4.2 Management of UAE event
Whenever it is suspected, the therapy of UAE should be started as early after recognition of onset of initial symptoms as possible. Edema of the face, lips, and neck require immediate intervention. Current options for pharmacotherapy in this treatment setting include plasma-derived C1-INH replacement therapy (pdC1-INH), icatibant (a bradykinin receptor antagonist), and ecallantide (a kallikrein inhibitor). More than 30 years of clinical experience exists using pdC1-INH. Intravenous administration of this agent in a 500 to 1000 U dose is followed by substantial improvement of clinical symptoms within 30 to 60 minutes. In the vast majority of cases, treatment with pdC1-INH usually eliminates symptoms completely within 12 hours [
9,
12,
15,
26‐
29]. Double blind, placebo-controlled studies conducted recently with pdC1-INH concentrate established its recommended dose at 20 U/kg. PdC1-INH concentrate is safe and effective with minimal side effects.. The viral safety of preparations manufactured using innovative pasteurization and nanofiltration technologies is excellent [
30]. Treatment with pdC1-INH concentrate does not lead to the formation of antibodies [
31] and is safe for children, pregnant women, and nursing mothers [
28]. Only limited data are available on its use in HAE-Type III-XII but appears effective in the majority of patients [
7]. In our opinion, the best approach is to dispense pdC1-INH concentrate directly to the patients so it is constantly available at home for use on demand. All patients followed up at the Hungarian Center have been provided with pdC1-INH concentrate free of charge. On proposal from the principal of the Center, family practitioners and specialists are authorized to prescribe this medicinal product in the outpatient care setting. Self-administration of emergency medication has substantially improved the patients' quality of life in some countries. Having mastered the technique of intravenous injection, patients may self-administer the drug or have it infused by an appropriate helper. Experience with the self-administration of pdC1-INH concentrate for the treatment of attacks suggests that it is a viable and safe option resulting in faster and more effective treatment of severe angioedema attacks in patients with HAE [
32‐
34].
The effectiveness and safety of the newer agents, icatibant and ecallantide have been demonstrated by clinical studies. Both are to be given by subcutaneous injection, which affords rapid and straightforward administration [
35,
36]. Experience from long-term follow-up is not yet available, as well as neither of these products has been approved for use in pregnant women, nursing mothers, pediatric patients, nor for self-administration. Notwithstanding this, there is huge demand among patients and doctors alike for additional, safe and effective therapeutic alternatives for HAE attacks and UAE in particular. Although it is not yet available for clinical use, recombinant C1-INH is a new drug for treatment as well [
37,
38]. If none of the approved medicinal products is available, fresh frozen or solvent-detergent plasma may be used. However, this is no longer considered state-of-the-art therapy and it may even worsen symptoms [
39]. Following the successful emergency therapy of UAE, medical observation of the patient is necessary in a facility where intensive care management is available until the complete resolution of symptoms.
If alarming signs of airway obstruction (such as stridor, dyspnea, and signs of respiratory arrest) occur, airway patency should be re-established and oxygen should be administered along with parenteral fluid replacement. Oro-or nasopharyngeal intubation may be useful in unconscious patients. If intubation is not deemed necessary, the patient should be placed in the semi-prone position, head down ('coma') position. If stridor, hoarseness or hypoxaemia are present, immediate intubation is essential,. The extent and localization of the edema may interfere with endotracheal intubation requiring airway patency be restored by surgical intervention.
Cricothyroidotomy is an emergency procedure to prevent death from suffocation caused by upper airway obstruction, when neither endotracheal intubation, nor tracheotomy is feasible. It is relatively easy to perform (the cricothyroid membrane is near to the skin surface) and is only infrequently associated with complications (such as subglottic stenosis, thyroid fracture, haemorrhage and pneumothorax). Commercial cricothyroidotomy sets are available. Inserting a large-bore intravenous catheter through the punctured cricothyroid membrane is a quick, simple, relatively safe and highly effective method. The minimum inner diameter of the tube allowing adequate gas exchange during spontaneous breathing is 3 millimeters.
Percutaneous tracheostomy (PCT) techniques are gaining increasing popularity in surgical ICU wards, especially in 'post-op' rooms or post-anesthesia care units. The indications for PCT are the same as those for standard tracheostomy.
Proper surgical tracheostomy under local anaesthesia may be a prudent approach under controlled conditions. When performing this procedure is not feasible owing to extreme edematous swelling of the neck, cricothyroidectomy is still available for re-establishing airway patency. In 10% of patients, the medical history contains emergency tracheotomy having been performed, occasionally on multiple occasions, before the diagnosis of HAE-C1-INH [
9]. Even more astonishingly, fear from the lack of appropriate emergency therapy has prompted some patients to opt for a permanent tracheostomy. In our patient population, previous tracheostomy was identified in the history of 7 of the 132 patients - 2 of them underwent this procedure twice and another 4 on four occasions. In 35 patients with HAE-Type III-FXII 74 episodes of laryngeal edema occured, 3 of these requiring intubation and in 1 case an emergency tracheotomy had to be perfomed [
7].