Case Report
Acute Cardiac Failure after Muscle Block Reversal with Sugammadex for Unexpected Difficult Intubation
*Carmelina Gurrieri, *Paolo Murabito *Giovanni Buscema, *, Danilo Grasso, *Marinella Astuto
- Submitted: Sunday, March 02, 2014
- Accepted: ; Saturday, March 15, 2014
- Published: Sunday, April 06, 2014
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Abstract
We report a case of a 12 year old girl who developed a life threatening reaction after muscle block reversal with sugammadex for unexpected difficult intubation. She experienced severe signs of bronchospasm, decreased oxygen saturation, difficulty in ventilation and cardiovascular failure. She required inotropic support, emergency tracheostomy and ICU admission.
Keywords
sugammadex, difficult intubation, allergic reaction, pediatric anesthesia
Case report
A 12 year old girl (height 140 cm, weight 40 kg) underwent general anesthesia for left eye retinal detachment. She has previously had multiple ophthalmology surgeries under general anesthesia. All the procedures were uneventful, except for a single cutaneous reaction after intravenous (iv) administration of doxycycline. The last surgery was performed at our institution one month previously without any problem; neither difficulty in ventilation nor intubation were reported. Tests were running for suspected Marfan syndrome. Her parents referred different episodes of inspiratory stridor in childhood that resolved spontaneously and one episode of chest pain and dyspnea following a cold and requiring hospitalization six months before. At that time neither cardiac nor respiratory failure occurred. The day of surgery, anesthesia was started with sevoflurane 8% in 50% O2/Air. After positioning a peripheral line access with an 18G catheter, anesthesia was induced with 100 mg of propofol, 20 mg of rocuronium and continuous infusion of remifentanil hydrochloride at 0.30 mcg/kg/min. [1] A Cormack 3 was visualized after laryngoscopy with a size 3 curved blade laryngoscope and a first attempt of intubation failed. An emergency airway cart was available in the operating room. A senior anesthesiologist was called. [2] The patient was ventilated with a size 3 facial mask and oxygen saturation was maintained over 97%. A second attempt of intubation was performed but it failed. At this time it was decided to proceed with the administration of 160 mg of sugammadex (4 mg/Kg) for muscle blocker reversal. The patient started to breath spontaneously with a TOF (train of four) ratio of 87%. Three minutes later oxygen saturation initiated to decrease and ventilation became difficult. At this point it was decided to perform an awake intubation using a fiberscope. The patient was successfully intubated with a size 6 oral endotracheal tube. However, she suddenly showed signs of airway distress with high-pitched respiratory sounds, external paradoxical respiration and abundant foamy pink secretions. Oxygen saturation decreased to 75% on 100% O2, blood pressure dropped to 60/40 and a severe bradycardia occurred. An anaphylactic reaction was suspected; therefore, 0.4 mg (10 mcg/Kg) epinephrine iv, 100 mg (2.5 mg/Kg) hydrocortisone iv, 40 mg diphenhydramine iv were administered. Moreover, a bolus of 500 ml of fluids was injected. Patient’s clinical conditions did not improve significantly. At this time, epinephrine infusion was started at the dosage of 0.1 mcg/Kg/min and an emergency percutaneous tracheostomy was performed with a size 7.5 cannula because the abundant secretions made the patient difficult to ventilate. Once stabilized, the girl was transferred to the ICU for intensive care monitoring and assistance. Echocardiography found a severe systolic dysfunction with an ejection fraction of 35%, a moderate mitral valve prolapse with mild insufficiency and signs of previous pericarditis. A bronchoscopy showed the presence of subglottic granulations and glottis edema. Patient’s clinical conditions improved over the next few days. She was progressively weaned from epinephrine support and from mechanical ventilation. During the ICU staying neither cardiac or respiratory compromising occurred. Ten days later the patient was transferred to the pediatric ward where she was followed up. No other major complications occurred.
Discussion
We describe a life threatening reaction that occurred under general anesthesia in a 12 year old girl with suspected Marfan syndrome. Our first suspicion was an allergic reaction to sugammadex. This hypothesis was supported by different reasons. First of all, the timeframe of the reaction which occurred shortly after the administration of the drug. We excluded that the reaction could be attributed to the other anesthetics because all of them but not sugammadex have been administered in the previous anesthesia. The patient, in fact, was firstly administered sugammadex at the time of the reaction, although prior sensitization to other drugs, or to common operating room environmental substances, could result in similar adverse reactions due to cross-sensitivity. [3] Secondly, clinical manifestations of the event consisting of a rapid, acute cardiovascular collapse and respiratory failure, which are the most common clinical features of peri operative allergic reactions. [4] As it is known anaphylactic reactions during anesthesia are rare but potentially fatal events [5,7] mostly related to antibiotics, muscle blockers and latex. [6,9] The initial diagnosis of a peri-operative anaphylactic reaction is based primarily on clinical evaluation [10] and then confirmed by serologic and skin tests. Tryptase level evaluation, for example, may trigger an immune-mediated allergic event, [11,12] although a negative value may not exclude an anaphylactic reaction. [12,13] At our institution, unfortunately, tryptase test is not available yet and allergy evaluation consisted of a detailed clinical history, skin prick and intradermal tests. In our case, however, we could not perform any allergy tests due to the lack of the parents’ consent. Thus, we can speculate that previous exposure to cyclodextrins, substances present in many foods, drugs and cosmetics, might have sensitized our patient. [3] It has been reported that a human ingests approximately 4 g of cyclodextrins per day [3,14]. Moreover, the combination of sensitization to cyclodextrins in a patient with a previous allergic reaction to doxycycline may have triggered the event.
In the literature there are still few reports of allergic reactions to sugammadex, a relatively new muscle blocker reversal drug, selective for rocorunium. [15] Sugammadex is usually a well-tolerated drug, [16] but some studies [17,18] have reported only mild allergic reactions to its administration at high doses (16 mg/Kg). Erythema, flushing, headache, nausea, dry mouth, cold feeling and irritation at the site of injection, are the most common clinical manifestations, usually not required treatment. There are also reports regarding sugammadex use in the treatment of anaphylaxis to rocuronium. [19,20] McDonnell et al. [19] for example, described a temporally marked improvement of patient’ critical conditions related to a severe allergic reaction to rocuronium after the administration of sugammadex at the dosage of 6.5 mg/Kg. However, in the last few years some cases of sugammadex-related allergic reactions at low dose have been appearing in the literature. [3,21,22] Mene´ndez-Ozcoidi et al. [3] reported an allergic reaction to 3.2 mg/Kg sugammadex in a 17 year old boy. Clinical manifestations were severe erythema, desaturation and decreased blood pressure. The allergy was confirmed by a skin prick test. This was one of the first confirmed allergy to the drug. Asahi et al. [21] used a very similar dosage (3.3 mg/Kg) for a 7 year old boy with cerebral palsy. The allergy could not be confirmed, like our case and the suspicion was related to the timeframe of the drug administration and clinical manifestations of the reaction. An even lower dosage (2.3 mg/Kg) was reported by Soria et al. [22] in an adult patient undergoing laryngoscopy for a suspected vocal cord tumor. More recently, other cases of allergic reactions to sugammadex have been reported. [23,24] All were confirmed by intradermal skin tests and elevated tryptase level which, however, remained normal in one patient. These articles highlight not only the risk of anaphylactic reactions after the administration of sugammadex, but also the difficulties in establishing the diagnosis, as there are still no standardized dilutions of skin testing for hypersensitivity to sugammadex. [24] As consequence, there could be false positive results on skin testing. Moreover, the mechanism of sugammadex-induced allergic reaction remains not well known and the interaction between the drug and rocoronium needs further assessment. [25]
As already mentioned, in our case unfortunately, the allergy could not be confirmed neither by serologic or skin tests, thus another explanation for the event should be taken in consideration. Our second suspicion was pulmonary edema. In fact, based upon patient’s clinical manifestations (difficulty in ventilation, bronchospasm, desaturation and abundant foamy pink secretions) and on the echocardiography signs (acute left ventricle failure) we could speculate on pulmonary edema as another possible route. Our case could be a non cardiogenic pulmonary edema caused by bronchospasm, also noted as post-obstructive pulmonary edema. It is usually unrecognized and rarely reported in the setting of a bronchospasm, with an incidence from 0.05 to 0.1% of all anesthetics. [26] The first report in literature was in 1977 by Oswalt CE et al. [27] They described three cases of pulmonary edema induced by a severe negative pressure following upper airway obstruction. Other cases have been reported, both in adults and in children. [28,31] More recently the report of Krodel et al. [32] described a case of bronchospasm-related pulmonary edema in a 43 year old woman with severe asthma and chronic obstructive pulmonary disease (COPD) scheduled for cervicectomy. The exact mechanism by which upper airway obstruction may precipitate pulmonary edema is not known with certainty. Predisposing factors might be pre-existing pulmonary pathologies such as asthma and COPD which can cause significant airway narrowing, airway edema and subsequent bronchocostriction. The predominant mechanism appears to be the transmission of marked negative intrapleural pressures in the pulmonary capillary bed, which lead to an increase of venous return of blood to the heart, increased left ventricle stress and, consequently, to a rapid fluid accumulation in the lungs. [27]
Conclusion
We report a case of a life threatening condition that occurred after the administration of sugammadex for muscle blocker reversal. It might be an allergic reaction to sugammadex administered at the dosage of 4mg/Kg. Although we are not able to confirm our suspicion and to exclude other causes such as pulmonary edema, the timeframe of the reaction and clinical manifestations suggest a possible allergic reaction. Sugammadex is still a useful and well-tolerated drug, however, clinicians should take into consideration that allergic reactions may occur after its administration.
Learning points
-Sugammadex is a very effective drug that provide a rapid reversal of rocoronium-induced residual neuromuscular blockade
-Sugammadex is a generally safe and well tolerated drug, however it may cause potentially fatal allergic reactions
- The immunological mechanism of sugammadex induced anaphylactic reaction and the interaction of the drug with rocuronium need further assessment
The authors declare no conflicts of interest
Authors' Contribution
CG conceived the study, participated in design, edited the
final manuscript.
PM carried out the literature search and prepared the draft
manuscript.
GB carried out the literature search and interpreted the results.
DG carried out the literature search and prepared the draft manuscript.
MA
conceived and designed the study, and edited the final manuscript.
All
authors have read and approved the final manuscript for submission.
Conflict of Interests
The authors declare that their are no conflicts of interests.
Ethical Considerations
Written informed consent was obtained from the patient for
publication of this report.
Funding
None
Acknowledgements
None
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