in the presence of oesophageal strictures can be important. When extensive dental work is carried out feeding via a nasogastric tube may be needed for 24–48 h postoperatively.
Dribbling often occurs in children with dystrophic epidermolysis bullosa, mainly due to obliteration of the lingual and inferior gingivo-buccal sulci. This can be successfully corrected by surgical relocation of the submandibular salivary ducts to the base of the tongue. These patients also suffer blistering to mucosal membranes. If swallowing difficulties become more constant, it may occasionally be beneficial to release the buccal mucosa, to allow fuller opening of the mouth. Improved access to the mouth is sometimes necessary for anaesthesia and dental work, but because these procedures also mobilize the tongue, they have the additional benefit of making it much easier for the patient to masticate, swallow and talk. Mouth opening can also be improved by exercise.
Oesophageal strictures are thought to occur twice as often in women as in men . There is a risk of regurgitation or reflux and therefore of pulmonary aspiration. Oral verapamil has been advocated to alleviate oesophageal dysmotility and spasm. The improvement is short-lived and verapamil will generally exacerbate the constipation, which is already a major problem in most patients. Surgical procedures include balloon dilatation of the oesophagus or endoscopy and oesophageal bougienage. Patients frequently report that improvement may be short-lived, with the intervals between subsequent dilatations tending to become progressively briefer. Intraoperative deaths due to rupture of the oesophagus have been reported, even from centres familiar with this type of intervention. More radical procedures have included oesophageal reconstruction by reversed gastric tube, resection and end-to-end oesophageal anastomosis and colon transplant. Favourable results at 5-year follow-up have been reported, but the number of patients so treated has been small, and the associated risks are substantial.
Insertion of gastrostomy carries several benefits in terms of feeding, amelioration of constipation and improved compliance with medicines and with vitamin and mineral supplementation. Gastrostomy insertion should be considered in preference to more invasive surgical procedures in children with dystrophic epidermolysis bullosa in whom dysphagia compromises nutritional intake . Persistent constipation or marked anal pain on attempted defecation may be an indication for anal stretch under general anaesthesia .
Scarring of the skin and soft tissues leads to contractures and fusion of fingers and toes causing syndactily [1,5]. Corrective surgery should be undertaken as soon as the function of the hand is significantly impaired. Function is mainly compromised by flexion and by fusion of the first interdigital web.
Thickened, dystrophic finger and toenails may be extremely unsightly; in the case of toenails, they may interfere with wearing shoes, therefore such nails should be permanently removed surgically . In later life, malignant degeneration of stratified squamous epithelium may occur. Wide excision and split skin grafting in some patients is required. Facial trauma and scarring classically result in microstomia narrowed nasal apertures and poor eyelid retraction (so that corneal damage is not uncommon and may occur during surgery). Surgical correction may be necessary to improve mouth opening and permit eyelid closure .
Certain precautions and meticulous attention to detail is required throughout if anaesthetic related morbidity is to be avoided . All those involved in handling these children before, during and after surgery must be made aware of the extreme vulnerability of their skin . An epidermolysis bullosa liaison nurse is invaluable in this regard.
During the preoperative assessment a full history should be obtained and patient’s previous anaesthetic records reviewed [5–7]. Co-existing problems should be assessed, in particular signs of anaemia, gastro-oesophageal reflux, infection and malnutrition.
Anaemia is present in most patients with severe dystrophic epidermolysis bullosa. Investigations demonstrate haematological features both of iron deficiency and of decreased red cell iron utilization (anaemia of chronic disease). The iron deficiency probably reflects both chronic blood loss from skin, mouth, oesophagus and anal canal, and poor iron intake . However, in our experience this has not been a problem because of the minor blood loss associated with the surgical procedures performed. Preoperative blood tests were often omitted or taken under general anaesthesia when necessary.
Antacid prophylaxis may be required if there is a history of reflux, regurgitation or a confirmed oesophageal stricture. Because gastro-oesophageal reflux is so common in this population group, they may already be receiving a H2 receptor-blocking drug [4,8].
Infection, especially with common commensals such as staphylococci and β-haemolytic streptococci, are not unusual as patients often have both poor cellular and humoral immunity and may also have had long-term corticosteroid treatment. Perioperative treatment with hydrocortisone may be required in this case in order to compensate for any adrenal suppression .
The malnutrition, which occurs in severe dystrophic epidermolysis bullosa, is a consequence of a combination of decreased nutritional intake and increased requirements as a result of blood and plasma loss from denuded epithelium, skin infection and continuous wound healing. This can exert a major detrimental impact on electrolyte balance, wound healing, resistance to infection and mortality .
Sedative premedication can be useful in younger patients to avoid restlessness and injury; however, older children are often best brought to theatre fully awake so as to assist in positioning . EMLA cream has been successfully applied in a number of cases in our series of patients, but no adhesive dressing was used and great care was taken in wiping away any residue.
In general, management of patients with epidermolysis bullosa is one of a ‘no touch’ principle. However, direct pressure to the skin is not as damaging as frictional or shearing forces. All persons involved in handling these children before, during and after surgery must be made aware of the extreme vulnerability of their skin. Patients must be moved about with great care. Trolleys and operating tables should be well padded so that pressure on the skin is kept to a minimum. Ideally patients should place themselves on the operating table. Domestic Clingfilm™ (Tesco Clingfilm, Tesco Stores Ltd, Cheshunt, UK) is very useful to place under the child to reduce shearing forces and to prevent adherence; it is also valuable as a temporary covering for eroded areas when dressings are removed. Sticky tape and other adhesive materials must be avoided, as the skin will peel away when they are removed. Mepitel™ has proved very valuable for securing devices such as i.v. cannulae, as its adhesive properties hold the device securely, but, in contrast to adherent tapes, removal does not cause any damage to the skin. Non-adhesive elasticated netting, conforming bandages and sutures if necessary, may also be useful . In our series three i.v. cannulae were sutured in place in the antecubital fossa with no reported complication. However, we prefer the method of wrapping Vaseline™ petroleum gauze (Sherwood Medical, St Louis, USA) or non-adherent silicone dressing (Mepitel™, Monlycke, Goteborg, Sweden) over and around the cannula followed by a light crepe bandage. Because all these products are now readily available securing i.v. access is less of a problem than formerly, therefore we now try to insert an i.v. cannula in all cases whenever possible. Care must be taken to protect the eyes. Griffin and Mayou reported a high incidence of corneal damage in patients reviewed after anaesthesia . The incidence of such injury has decreased to zero in the present series. Lubricants such as simple eye ointment British Pharmacopoeia (10% liquid paraffin, wool fat 10%, in yellow soft paraffin) are used abundantly as soon as the patient is anaesthetized; the eyes are carefully closed and covered with Vaseline™ gauze. Oxygen masks should be avoided in recovery because the sharp edges can damage the skin. Children with epidermolysis bullosa can be distressed on waking and struggle, causing skin damage; the mothers should be present in recovery to reassure them on waking.
Minimal monitoring, advocated by the Association of Anaesthetists of Great Britain and Ireland , is not always possible so that these patients are often poorly monitored . Pulse oximetry is the preferred method of monitoring heart rate and there are no complications reported with its use. Whereas ECG monitoring was mostly used in the early days, SPO2 seems to be used as a sole monitor for short procedures or in combination with non-invasive arterial monitoring for the more complex ones. Electrocardiogram monitoring is difficult because the adhesive pads can cause trauma at application or removal. Blistering to the shoulder in one patient in our series was due to an ECG application. Different methods of ECG monitoring have been described [5,6,9,10]. The adhesive pad can be removed and the electrode placed beneath the patient to obtain good contact and provide a reasonable waveform. A further adaptation is to place the adhesive electrodes on the underside of a chest radiograph over suitably placed holes; the patient is then placed on the film. Hagen and Langenberg used ECG needle electrodes and secured them by means of a circumferential elastic bandage . Ames and his colleagues advocate the placement of the adhesive electrodes on to three jelly defibrillation pads normally used for cardioversion. These pads are not adhesive and when laid in the CM5 configuration remain in place and give excellent electrical contact. If traction is applied to the leads they simply glide across the pad or else the pad lifts off the skin without trauma . Despite the potential for blistering beneath the cuff, non-invasive arterial pressure monitoring and tourniquet can be used with plenty of non-adherent soft gauze padding such as a Melolin™ roll. Intra-arterial blood pressure monitoring previously recommended as the measurement of choice is difficult to use because of scarring over the wrist.
General anaesthesia is our technique of choice and this is supported by a very low incidence of complications. As these patients undergo repeated anaesthetics, they have often formed their own preference for the anaesthetic that best suits them. Venous access is invariably difficult and therefore inhalational induction is popular. In our series halothane was used for induction in 44.4% and for maintenance in 50% of cases, whereas sevoflurane was used in 28% for induction and 9.3% for maintenance (however, latterly sevoflurane is mostly used). Isoflurane was used for induction in one patient and for maintenance in 40.7% of cases. For i.v. induction, propofol was used in 11% of cases and thiopental in 13%. No problems were reported. Thiopental was once thought to be relatively contraindicated, as many believed that porphyria was closely linked with epidermolysis bullosa . This has long since been disproved . Ketamine has been advocated in the past as an induction agent , but excitation on recovery could cause further trauma. Concerns that succinylcholine could lead to trauma and the hyperkalaemic response in patients with dystrophic muscle have not been confirmed. Twenty-two of 35 tracheal intubations in our series were performed without any muscle relaxant. Succinylcholine was used in four patients and atracurium in nine with no adverse effects.
The first issue beyond safely maintaining an airway is avoidance of further bullae developing. To avoid undue facial manipulation, intubation is generally preferable [13–16], and an uncuffed endotracheal tracheal tube should be selected, a size smaller than one would normally use. The tracheal tube and laryngoscope blade should be well lubricated. The tube should be fixed using ribbon gauze. All tubing should be padded, and where it touches the lips or skin, Vaseline™ gauze should be interposed. Facemasks can be used safely but must be prepared by several layers of Vaseline™ gauze. More gauze must be placed beneath the anaesthetists’ fingers while applying minimal chin lift. The airway is not inherently difficult to maintain, because the tongue is often small and scarred and does not fall back into the pharynx. Lubricated oral airways can be used with care, but are seldom necessary. Several reports have supported the use of the head box . Its use is complicated by poor airway control, no protection against aspiration and problems with hypoventilation. An endotracheal tube was used to secure the airway in 65% of cases. A preformed RAE tube was used in one-third of these (12 oral and 1 nasal), because we found it easier to keep in place even when untied. A well-lubricated McCoy laryngoscope blade was electively used on two occasions in order to reduce airway trauma.
Despite all the precautions taken, we noted two cases in which lingual bullae occurred as a direct result of airway manipulation. Tracheal lesions appear not to occur after intubation probably because the trachea is lined with columnar epithelium .
Difficult intubation was found on two occasions. On one occasion a straight bladed Miller laryngoscope was required to lift the thickened epiglottis and on the other a well-lubricated bougie was used carefully without complications. Cricoid pressure can be used, provided that it is applied evenly and with no sideways movement. During extubation, oropharyngeal suctioning can lead to life-threatening bullae formation , therefore it is best avoided.
Ames and his colleagues describe the safe use of a size smaller than normal laryngeal mask airway with the shaft and cuff lubricated. Although the cuff should be inflated to maintain its shape it does not need to be absolutely secure within the pharynx, and therefore there should be a leak. Vaseline™ gauze should then be wrapped around the tube at the mouth in order to minimize trauma to the lips and to weigh the mask down in situ. Particularly in children, removal of the laryngeal mask is strongly recommended before the patient awakes so as to minimize trauma to the airway and teeth.
Patients of all ages with epidermolysis bullosa experience a great deal of pain, predominantly from cutaneous ulcerations, particularly at times of dressing changes, from oropharyngeal ulceration, and from anal fissures, particularly at the time of defecation . Pain from the skin can be minimized by the choice of the most appropriate dressings; Mepitel™ is extremely valuable from this point of view, as daily changes are unnecessary. Similarly pain from the oropharynx can be reduced by provision of a gastrostomy in selected cases, and pain on defecation can be minimized by keeping the faeces soft. Drugs such as paracetamol (20 mg kg–1), codeine (0.5–1 mg kg–1) and morphine (0.2–0.5 mg kg–1) are often helpful if given orally in anticipation of the pain predictably associated with dressing changes or surgical procedures. For intra- and postoperative pain relief i.v. opioids (morphine and fentanyl) were our drugs of choice (73% of cases). In 9% of patients diclofenac suppositories were used without complaint.
Regional anaesthesia was initially proposed in 1966 as an alternative to general anaesthesia in dystrophic epidermolysis bullosa; however, the suggestion was not taken up based on the fear of causing new bullae formation. In current practice regional anaesthesia in combination with a general anaesthetic is useful for postoperative pain control, particularly for limb and dental surgery . In our series it was used in 18% of cases without complications. The technique is standard, but the site should be inspected for lesions, and compression distal to the point of injection should be avoided. The skin should be cleaned with antiseptic sprays. Although subarachnoid and epidural anaesthesia in patients with epidermolysis bullosa has been reported  we have not used them in our institution. Oral medication after surgery is best given in the effervescent form, as many of these patients find swallowing difficult.
In conclusion, the patient with epidermolysis bullosa represents a formidable challenge to the anaesthetist. Treatment in specific units allows accumulation of experience by the many specialties involved. Patients are best managed by a multidisciplinary team including a consultant anaesthetist trained in fibreoptic intubation, who deals with them on a regular basis. However, patients with epidermolysis bullosa may need anaesthesia outside a specialist centre, for procedures often unrelated to their disorder, such as general surgery or obstetrics. Morbidity could be reduced by education of theatre staff about skin care and by extensive use of aspiration prophylaxis. With maximal skin and mucous membrane protection, anaesthesia for procedures in children with epidermolysis bullosa may be undertaken with few sequelae.