398
ANESTHESIA AND ANALGESIA . . , Current Researches VOL.56, No. 3, MAY-JUNE, 1977
Ketamine Anesthesia in Dermolytic Bullous Dermatosis (Epidermolysis Bullosa) S. R. LoVERME, MD, FACS* A.
T. OROPOLLO, MD, FACAt
An unusual hereditary disease entity of the integument, dermolytic bullous dermatosis (epidermolysis bullosa dystrophica), recessive type, is presented. The disease is characterized by the formation of bullae, vesicles, and erosions upon the application of the least trauma. Healing results in scarring and incapacitating deformities which require extensive reconstructive surgery.
A technic utilizing ketamine-diazepam “dissociative anesthesia” for several surgical procedures for this condition is described. The technic enabled the patient to undergo 3 complex operations over a 2-year period with minimum complications.
T a
encompass the following major types of classic epidermolysis bullosa: $
HIS paper presents experiences in the anesthetic and surgical management of case of dermolytic bullous dermatosis, recessive type (epidermolysis bullosa dystrophica polydysplasia) . In view of the uniqueness of this entity, 1:300,000 for this particular type,l a brief review of some of its features is submitted.
The disorder is one of the mechanobullous diseases.2 These are rare, chronic, noninflammatory conditions in which the clinical lesions, erosions, or bullae frequently arise from relatively minor trauma to skin or mucous membranes. They are primarily inherited, although acquired, mild forms have been described.2
A recent classification2 of the diseases divides them into 2 major divisions, the nonscarring and the scarring. These divisions
I . Nonscarring. A. Epidermolysis bullosa simplex is the most common and mildest form. The lesions may be present at birth or at any time thereafter. They heal rapidly and without scarring. Longevity is normal and inheritance is dominant. B. Recurrent bullous eruptions of hands and feet (Weber-Cockayne diseases) is noted early in life and primarily involves the extremities. Many cases occur only in summer. The lesions generally heal without scarring and the disease does not impair the general health. $Terminology varies; that proposed by Pearson? is used here. E d .
”Clinical Professor of Plastic and Reconstructive Surgery, New Jersey College of Medicine and Dentistry, Newark, New Jersey 07102. tDirector, Department of Anesthesia, Montclair Community Hospital, Montclair, New Jersey. Paper received: 7/18/75 Accepted for publication: 9/24/76
.
Dermolytic Bullous Dermatosis . . LoVerme and Oropollo
C. Junctional bullous epidermatosis (epidermolysis bullosa letalis, Herlitz disease4) is the most severe form and is a result of recessive inheritance. The lesions are extensive, commonly arise at birth, and usually heal with no scar formation. Survival is rare beyond 3 months.
ZZ. Scarring. A. Dermolytic bullous dermatosis (epidermolysis bullosa dystrophica hyperplastic), with a dominant inheritance, is a moderately severe form in which scarring results from the healing of bullae. Contractures may occur, but the disease does not pose a threat to the patient’s longevity. B. Dermolytic bullous dermatosis (epidermolysis bullosa dystrophica polydysplasia) is transmitted by recessive inheritance. This type is severe and extremely disabling. It is present at birth or appears early in infancy with the formation of widespread bullae of the skin and oral mucosa. These are produced by minor trauma. The skin is thin, xerodermic, and presenile in appearance. There may also be associated defects of the nails, teeth, mucous membranes, and conjunctiva. The oral lesions produce scarring and degenerative changes of the mucosa, with varying degrees of stenosis of the alimentary track, such as esophageal stenosis. Because of the predilection for hands, feet, elbows, and knees, severe mutilation may result. There is extensive scarring, with the production of pseudodactyly and contractures of the hands. General physical and intellectual development is poor and survival beyond the 2nd decade is unusual. The survival rate has increased with the more effective control of infections.
399
with split or full-thickness grafts, are therefore used.6~7 In these patients, anesthesia presents a serious and difficult endeavor.8-15Any friction on the skin and mucous membranes can produce large bullae. Application of a mask may produce bullae, scarring, and deformity. Oral airways can produce hemorrhagic lesions of the tongue. Endotracheal intubation may result in the formation of lesions of the oropharyngeal epithelium capable of producing acute obstruction of the upper airway. Bullae within the larynx extending down the trachea, resulting in obstruction and even stenosis, have been reported.7 Adhesive tape has caused the underlying skin to be lifted off the patient.
CASE REPORT In the recent past, we have treated an intelligent, alert, and cooperative 17-yearold girl, with severe hand deformities noted since childhood, secondary to epidermolysis dystrophica. Her skin had a shiny, parchment-like appearance and the nails were absent. Numerous bullae, scars, and excoriations were noted over the entire body surface, but particularly involving the extremities and the perioral area. The fingers were in flexion contracture of varying degree, bound together with loss of web spaces, and the thumbs were adducted into the other fingers (fig 1).The wrists showed some flexion deformity, with the left wrist being the more contracted. The feet were also involved, but not to the degree of the hands.
The etiology of these diseases is unknown. The basic pathologic defect is a separation of the epidermis from the underlying corium on slight trauma.5 Innumerable systemic drugs have been employed in treating this disorder, all without marked success. Steroids have been helpful, but are of limited value. Because of the marked impairment of function, often to the point where everyday functions are impossible or severely hampered, surgical intervention is often necessary. operative procedures undertaken are usually for (1) the release of epithelial contractures of the digits; (2) the restoration of opposition and pinch; and (3) to allow for unrestricted growth. Simple separations of the digits,
FIG 1. Stigmata of dermolytic bullous dermatitis, recessive type, in hands of 17-year-old patient. No stigmata were seen in any other members of family.
400
ANESTHESIA AND ANALGESIA . . . Current Researches VOL.56, No. 3, MAY-JUNE,1977
In view of the many complications possible with general anesthesia, it was elected to employ a “dissociative anesthesia,” ketamine hydrochloride, as the sole anesthetic agent.Is This drug appeared to be an ideal agent in this case, since it provided for a rapid induction with good analgesia, maintenance of a good airway with preservation of the pharyngeal-laryngeal reflexes, and minimal manipulation of the patient. To reduce the possibility of “emergence delirium,” sometimes seen after ketamine anesthesia, diazepam was given as a premedicant, at the termination of operation, and in the recovery period. She had had previous operations under general inhalation anesthesia, but some difficulties were encountered with the technic, and postoperative restlessness had produced numerous new bullae and erosions of the patient’s skin. The patient and parents were seen preoperatively, and the anesthesia management was discussed at length. In a period of 2 years, the patient underwent 3 surgical operations, consisting of multiple corrective procedures of the hands. The anesthetic management was identical in all respects, using the diazepam-ketamine I V technic for induction, maintenance, and emergence. On admission, her weight was 44 kg, height 173 cm, pulse 96 bpm, oral temperature 37” C, BP 110/70. All laboratory findings were within normal limits. On the day of operation, the patient was premedicated with 0.4 mg of atropine and 10 mg of diazepam IM 45 minutes prior to operation. She was alert and calm on arrival in the operating suite. A balanced electrolyte solution, Normosol-R@/5 percent DW, was begun with a #18 Jelco needle. Metal needle electrodes, #25, were used intradermally in conjunction with the use of an ECG monitor. No adhesives were employed. During an earlier procedure, the removal of adhering paper electrodes caused the underlying skin to be detached, producing weeping circular lesions (fig 2 ) . A bland ointment was used to protect the eyes. Induction was with ketamine (I00 mg) IV given over a period of 1 minute; supplementary doses, when required, were given at one-half the induction dose. Pulse and respiratory rates were increased slightly. Blood pressures were not taken because of the risk of skin damage. Reconstructive surgery on the right hand was performed and anesthesia was maintained uneventfully for
FIG2. Lesion caused by electrode, after removal. Same patient as figure 1.
a little over 4 hours. Approximately 15 minutes before the completion of operation, the patient was given 2.5 mg of diazepam IV. She was then moved to the recovery room, where reoovery was rapid and uneventful and consciousness was regained after approximately one-half hour. There was no evidence of emergence delirium. Postoperative visits revealed a complete absence of dreaming or mental agitation during recovery.
REFERENCES 1. Davison BCC: Epidermolysis bullosa. J Med Genet 5:189-196, 1968 2. Pearson RW: The mechanobullous diseases (epidermolysis bullosa), Dermatology in General Medicine. First edition. Edited by TB Fitzpatrick. New York, McGraw-Hill Book Company, 1971, pp 621.643
3. Cockayne EA: Recurrent bullous eruption of the feet. Br J Dermatol 50:358-362, 1938 4. Herlitz G: ,Kongenitaler, nicht sypbilitischer Pemphigus. Eine Ubersicht nebst Beschreiburgeiner neuen Krankheitsform. Acta Paediatr 17:315-317, 1935
5. Pearson RW: The mechanobullous diseases (epidermolysis bullosa), Dermatology in General
Dermolytic Bullous Dermatosis
. . . LoVerme and Oropollo
401
Medicine. First edition. Edited by Tl3 Fitzpatrick. New York, McGraw-Hill Book Company, 1971, pp 635-639
10. Marshall RF: A comment on epidermolysis bullosa and its anesthetic management for dental operations. Br J Anaesth 35: 724-727, 1965
6. Crikelair GF, Hoehn FU, Domonkos AN, et al: Skin homografts in epidermolysis bullosa dystrophica. Plast Reconstr Surg 46:89-92, 1970
11. Pers M: Skin grafting in a case of epidermolysis bullosa. Acta Chir Scand 129:333-334, 1965
7. Rees TD, Swinyard CA: Rehabilitative digital surgery in epidermolysis bullosa. Plast Reconstr Surg 40: 169-174, 1967
8. Lee C, Nagel EL: Anesthetic management of a patient with recessive epidermolysis bullosa dystrophica. Anesthesiology 43: 122-124, 1975 9. Kubota Y, Norton ML, Goldenberg S, et al: Anesthetic management of patients with epidermolysis bullosa undergoing surgery. Anesth Analg 40:244-250, 1961
12. Wilson F: Epidermolysis bullosa: a rare disease of anaesthetic interest. Br J Anaesth 31: 26-31, 1959 13. Young DA, Hardwick PB: Anaesthesia for epidermolysis bullosa dystrophica. Anaesthesia 23: 264-267, 1968 14. Petty WC, Gunther RC: Anesthesia for nonfacial surgery in polydysplastic epidermolysis bullosa (dystrophic). Anesth Analg 49: 246-250, 1970 15. Corssen G, Gutierrez J, Reves JG, et al: Ketamine in the anesthetic management of asthmatic patients. Anesth Analg 51:588-596, 1972
VENTILATORY FAILURE. A n obese (52.9 k g ) 10-year-old boy manifested unexplained respiratory failure associated with almost complete absence of hypoxic and hypercapnic ventilatory responses. Weight loss to 38.2 k g did not a l t e r t h e responses to either hypoxia or hypercapnia. Neurologic examination, including normal ninthcranial nerve function illustrated by intact gag reflex and heart-rate slowing during carotid-sinus massage, w a s negative. Thyroid function tests were normal. Ventilatory responses to both hypoxia and hypercapnia were found t o be depressed in both parents and 4 siblings. It seems t h a t genetically determined reductions in chemical stimulation to ventilation are the most likely explanations f o r this patient’s ventilatory failure. (Moore GC, Zioillich CW, Battaglia JD, et al: Respiratory failiirc associated with familial depression of ventilatory response to hypoxia and hypcreapnia. N E J M 295: 861-865,1976)
ANESTHESIA AND ANALGESIA . . , Current Researches VOL.56, No. 3, MAY-JUNE, 1977
Ketamine Anesthesia in Dermolytic Bullous Dermatosis (Epidermolysis Bullosa) S. R. LoVERME, MD, FACS* A.
T. OROPOLLO, MD, FACAt
An unusual hereditary disease entity of the integument, dermolytic bullous dermatosis (epidermolysis bullosa dystrophica), recessive type, is presented. The disease is characterized by the formation of bullae, vesicles, and erosions upon the application of the least trauma. Healing results in scarring and incapacitating deformities which require extensive reconstructive surgery.
A technic utilizing ketamine-diazepam “dissociative anesthesia” for several surgical procedures for this condition is described. The technic enabled the patient to undergo 3 complex operations over a 2-year period with minimum complications.
T a
encompass the following major types of classic epidermolysis bullosa: $
HIS paper presents experiences in the anesthetic and surgical management of case of dermolytic bullous dermatosis, recessive type (epidermolysis bullosa dystrophica polydysplasia) . In view of the uniqueness of this entity, 1:300,000 for this particular type,l a brief review of some of its features is submitted.
The disorder is one of the mechanobullous diseases.2 These are rare, chronic, noninflammatory conditions in which the clinical lesions, erosions, or bullae frequently arise from relatively minor trauma to skin or mucous membranes. They are primarily inherited, although acquired, mild forms have been described.2
A recent classification2 of the diseases divides them into 2 major divisions, the nonscarring and the scarring. These divisions
I . Nonscarring. A. Epidermolysis bullosa simplex is the most common and mildest form. The lesions may be present at birth or at any time thereafter. They heal rapidly and without scarring. Longevity is normal and inheritance is dominant. B. Recurrent bullous eruptions of hands and feet (Weber-Cockayne diseases) is noted early in life and primarily involves the extremities. Many cases occur only in summer. The lesions generally heal without scarring and the disease does not impair the general health. $Terminology varies; that proposed by Pearson? is used here. E d .
”Clinical Professor of Plastic and Reconstructive Surgery, New Jersey College of Medicine and Dentistry, Newark, New Jersey 07102. tDirector, Department of Anesthesia, Montclair Community Hospital, Montclair, New Jersey. Paper received: 7/18/75 Accepted for publication: 9/24/76
.
Dermolytic Bullous Dermatosis . . LoVerme and Oropollo
C. Junctional bullous epidermatosis (epidermolysis bullosa letalis, Herlitz disease4) is the most severe form and is a result of recessive inheritance. The lesions are extensive, commonly arise at birth, and usually heal with no scar formation. Survival is rare beyond 3 months.
ZZ. Scarring. A. Dermolytic bullous dermatosis (epidermolysis bullosa dystrophica hyperplastic), with a dominant inheritance, is a moderately severe form in which scarring results from the healing of bullae. Contractures may occur, but the disease does not pose a threat to the patient’s longevity. B. Dermolytic bullous dermatosis (epidermolysis bullosa dystrophica polydysplasia) is transmitted by recessive inheritance. This type is severe and extremely disabling. It is present at birth or appears early in infancy with the formation of widespread bullae of the skin and oral mucosa. These are produced by minor trauma. The skin is thin, xerodermic, and presenile in appearance. There may also be associated defects of the nails, teeth, mucous membranes, and conjunctiva. The oral lesions produce scarring and degenerative changes of the mucosa, with varying degrees of stenosis of the alimentary track, such as esophageal stenosis. Because of the predilection for hands, feet, elbows, and knees, severe mutilation may result. There is extensive scarring, with the production of pseudodactyly and contractures of the hands. General physical and intellectual development is poor and survival beyond the 2nd decade is unusual. The survival rate has increased with the more effective control of infections.
399
with split or full-thickness grafts, are therefore used.6~7 In these patients, anesthesia presents a serious and difficult endeavor.8-15Any friction on the skin and mucous membranes can produce large bullae. Application of a mask may produce bullae, scarring, and deformity. Oral airways can produce hemorrhagic lesions of the tongue. Endotracheal intubation may result in the formation of lesions of the oropharyngeal epithelium capable of producing acute obstruction of the upper airway. Bullae within the larynx extending down the trachea, resulting in obstruction and even stenosis, have been reported.7 Adhesive tape has caused the underlying skin to be lifted off the patient.
CASE REPORT In the recent past, we have treated an intelligent, alert, and cooperative 17-yearold girl, with severe hand deformities noted since childhood, secondary to epidermolysis dystrophica. Her skin had a shiny, parchment-like appearance and the nails were absent. Numerous bullae, scars, and excoriations were noted over the entire body surface, but particularly involving the extremities and the perioral area. The fingers were in flexion contracture of varying degree, bound together with loss of web spaces, and the thumbs were adducted into the other fingers (fig 1).The wrists showed some flexion deformity, with the left wrist being the more contracted. The feet were also involved, but not to the degree of the hands.
The etiology of these diseases is unknown. The basic pathologic defect is a separation of the epidermis from the underlying corium on slight trauma.5 Innumerable systemic drugs have been employed in treating this disorder, all without marked success. Steroids have been helpful, but are of limited value. Because of the marked impairment of function, often to the point where everyday functions are impossible or severely hampered, surgical intervention is often necessary. operative procedures undertaken are usually for (1) the release of epithelial contractures of the digits; (2) the restoration of opposition and pinch; and (3) to allow for unrestricted growth. Simple separations of the digits,
FIG 1. Stigmata of dermolytic bullous dermatitis, recessive type, in hands of 17-year-old patient. No stigmata were seen in any other members of family.
400
ANESTHESIA AND ANALGESIA . . . Current Researches VOL.56, No. 3, MAY-JUNE,1977
In view of the many complications possible with general anesthesia, it was elected to employ a “dissociative anesthesia,” ketamine hydrochloride, as the sole anesthetic agent.Is This drug appeared to be an ideal agent in this case, since it provided for a rapid induction with good analgesia, maintenance of a good airway with preservation of the pharyngeal-laryngeal reflexes, and minimal manipulation of the patient. To reduce the possibility of “emergence delirium,” sometimes seen after ketamine anesthesia, diazepam was given as a premedicant, at the termination of operation, and in the recovery period. She had had previous operations under general inhalation anesthesia, but some difficulties were encountered with the technic, and postoperative restlessness had produced numerous new bullae and erosions of the patient’s skin. The patient and parents were seen preoperatively, and the anesthesia management was discussed at length. In a period of 2 years, the patient underwent 3 surgical operations, consisting of multiple corrective procedures of the hands. The anesthetic management was identical in all respects, using the diazepam-ketamine I V technic for induction, maintenance, and emergence. On admission, her weight was 44 kg, height 173 cm, pulse 96 bpm, oral temperature 37” C, BP 110/70. All laboratory findings were within normal limits. On the day of operation, the patient was premedicated with 0.4 mg of atropine and 10 mg of diazepam IM 45 minutes prior to operation. She was alert and calm on arrival in the operating suite. A balanced electrolyte solution, Normosol-R@/5 percent DW, was begun with a #18 Jelco needle. Metal needle electrodes, #25, were used intradermally in conjunction with the use of an ECG monitor. No adhesives were employed. During an earlier procedure, the removal of adhering paper electrodes caused the underlying skin to be detached, producing weeping circular lesions (fig 2 ) . A bland ointment was used to protect the eyes. Induction was with ketamine (I00 mg) IV given over a period of 1 minute; supplementary doses, when required, were given at one-half the induction dose. Pulse and respiratory rates were increased slightly. Blood pressures were not taken because of the risk of skin damage. Reconstructive surgery on the right hand was performed and anesthesia was maintained uneventfully for
FIG2. Lesion caused by electrode, after removal. Same patient as figure 1.
a little over 4 hours. Approximately 15 minutes before the completion of operation, the patient was given 2.5 mg of diazepam IV. She was then moved to the recovery room, where reoovery was rapid and uneventful and consciousness was regained after approximately one-half hour. There was no evidence of emergence delirium. Postoperative visits revealed a complete absence of dreaming or mental agitation during recovery.
REFERENCES 1. Davison BCC: Epidermolysis bullosa. J Med Genet 5:189-196, 1968 2. Pearson RW: The mechanobullous diseases (epidermolysis bullosa), Dermatology in General Medicine. First edition. Edited by TB Fitzpatrick. New York, McGraw-Hill Book Company, 1971, pp 621.643
3. Cockayne EA: Recurrent bullous eruption of the feet. Br J Dermatol 50:358-362, 1938 4. Herlitz G: ,Kongenitaler, nicht sypbilitischer Pemphigus. Eine Ubersicht nebst Beschreiburgeiner neuen Krankheitsform. Acta Paediatr 17:315-317, 1935
5. Pearson RW: The mechanobullous diseases (epidermolysis bullosa), Dermatology in General
Dermolytic Bullous Dermatosis
. . . LoVerme and Oropollo
401
Medicine. First edition. Edited by Tl3 Fitzpatrick. New York, McGraw-Hill Book Company, 1971, pp 635-639
10. Marshall RF: A comment on epidermolysis bullosa and its anesthetic management for dental operations. Br J Anaesth 35: 724-727, 1965
6. Crikelair GF, Hoehn FU, Domonkos AN, et al: Skin homografts in epidermolysis bullosa dystrophica. Plast Reconstr Surg 46:89-92, 1970
11. Pers M: Skin grafting in a case of epidermolysis bullosa. Acta Chir Scand 129:333-334, 1965
7. Rees TD, Swinyard CA: Rehabilitative digital surgery in epidermolysis bullosa. Plast Reconstr Surg 40: 169-174, 1967
8. Lee C, Nagel EL: Anesthetic management of a patient with recessive epidermolysis bullosa dystrophica. Anesthesiology 43: 122-124, 1975 9. Kubota Y, Norton ML, Goldenberg S, et al: Anesthetic management of patients with epidermolysis bullosa undergoing surgery. Anesth Analg 40:244-250, 1961
12. Wilson F: Epidermolysis bullosa: a rare disease of anaesthetic interest. Br J Anaesth 31: 26-31, 1959 13. Young DA, Hardwick PB: Anaesthesia for epidermolysis bullosa dystrophica. Anaesthesia 23: 264-267, 1968 14. Petty WC, Gunther RC: Anesthesia for nonfacial surgery in polydysplastic epidermolysis bullosa (dystrophic). Anesth Analg 49: 246-250, 1970 15. Corssen G, Gutierrez J, Reves JG, et al: Ketamine in the anesthetic management of asthmatic patients. Anesth Analg 51:588-596, 1972
VENTILATORY FAILURE. A n obese (52.9 k g ) 10-year-old boy manifested unexplained respiratory failure associated with almost complete absence of hypoxic and hypercapnic ventilatory responses. Weight loss to 38.2 k g did not a l t e r t h e responses to either hypoxia or hypercapnia. Neurologic examination, including normal ninthcranial nerve function illustrated by intact gag reflex and heart-rate slowing during carotid-sinus massage, w a s negative. Thyroid function tests were normal. Ventilatory responses to both hypoxia and hypercapnia were found t o be depressed in both parents and 4 siblings. It seems t h a t genetically determined reductions in chemical stimulation to ventilation are the most likely explanations f o r this patient’s ventilatory failure. (Moore GC, Zioillich CW, Battaglia JD, et al: Respiratory failiirc associated with familial depression of ventilatory response to hypoxia and hypcreapnia. N E J M 295: 861-865,1976)
