Case report: Intraoperative anaphylactoid reaction and hydroxyethyl starch in balanced electrolyte solution (Hextend®)

Brian A. Hall Evangelo Frigas Damir Matesic Michael D. Gillett Juraj Sprung [Prsentation de cas : raction anaphylactode peropratoire et amidon hydroxythyl dans une solution d'lectrolyte balance (Hextend)] Purpose: To report a first case of probable anaphylactoid reaction to 6% hydroxyethyl starch reconstituted in balanced electrolyte and glucose solution (Hextend). Clinical features: A 22-yr-old man was admitted for a partial nephrectomy. Near the end of the four-hour operation, an infusion of Hextend was initiated. Shortly thereafter, mechanical ventilation became difficult, peak inspiratory pressure increased to 55 cm H2O with audible wheezing over the patient's lungs. Blood pressure suddenly decreased to 68/46 mmHg. Multiple doses of phenylephrine, ephedrine and epinephrine were required to restore the patient's blood pressure. Postoperatively, a diffuse urticarial rash was apparent on his upper torso. The patient recovered uneventfully. His postoperative serum tryptase was 26.3 ngmL-1 (reference range, < 11.5 ngmL-1) and the urine N-methyl-histamine was 2448 gg-1 creatinine (reference range, 30-200 gg-1 creatinine). Two months after the event, skin testing was conducted to test for possible allergy to latex, lidocaine, propofol, cisatracurium, succinylcholine, vecuronium, midazolam, fentanyl, ondansetron, neostigmine, and cephazolin, and all were negative. Hextend was also tested, starting with a 1:100,000 dilution and the results were negative. Conclusions: The temporal relationship of severe hypotension, bronchospasm and skin rash within ten minutes from administration of Hextend in this patient suggests an immediate hypersensitivity reaction to hetastarch. The elevated levels of serum tryptase and urinary N-methyl-histamine suggest that this hypersensitivity was mediated from mast cell degranulation. Negative skin testing suggests that the reaction was anaphylactoid. - lments cliniques : Un homme de 22 ans a t admis pour une nphrectomie partielle. Vers la fin de lopration de quatre heures, une perfusion dHextend a t amorce. Peu aprs, la ventilation mcanique est devenue difficile, la pression inspiratoire maximale est monte 55 cm H2O et saccompagnait de sifflement perceptible lauscultation des poumons. La tension artrielle a soudainement chut 68/46 mmHg. De multiples doses de phnylphrine, dphdrine et dpinphrine ont t ncessaires pour restaurer la tension artrielle du patient. Aprs lopration, une ruption urticarienne tait apparente la partie suprieure du torse. Une rcupration sans incident a suivi. La tryptase srique postopratoire a t de 26,3 ngmL-1 (tendue de rfrence, < 11.5 ngmL-1) et la N-mthyl-histamine urinaire a t de 2448 gg-1 de cratinine (tendue de rfrence, 30200 gg-1 de cratinine). Deux mois aprs lvnement, des tests dallergie cutane au latex, la lidocane, au propofol, au cisatracurium, la succinylcholine, au vcuronium, au midazolam, au fentanyl, londanstron, la nostigmine et la cphazoline ont t mens et se sont tous rvls ngatifs. Le Hextend a t aussi test, en commenant avec une dilution 1:100 000 et les rsultats ont t ngatifs. Conclusion : La relation temporelle entre lhypotension svre, le bronchospasme et lruption cutane en moins de dix minutes aprs ladministration du Hextend laisse croire une raction dhypersensibilit immdiate lhtamidon. Les niveaux levs de tryptase srique et de N-mthyl-histamine urinaire indiquent que cette hypersensibilit origine dune dgranulation des basophiles. Les tests cutans ngatifs montrent que la raction tait anaphylactode. Hconsists of hydroxyethylated polymers of YDROXYETHYL starch (HES), a synthetic colloid derived from amylopectin, glucose. The physical characteristics of hydroxyethyl starch can be described by their average molecular weight (MW) and their molar substitution ratio (i.e., the ratio of replacement of glucose by hydroxyethyl group). For example, hetastarch has an average MW of 450 kDa with a molar substitution of 0.7, therefore it is labelled 450/0.7. Pentastarch, labelled as 200/0.5, is a low MW (average 200 kDa) product with a lower molar substitution (0.5). Hespan (Hospira, Inc., Lake Forest, IL, USA; 6% hetastarch in 0.9% sodium chloride) has an average MW 600 kDa, and molar substitution of approximately 0.75 (600/0.75). Hextend (BioTime, Inc., Berkeley, CA, USA), is a high MW (average 670 kDa) 6% hydroxyethyl starch, reconstituted in balanced electrolyte and glucose solution, with molar substitution ratio of 0.75, and is labelled 670/0.75.1,2 Due to their established efficacy in replenishing intravascular volume, HES solutions are widely used to treat hypovolemia. However, their use is not free from the risk of allergic reactions,3 which is estimated to 0.0004%,4 and the risk of life-threatening reactions is reported to be 0.006%.5 The clinical picture of allergic reactions to HES may range from skin manifestations to severe and life-threatening complications. While allergic reactions to lower MW hydroxyethyl starches have been reported,69 we present a patient who developed a severe intraoperative allergic reaction soon after initiation of high MW hetastarch, Hextend infusion. This patients high postoperative serum tryptase concentration initially suggested anaphylaxis, but subsequent skin testing excluded an IgE-mediated mechanism and suggested an anaphylactoid reaction. Case report With the approval of the Mayo Clinic Institutional Review Board Ethics Committee, a retrospective review of our patients medical records was conducted. A 22-yr-old, 65-kg male, was admitted for partial nephrectomy due to hydronephrosis of the upper pole of his right kidney secondary to duplication of the right kidney urinary collection system. His medical history was significant for mild hypertension and asthma. His only home medication was albuterol, used occasionally for chest tightness, which he had not required before surgery. He reported codeine as his only allergy. He had no prior surgical history. The patients pre-induction blood pressure and heart rate were 114/56 mmHg and 67 beatsmin1 respectively. A 16-G peripheral iv line was placed prior to an uneventful induction which was achieved with fentanyl, midazolam, propofol and lidocaine. Tracheal intubation was facilitated with a defasciculating dose of vecuronium 0.7 mg iv followed by succinylcholine 120 mg iv. Immediately after induction of anesthesia, cephazolin 1000 mg iv was administered uneventfully. Following induction, anesthesia was maintained with isoflurane and the patients lungs were ventilated to eucarbia with 50% oxygen mixed with air. A 14-G peripheral iv line was inserted, as well as a left 20-G arterial radial catheter. The blood pressure following induction was 120/75 mmHg, and heart rate was 85 beatsmin1. The patients hemodynamic course remained stable throughout the first three hours of the procedure, during which cisatracurium and incremental doses of oxymorphone were administered as required to maintain muscle relaxation and analges (...truncated)