Case Reports

Timing of Sugammadex administration: a case report

AmitFrenkel1, Aviel Roy-Shapira1,3, Alexander Zlotnik2, EvgeniBrotfain1,

Leonid Koyfman1,  Yoav Bichovsky2, Moti Klein1

1General Intensive Care Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, (Israel)

2Department of Anesthesiology, Soroka University Medical Center, Beer Sheva, (Israel)

3Department of General Surgery, SorokaUniversity Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, (Israel)

Correspondence:Dr. Amit Frenkel, MD, MHA, General Intensive Care Unit,Soroka University Medical Center, Beer Sheva, (Israel); E-mail: frenkela@prognosa.co.il

ABSTRACT

Sugammadexis a relatively new drug used to reverse the effects ofrocuronium, a non-depolarizing muscle relaxing agenttohasten emergence from general anesthesia.  Unlike neostigmine and atropine, its use is not associated with re-curarization or cardiac arrhythmias. Sugammadex carries a small risk of allergic reactions including anaphylactic shock.

We present a case report of a 67 years old woman who underwent an urgent operation for small bowel obstruction. Due to atrial fibrillation (AF)the anesthesiologistadministeredSugammadex just before skin closure. Soonafter the injection, peak inspiratory pressures (PIP)increased precipitously followed by hypotension and increasing tachycardia.For anticipated cardioversion, the chest was exposed and it revealedurticarial.There was severe bronchospasm on auscultation. Treatment of anaphylactic shock was initiated, the patient improved dramatically and fully recovered.

This case is presented to alert practitioners to the importance of a sudden rise in PIP after Sugammadexadministration inthe early diagnosis of an anaphylactic reaction, and to suggest that due to the risk of anaphylaxis, it may be advisable to initiate sugammadexonly when the patient can be fully exposed without compromising the sterility of the operating field.

Key words: Muscle relaxant;Anaphylaxis; Allergic reactions

Citation: Frenkel A, Roy-Shapira A, Zlotnik A, Brotfain E, Koyfman L, Bichovsky Y, Klein M.  Timing of Sugammadex administration:  a case report. Anaesth Pain & Intensive Care 2015;19(2):163-65

INTRODUCTION

Sugammadex[Org 25969, trade name Bridion (Merck & Co., Inc.)]is relatively a new drug used for reversing skeletal muscle paralysis induced by steroidal neuromuscular blocking agentssuch as rocuronium and ‎vecuronium.1Unlike competitive reversing agents, sugammadex forms a complex with the paralytic moleculescirculating in the plasma, and enhances their elimination by the kidney. Consequently, it eliminates the risk of post-operative residual curarization associated with the traditional competitive reversing agents.  In randomized controlled trials sugammadex reliably shortened muscle relaxation from 20 to 1min.2

While sugammadex had been shown to be safe and effective reversing agent, it is associated with hypersensitivity reactions including anaphylactic shock in up to 1% of the cases.3Delayed suspicion and a delayed diagnosis can happen when the drug is given while the patient’s body cannot be exposed (for example, during skin closure) and urticaria cannot be observed.

The purpose of this presentation is to alert physicians to the importance of a sudden rise in peak inspiratory pressure (PIP) in the early diagnosis of anaphylaxis, in order to avoid premature extubation. The development of laryngeal edema may make re-intubation difficult or even impossible. A safer timing of sugammadex administration may be sought.

CASE REPORT

A67 year old woman, with a body mass index of 32, required an urgent laparotomy for small bowel obstruction. General anesthesia was induced with150 mg of propofol 1% and 150 µg of fentanyl. Rocuronium was used for muscle relaxation on induction.  Anesthesia was maintained withisoflurane, fentanyl 100 µgbolus and rocuronium20 mgbolus. Soon after induction she developed atrial fibrillation with rapid ventricular response, however, there was no hemodynamic compromise.Inj. amiodarone was used to slow down the ventricular rate from 120-140 beats per minute (bpm) to 90-100 bpm. The operation was uneventful and lasted for 30 min, after whichreversal of neuromuscular blockade was initiated.  Due to the arrhythmia, the anesthesiologist eschewed traditional reversing agent (neostigmine and atropine) in favor of sugammadex, in order to avoid exacerbation of the rapid ventricular response.

Two minutes after administration of sugammadex (200 mgIV)PIProse precipitously to 45cmH2O. The anesthesiologist suspected that the patient was struggling against the ventilator, and considered increasing the depth of anesthesia. However, blood pressure dropped to 70/40 mmHg and the ventricular rate rose to 140-160bpm. The rapid AF was interpreted asto be a result of “high adrenergic drive” on recovery from anesthesia, and the drop in blood pressure was attributed to low cardiac output secondary to the rapid heat rate. Consequently, it was decided to attempt cardioversion.

When the sterile sheets covering the chest were removed, erythema and urticaria of the chest wall was observed.PIP increased further, and on auscultation a decreased bilateral airflow accompanied by expiratory wheezewas noted.

At this point, a diagnosis of anaphylactic shock was made, and treated with 0.5 mg adrenaline, 200 mg hydrocortisone IV and 2 ml of intra-tracheal albuterol. The patient improved dramatically: airway resistance, as measured by PIP, normalized, blood pressure rose to 90/60 mmHg, and wheezing on auscultation became less severe. The patient was shifted to ICUand was extubated after 14 hours, without any further sequelae.

DISCUSSION

While the potential of sugammadex to cause anaphylactic shock is well known,4the presentation in our patient was unusual. Sugammadex was administered when the operation was still going on, but the muscle relaxation was no longer needed. Consequently the patient was still covered by sterile sheets, and observation of the skin was impossible.  The resulting delay in diagnosis could have been disastrous.

The temporal relationship between administration of sugammadex and the sudden rise in PIP could have alerted the anesthesiologist to the possibility of bronchospasm due to anaphylaxis, but the differential diagnosis is not straight forward and until the patient was exposed and the rash was observed, it was difficult to rule out other alternative explanations.

This case suggests that the timing of reversing neuromuscular blockade with sugammadex should differ from the timing of reversal with traditional agents. When using traditional reversing agents, it is customary to start them as soon as muscle relaxation is no longer required. The usual timing enables extubation immediately after skin closure, rapid turn over the patients and better utilization of resources. In addition, it allows longer observation against post-operative residual curarization.However, due to the risk of anaphylaxis, it seems unwise to follow the same practice with sugammadex.

This case indicates that it is probably safer to administersugammadex only after the skin is closed, and the covers can be removedwithout compromising the sterility of the field.  The short delay will allow unhindered observation of signs of an allergic reaction or anaphylaxis. Because sugammadex acts very quickly, and is free from residual curarization, waiting the extra minute or two should not materially affect operating room utilization or case turnover rate. In our case presented here, delaying reversal would have led to earlier diagnosis, and treatment could have been initiated before desaturation and collapse.

REFERENCES

1.  Nag K, Singh DR, Shetti AN, Kumar H, Sivashanmugam T, Parthasarathy S. Sugammadex: A revolutionary drug in neuromuscular pharmacology. Anesth Essays and Research 2013 Sep-Dec; 7(3):302-6.[PubMed][Free Full Text]

2. Takeda J, Iwasaki H, Otagiri T, Katoh T, Shingu K, Obara H, et al. Efficacy and safety of Sugammadex in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients.Masui 2014 Oct; 63(10):1083-8[PubMed]

3.Baldo BA.Sugammadex and hypersensitivity. Anaesth Intensive Care 2014 Jul; 42(4):525-7[PubMed]

4. Tsur A, Kalansky A. Hypersensitivity associated with Sugammadex administration: a systematic review. Anaesthesia 2014 Nov; 69(11):1251-7[PubMed]