1Department of Anaesthesia, 2Radiology Department, 3Vascular Surgical Unit, University College London Hospitals, Mortimer Street, London W1N 8AA, UK*Corresponding author: Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
Accepted for publication: August 28, 2001
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Abstract |
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Br J Anaesth 2002; 88: 1335
Keywords: arteries, abdominal aortic aneurysm; complications, anaphylaxis; surgery, aneurysm
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Introduction |
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Case report |
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On the day of admission the patient had aortography to define the precise position of the aortic stent; 100 ml contrast solution (Omnipaque) was used.
For the endovascular procedure the next day, anaesthesia was induced with fentanyl 100 µg, propofol 140 mg and atracurium 50 mg, and maintained with isoflurane (inspired concentration 0.81.2 vol%) and nitrous oxide in oxygen (nitrous oxide >50%/oxygen >30%). The right radial artery and right internal jugular vein were cannulated for continuous monitoring of arterial pressure and right atrial pressure and the patient was transferred to the operating theatre. Surgery proceeded uneventfully for 2 h. There was no administration of additional drugs, colloid or blood during this period. For maintenance therapy, 0.9% sodium chloride 5 ml kg1 h1 was given.
Immediately before the attachment of the endoluminal stent to the aortic wall, 250 ml radiopaque contrast (Omnipaque) was injected via the right femoral artery to determine that it was positioned correctly. Shortly afterwards, the deployment of the graft with expansion of the balloon was completed.
Five min after administration of the radiocontrast material, the arterial pressure decreased markedly. The systolic arterial pressure decreased progressively and reached 20 mm Hg despite administration of increments of ephedrine (30 mg in total), epinephrine 1 mg and crystalloids 1000 ml. The heart rate was 130 beat min1 but no cardiac output was detected. Indirect cardiac massage was started as electromechanical dissociation arrest was evident on ECG. Arterial blood gases at this time were: pH 7.4, PaCO2 4.77 kPa, PaO2 24.0 kPa, base excess 1.8 and SaO2 99.6% with FIO2 1.0. No bronchospasm, rash or periorbital oedema were observed.
Resuscitation continued for 20 min and comprised epinephrine 3 mg and norepinephrine 1 mg, four units of blood, crystalloids 2000 ml and colloids 1000 ml.
Within 30 min, the systolic arterial pressure stabilized at 7080 mm Hg with a continuous infusion of epinephrine 0.1 µg kg1 min1, and the decision not to convert to open surgery was taken. The procedure was completed successfully.
The patient was then admitted to the intensive care unit. An acute systemic reaction to RCM was suspected at that time. Blood was obtained for measurement of serum mast-cell tryptase concentration, routine blood tests and clotting screen. Hydrocortisone 100 mg i.v. was included in the treatment and continuous venovenous haemofiltration started.
The patients condition improved dramatically over the next few hours, and he was weaned off inotropic support. He was extubated the following morning and was discharged from hospital 4 days later with no side-effects. He was referred to an allergy clinic for further investigations and management.
Three hours after the reaction, the serum mast-cell tryptase concentration was 31.4 ng ml1 (normal range 214 ng ml1). After consultation with the Supraregional Protein Reference Unit based in Sheffield, where the samples were analysed, the true value was estimated to be 60 ng ml1 as a result of the haemodilution effect of the resuscitating fluids. The next two samples, obtained 8 and 12 h after the incident, when the patient was on haemofiltration, showed serum tryptase concentrations of 25.6 ng ml1 and 25.5 ng ml1, respectively. These results were compatible with mast-cell degranulation. There was also a moderate derangement of the patients clotting profile: APTT 140 s (control 31.2), PT 23 s (control 12.9) and INR 1.83.
CT scan performed 5 days later showed no leak from the graft, with no free fluid in the retroperitoneal space, favouring the diagnosis of acute anaphylaxis as a cause of the cardiac arrest.
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Discussion |
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There are two groups of RCM: ionic, hyperosmolar (1500 mOsm kg1) or first-generation solutions, and the newer, second-generation, non-ionic, hypo- and iso-osmolar (350700 mOsm kg1) agents. It is widely accepted that the first-generation RCMs are more toxic and more immunogenic and therefore responsible for a higher morbidity, including allergic reactions.
There is emerging evidence,6 however, that some of the newer non-ionic hypo-osmolar RCMs can trigger a true anaphylactic reaction, directly activating IgE antibodies. Iopamidol and ioversol, for example, have chemical structures that resemble the mirror molecules of succinylcholine and other neuromuscular blocking agents. They have two identical side-chains containing quaternary ammonium groups which can cross-link to IgE molecules. In theory, these new RCM could be more immunogenic than the older first-generation ionic hyperosmolar solutions, but there are insufficient data to confirm this. However, new preparations have significantly lower overall toxicity and fewer side-effects.
In 1970, Ansell reported life-threatening reactions to the first-generation ionic contrast agents in 0.010.02% of all radiological examinations7 but more recently the incidence of a fatal outcome has been reported in only 1 in 40 000 administrations.8 In 1992, Lieberman reported an incidence of severe, but not necessarily fatal, anaphylactoid reactions in 12% of all contrast studies,9 perhaps attributable to the growing number of radiological investigations and previous under-reporting of adverse reactions. With the introduction of the new generation of non-ionic, low-osmolar RCM, this risk has been reduced 510 fold.4 8
Iohexol (Omnipaque) is another new, second-generation RCM. It is the most frequently used x-ray contrast medium for arteriography, cardioangiography, urography, hysterosalpingography, gastrointestinal tract and CT investigations. It is a non-ionic, monomeric, tri-iodinated, water-soluble, isotonic solution containing iohexol 140350 mg ml1. It is almost 100% excreted unchanged through the kidneys within 24 h of administration. It is less than 2% protein bound and has no detectable metabolites.
Our patient had an acute anaphylactic reaction to contrast medium under general anaesthesia and during a major surgical intervention. The reaction occurred in typical fashion, 35 min after administration of the contrast medium and followed re-exposure to the allergen (RCM).10 The lack of other signs of an acute allergic reaction (e.g. bronchospasm, histamine release) made the recognition of anaphylactic shock very difficult. Furthermore, the time of the reaction coincided with surgical manipulation of the aorta, when aortic rupture is particularly difficult to exclude. Unchanged haemoglobin concentration, lack of abdominal distension and a good response to high doses of epinephrine did not support the diagnosis of vessel rupture. Although we did not suspect an anaphylactic reaction immediately, we ruled out massive blood loss in the operating theatre, and the surgery was completed successfully.
Tryptase is a neutral protease concentrated in the secretory granules of mast cells. It serves as a specific marker for mast-cell activation and its concentration is linearly related to histamine release.11 We accepted the 5-times-normal-range tryptase concentration as proof of our clinical diagnosis.12 (Concentrations above 20 ng ml1 are considered indicative of an anaphylactoid or anaphylactic reaction.)
This patient had end-stage renal failure but we followed the renal physicians recommendation not to haemodialyse before the operation. It is unlikely that haemodialysis before surgery would have influenced the severity of the reaction because the patient was already sensitized to RCM during the previous radiological examination (diagnostic angiography). However, we feel that haemofiltration in the immediate postoperative period contributed considerably to the speed of recovery because of the more rapid elimination of inflammatory mediators.13
We believe that this is the first case of anaphylactic shock reported in a patient undergoing EAAA, a technique which is increasingly being used. It is important to draw the attention of anaesthetists to the potential allergenicity of RCM, in particular when contrast solutions are used during surgery. In the case of an acute anaphylactic reaction, prompt recognition and early and continuous treatment remain important for a successful outcome.
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References |
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