C1 esterase inhibitor deficiency may be either hereditary (hereditary angioneurotic oedema) or acquired in nature. It is a dominant autosomal disorder characterized by either decreased esterase inhibitor concentrations (Type I) or a faulty protein with normal levels (Type II). Acquired angioedema results from either increased C1 esterase inhibitor consumption associated with lymphoproliferative conditions or connective tissue involvement (Type I), or altered autoimmune pathways (Type II) [1,2]. Both hereditary and acquired angioedema are a major concern for the anaesthetist because patients with these pre-existing conditions may develop relapsing massive oedema involving the airway, notably the oral cavity, pharynx and larynx [1,3]. We report the perioperative management of a patient who presented with acquired angioneurotic oedema.
A 46-yr-old female (65 kg in weight and 160 cm in height) was scheduled for intraoperative biopsy plus elective mastectomy for a nodule located at the external upper quadrant of the right breast. History revealed contact eczema caused by nickel, chromium and cobalt, and infantile poliomyelitis that had given rise to a residual paralysis of the upper right limb. In the few previous months, the patient had had several episodes of face, lip and eyelid swelling, and had been diagnosed as having acquired angioneurotic oedema (decreased C1 INH, C1q, C2 and C4 levels). She had been prescribed danazol as a prophylactic treatment.
Full blood count, coagulation, blood biochemistry and chest X-ray were normal. Electrocardiogram (ECG) showed sinus rhythm with left anterior hemiblock. Premedication consisted of 1 mg oral lorazepam the night before surgery. On the morning of surgery, two units of fresh frozen plasma were prepared and the patient was administered 200 mg of danazol orally. Preparation was made in case of a difficult intubation. ECG, non-invasive blood pressure monitor, pulse oximeter and capnograph were connected. Induction of anaesthesia was performed with propofol and the trachea intubated. Anaesthesia was maintained using oxygen (O2)/nitrous oxide (N2O), isoflurane, fentanyl and vecuronium. The patient remained haemodynamically stable throughout the procedure and there was no significant bleeding. On completion of surgery, she was awoken and extubated. However, a few minutes later, the patient developed respiratory distress, stridor, increased mucus secretion, facial and upper limb swelling and O2 saturation fell to 72%. An otorhinolaryngologist was called and 100% O2 administered by mask. Two units of fresh frozen plasma were given. Within 35 min this worrying clinical picture had subsided, the patient was responding to verbal commands and O2 saturation had returned to 99%, facial and upper limb swellings persisted. The patient was transferred to the postanaesthesia recovery unit. Four hours later, she was symptom-free and facial and upper limb swellings had subsided.
Two years after the first operation, an osteolytic lesion involving the proximal end of the right femur was found in a routine surveillance visit at the Department of Oncology of our hospital, thereby the patient was scheduled for biopsy and prophylactic screw-plate osteosynthesis. Subarachnoid anaesthesia was administered uneventfully.
Hereditary angioneurotic oedema is a rare condition (incidence 1: 50 000-1: 500 000). It is most often seen during childhood and adolescence and other members of the family are affected. Acquired angioneurotic oedema is probably less frequent than the hereditary type, appearing later in life and without a family history. The incidence of acquired angioneurotic oedema is unknown and it may be associated with lymphoproliferative diseases or lupus erythematous .
C4 concentration screening can readily provide the differential diagnosis for forms of angioedema. Normal levels during an acute episode of angioedema rules out the diagnosis of C1 inhibitor deficiency, whereas decreased levels arouse suspicion of this enzyme deficiency. Patients with the acquired type have decreased C4, C2, C1 inhibitor and C1q levels, as well as C3 deficiency in Type II. Patients with the hereditary type may have either decreased or normal C1 inhibitor concentrations along with decreased C2 and C4 levels, and C1q levels within the normal range [1,4].
Treatment for C1 inhibitor deficiencies include androgens, antifibrinolytic drugs, fresh frozen plasma and C1 inhibitor concentrate. Prophylactic treatment is aimed at preventing airway obstruction in those patients who suffer from episodes of angioedema more frequently than once or twice a month. Favoured drugs for long-term treatment are danazol (600 mg day−1) and stanozolol (2 mg day−1) orally [1,2]. ε-aminocaproic acid, tranexamic acid and aprotinin are antifibrinolytic drugs which inhibit plasminogen and plasmin activation; therefore, they are candidate drugs for prophylactic treatment of angioedema episodes. Fresh frozen plasma contains C1 inhibitor but also kinins and substrates that play a role in complement activation and may result in hepatitis virus and human immunodeficiency virus transmission. While fresh frozen plasma is at times used preoperatively as well as for treatment of acute angioedema, it is advisable to reserve it for those cases in which purified C1 inhibitor is not available, as was the case in our patient . C1 inhibitor concentrate is the treatment of choice for acute angioedema episodes, resulting in partial remission of symptoms within 16-60 min and full remission within 24 h of administration. Furthermore, its protective action may last as long as 2 days. While C1 inhibitor has been used as a prophylactic treatment in patients with poor response to other therapeutic modalities, its routine usage is not because of the associated hazard of virus transmission. The common initial dose is 1000-2000 U; however, it should be borne in mind that patients with acquired angioneurotic oedema usually need higher doses because of increased C1 inhibitor consumption [2,4,5]. Preoperative diagnosis of hereditary or acquired angioedema is crucial for adequate perioperative management. Alonso and Fas have recently published a list of guidelines for perioperative management of these patients .
In these patients, the anaesthesiologist should be ready to manage the airway electively, when the airway is not compromised, urgently when mild to moderate airway oedema is present or in an emergency when airway swelling is life-threatening to the patient. Generally, oedema develops slowly, but at times it may develop within minutes with catastrophic consequences. The clinical presentation is similar in all types and includes a fullness in the mouth, dysphagia, facial tightness, hoarseness, dysphonia, stridor and laryngeal oedema or laryngospasm. Laryngoscopy for intubation may worsen laryngeal oedema, in which case emergency tracheotomy is needed . The role of the laryngeal mask is not established, although it seems likely that its use may worsen airway oedema [1,2].
Premedication with anxiolytic drugs is of paramount importance in these patients because preoperative stress may trigger an acute episode of oedema. Both general and subarachnoid anaesthesia have been used [2,6,7]. The presence of angioedema should not be a consideration in choosing induction agent or muscle relaxant. Succinylcholine appears to be safe . There are no articles in the literature addressing the use of volatile anaesthetic agents. Some authors advocate considering local and regional anaesthesia in patients with oedema in order to avoid orotracheal intubation [1,8].
For postoperative care, transfer to a high-dependency unit after surgery is advisable and airway oedema should be carefully monitored all the time. The decision to transfer the patient to the intensive care unit should be governed by the patient's general health, co-morbidities, complexity of the surgical procedure performed and complications, including those resulting from airway oedema . The postoperative episode of respiratory distress in our patients was likely to be due to airway oedema resulting from airway manipulation during extubation. There was a good response to fresh frozen plasma replacement therapy.
García J. C. Collada
Pereda R. M. Marín
Miralles E. M. Serrano
Garrote A. I. Martínez
Pacheco J. F. López
*Department of Anaesthesiology, Virgen de La Luz Hospital, Hermandad Donantes de Sangre Cuenca, Spain
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