Reporte de Caso

Sugammadex Use in a Patient with Chronic Renal Failure

Santiago Medina Ramírez*, Ana Milena Sánchez**, Francisco Gómez Oquendo***

* Residente de Anestesiología y Reanimación. Universidad de Antioquia. Medellín, Colombia.

** Anestesióloga Universidad de Antioquia. HUSVP. Medellín, Colombia.

*** Profesor titular y jefe de la sección de Anestesiología y Reanimación. Universidad de Antioquia. Medellín, Colombia. Correspondencia: Calle 64# 51 D-38 Medellin, Colombia. Correo electrónico: fajago@une.net.co

Recibido: diciembre 14 de 2010. Enviado para modificaciones: mayo 19 de 2011. Aceptado: junio 3 de 2011.

SUMMARY

The introduction of sugammadex in clinical practice could improve the safety profile of muscle relaxants, however, its use in patients with renal diseases is questionable when considering its clearance mechanism, as this could generate some problems. This case report describes a patient with renal disease in whom sugammadex was administered with a quick neuromuscular block reversal without any adverse effects.

Key Words: Neuromuscular Blocking Agents, Kidney Failure, Chronic, Intubation, Intratracheal, Laparoscopy. (Source: MeSH, NLM).

INTRODUCTION

Muscle relaxants are part of the pharmacological armamentarium available for anesthesia. These allow adequate oral tracheal intubation conditions, as well as appropriate conditions to the surgeons who require neuromuscular paralysis in procedures like laparoscopy.

Since their introduction, muscle relaxants have been associated with morbidity. Residual neuromuscular paralysis is one of the major concerns with their use, as the medications available for reversal (like the cholinesterase inhibitors) have their limitations not only because of their mechanism of action but also because of adverse effects (1).

These limitations, in addition to the nonexistence of an ideal muscle relaxant, generated in recent years a particular interest in developing new agents for neuromuscular block reversal that could be safer and more effective. Sugammadex seems to be, based on the evidence published to date as the best medication for this purpose. However, it would be expected that it would not provide the same benefits to patients with renal disease because of its clearance mechanism.

Case description

The patient is a 14-year-old patient with a history of chronic renal failure secondary to a vesicoureteral reflux, that led to left renal atrophy and hypertension. The patient had a NYHA II/IV functional class, no prior surgical or allergy history, and was scheduled for a left laparoscopic nephrectomy.

On physical examination she had good general conditions with ablood pressure of 156/74 mmHg, heart rate of 80 bpm, respiratory rate of 14 bpm, SaO₂ of 96 % at room air and weighed 42 kg. She had no predictors of difficult airway, normal cardiopulmonary auscultation without murmurs, normal breath sounds and no signs of respiratory distress. Abdominal examination was normal and presented no limb edema.

Laboratory results where: hemoglobin 11.7 g/ dL, a hematocrit of 35 %, creatinine 1.14 mg/ dL, BUN 21 mg/dL, an echocardiogram showed left ventricular hypertrophy and an ejection fraction of 75 % without any other abnormal findings.

She had noninvasive blood pressure monitoring, pulse oximetry, continuous ECG monitor, capnography, temperature, expiratory gas analysis, and neuromuscular block monitoring (TOF watch). The anesthetic induction was made with sevoflurane 8 % plus oxygen at 8:15 AM, a 2 mg bolus of midazolam was administered, afterwards. remifentanil was started at 0.1 μg per kg per minute and sevoflurane was decreased to 2 %. Then 4 mgs of dexamethasone, 60 mg lidocaine and 20 mg (0.5 mg per kg) of rocuronium were administered.

Once optimal conditions were obtained, laryngoscopy was performed observing a Cormack I visualization, and an oral tracheal intubation with a 6.5 mm tube was done, and its balloon filled with 2 mL of air and fixed at 17 cm with prior pulmonary auscultation. The mechanical ventilation was started in a volume control mode with a Vt 7 mL/kg, RR 14, PEEP 5 cmH2O, an I:E ratio of 1:2, and an FiO2 of 50 % with air.

Surgery began at 9 AM maintaining hemodynamic stability. At 9:30 AM at 10 mg bolus of rocuronium was provided to improve the conditions for laparoscopy obtaining a response of only one twitch out of four, for the rest of the surgical procedure which ended at 11:20 AM.

Thereafter, 3 mg of IV morphine for analgesia were administered, and the train of four still showed only one response. A moderate depth block was diagnosed, for which 100 mg (2 mg per kg) of IV sugammadex were administered. Continuous neuromuscular monitoring showed 100 % recovery of the four twitches 70 seconds after administration. Then sevoflurane was discontinued, and the FiO2 increased to 100 % and the patient was extubated fully awake, with a good breathing pattern and without signs of residual neuromuscular block.

She was monitored during her immediate postoperative period in which only analgesic rescue doses were required. No episodes of hyperventilation or desaturation suggestive of neuromuscular block were observed.

Discussion

The use of non-depolarizing neuromuscular relaxants demands proper knowledge by the anesthesiologist of their potential risks. Residual neuromuscular block along with allergic reactions are the most important adverse effects of their use (2).

The main published recommendations to reduce the risk of residual block are:

1. Avoid the use of long-acting relaxants

2. Use routine objective neuromuscular monitoring.

3. Avoid unnecessary deep paralysis.

4. Reverse the block once the second or third twitch out of four reappear.

5. Administer cholinesterase inhibitors early, 15 to 30 min before extubation instead of immediately before as commonly done.

6. Perform routine reversal. This is probably the most controversial recommendation as this reversal is not without risks.

The design and application of strict protocols of neuromuscular paralysis could reduce the incidence of residual block, although not completely eliminate it (3).

As described, it is necessary to devise new strategies to reduce the problem of residual block. Sugammadex seems to be one of the major advances in the management of neuromuscular relaxation. However, because of the clearance mechanism of the drug, the benefits of its use do not seem to apply to patients with renal diseases.

Sugammadex is a modified γ- cyclodextrin which acts as a selective agent that binds to steroidal neuromuscular blockers.

Cyclodextrins are hydro-soluble cyclic oligosaccharides which have been used in the food and cosmetic industry as solubilizers and stabilizers with high safety profiles and low toxicities. Currently many of the lipophilic medications are solubilized with the use of cyclodextrins as prostaglandins and dexamethasone among others (4).

The tridimensional structure of cyclodextrins is similar to a doughnut with a hydrophobic hole which encapsulates steroidal neuromuscular blockers (rocuronium and vecuronium), with an external hydrophilic surface which allows the formation of a hydro-soluble complex with limited biological activity, avoiding related adverse effects.

Sugammadex forms 1:1 complexes with steroidal neuromuscular blockers and has no affinity for nonsteroidal agents, with a high rate of association and very low rate of dissociation (1/25,000,000 complexes are dissociated).

The binding of sugammadex to free plasmatic rocuronium or vecuronium generates a concentration gradient that favors of movement towards plasma and the formation of new complexes of the molecules not bound to a neuromuscular junction. For this reason, the effect of neuromuscular blockers wears rapidly because of their diffusion from the neuromuscular junction. This results in an increase in the total plasmatic concentration of rocuronium or vecuronium (both free and bound to sugammadex) (5).

In the absence of sugammadex, rocuronium is cleared by biliary excretion (more than 75 %) and in lesser degree by the kidneys and feces. Due two the soluble nature of the sugammadexrocuronium complex, urinary excretion is the major routes of elimination (65 % to 97 %). Its metabolism is very limited, eliminated in an unaltered state.

Elimination half-life is approximately 1.8 hours. The estimated plasmatic clearance in adults is 88 mL per min.

The dose of sugammadex depends on the scenario to be used, as a relationship between the administered dose and the depth of block has been found and classified as:

• Moderate block (appearance of second twitch with the TOF): 2 mg per kg.

• Deep block (no response in the TOF, one or two post-tetanic counts): 4 mg per kg.

• Blocks in rapid sequence induction (immediate or rescue reversal): 16 mg per kg. In all of these scenarios, the TOF recovery, greater than 0.9, has been observed to occur in less than 3 min (6).

No study has reported an instance of recur - ring neuromuscular block after the initial reversal. The results of these studies have demonstrated the effectiveness of sugammadex for reversal of neuromuscular block induced by steroidal relaxants with few adverse effects. This could have important implications in current anesthetic practice, not only in terms of preventing residual block and its complications, but in scenarios of impossible to ventilate/impossible to intubate, or in rapid sequence intubation; moreover when anti-cholinesterase agents cannot reverse deep blocks and their adverse effects. The use of sugammadex could eventually replace succinylcholine.

Although the benefits shown by studies would apply to most of the population, the renal clearance of the sugammadex-steroidal blocker complex would not allow the use of this medication for the reversal of neuromuscular block in patients with renal disease. For this reason they would still be subject to the risk of residual block, inadequate intraoperative muscle relaxation and the adverse effects of anti-cholinesterase drugs.

Even though there are studies reporting the pharmacokinetic alterations of the medication because of reduced clearance of the sugammadex- rocuronium complex in patients with renal disease compared to healthy patients, it has been shown that reversal was as fast and effective as in the control group without any patient presenting any signs of block reappear ance, similar yo what happened with our patient (7,8).

CONCLUSIONS

The use of neuromuscular blockers demands adequate knowledge of their pharmacological properties to avoid undesired adverse effects, specifically in patients with comorbidities that alter their pharmacokinetic behavior. Even though sugammadex has been proposed as one of the solutions to avoid residual block, the pharmacokinetic alterations occuring in patients with chronic renal disease supossedly decreasing its clearance, this benefit may not be extensive to them. However, as shown in this case and in other studies, recovery time is similar to patients without renal disease.

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