Use of sugammadex on burn patients: descriptive study

Abstracts

OBJECTIVES:

A burn patient is a challenge for any anesthesiologist, undergoing several surgeries during admission, and requiring general anesthesia and muscle relaxation most of the times. The victim may have respiratory system impairment and a response to muscle relaxants that differs from the healthy patient, thus proper monitoring and reversal is crucial. We analyzed sugammadex effectiveness and safety in this population.

MATERIALS AND METHODS:

It was a prospectively descriptive study, including 4 patients, and all of them were considered major burn patients, who underwent escharotomy with general anesthesia and neuromuscular relaxation. The main variable was the time for recovery of a TOF higher than 0.9 after the administration of sugammadex before extubation.

RESULTS:

Mean time of recovery from a TOF ratio higher than 0.9 following the administration of Sugammadex was of 4.95 min 95% CI (3.25-6.64, p= .53).

CONCLUSIONS:

The reversion of neuromuscular relaxation with sugammadex appears to be effective and safe in the burn patient. More analytical, comparative studies of larger populations would be necessary to confirm these data.

Sugammadex; Cyclodextrin; Burn injury; Rocuronium; Neuromuscular block; Neostigmine

OBJETIVOS:

O paciente queimado representa um desafio para o anestesiologista, pois se submete a várias intervenções cirúrgicas durante sua hospitalização e necessita de anestesia geral e relaxamento muscular na maior parte delas. Apresenta sistema respiratório comprometido e uma resposta aos relaxantes musculares que difere do paciente sadio; portanto, um monitoramento correto e reversão tornam-se imprescindíveis. Avaliamos a eficácia e segurança do sugamadex nessa população.

MATERIAL E MÉTODOS:

Estudo descritivo com caráter prospectivo que inclui quatro pacientes, todos eles considerados grandes queimados, submetidos a escarectomia com anestesia geral e relaxamento neuromuscular. Como variável principal tomou-se o tempo de recuperação de TOF superior a 0,9 após a administração de sugamadex antes de extubação.

RESULTADOS:

O tempo médio de recuperação de uma razão TOF superior a 0,9 após a administração de sugamadex foi de 4,95 minutos (IC95% 3,25-6,64; p = 0,53).

CONCLUSÕES:

A reversão do relaxamento neuromuscular com sugamadex parece ser eficaz e segura no paciente queimado. Seriam necessários mais estudos analíticos, comparativos e de maior população para confirmar esses dados.

Sugamadex; Gama-ciclodextrinas; Queimaduras; Androstanóis; Bloqueio neuromuscular; Neostigmina

OBJETIVOS:

El paciente quemado supone un reto para el anestesista, pues se somete a varias intervenciones quirúrgicas durante su ingreso, requiriendo anestesia general y relajación muscular en la mayor parte de ellas. Presentan un sistema respiratorio comprometido y una respuesta a los relajantes musculares que difiere de la del paciente sano, por lo que se hace imprescindible una correcta monitorización y reversión. Valoramos la efectividad y seguridad del sugammadex en esta población.

MATERIAL Y MÉTODOS:

Estudio descriptivo con carácter prospectivo que incluyó a 4 pacientes, todos ellos considerados grandes quemados, sometidos a escarectomía con anestesia general y relajación neuromuscular. Como variable principal se tomó el tiempo de recuperación de un TOF superior a 0,9 tras la administración de sugammadex previa a extubación.

RESULTADOS:

El tiempo medio de recuperación de un TOF ratio superior a 0,9 tras la administración de sugammadex fue de 4,95 min, IC al 95% (3,25-6,64; p = 0,53).

CONCLUSIONES:

La reversión de la relajación neuromuscular con sugammadex parece ser efectiva y segura en el paciente quemado. Serían necesarios más estudios de índole analítica, comparativa y de mayor población para confirmar dichos datos.

Sugammadex; Ciclodextrina; Quemadura; Rocuronio; Boqueo neuromuscular; Neostigmina

Introduction

Burns are tissue injuries produced by skin aggression from any source of energy. The severity criteria would be involvement of more than 25% of total body surface, burns that follow inhalation syndrome, involvement of face, eyes, hands, feet and perineum. ¹ Mortality of major burn patients is approximately 13.9%.^{2 and 3} In our unit, 174 patients were attended in the year of 2012. These patients underwent several surgical interventions during their stay in the hospital, with most of them under general anesthesia, orotracheal intubation, and neuromuscular relaxation.

Sugammadex is a modified cyclodextrin used for reversion of rocuronium- and vecuronium-induced nondepolarizing muscle block. ^{4 and 5} The dose of sugammadex varies depending on the level of muscle relaxation, with mean time for recovery of a TOF ratio higher than 0.9 of 3 min. (min). ^{6 and 7} Several studies demonstrated the superiority of this drug compared to neostigmine^{8 , 9 and 10} regarding safety and time for recovery. It was successfully used in the obese patient, in the elderly, and also in children older than two years. ¹¹ However, its use in the major burn patient had not been studied. The main objective of this work was to analyze the efficacy of sugammadex in this patient profile in whom the metabolic-hemodynamic changes may alter its pharmacology and in whom, due to respiratory system involvement (if constant), an appropriate reversal of neuromuscular blockers is crucial. Secondary objectives are the measurement of neuromuscular relaxation recovery time after its administration, the comparison of these results with those existing in the literature in other types of patients, report of the emergence of adverse effects related to its administration, and report of main anesthetic considerations of major burn patient.

Materials and methods

A prospective descriptive study of four cases was conducted over two months. Inclusion criteria were as follows: major burn patient who underwent escharotomy under general anesthesia and orotracheal intubation. Exclusion criteria were: allergy to sugammadex, severe renal impairment (creatinine clearance below 30 mL min^-1, intraoperative hemodynamic instability requiring administration of amines, or the need for blood transfusions. All patients were monitored with electrocardiogram, oxygen saturation, noninvasive blood pressure and monitoring of neuromuscular blockade by accelerometry (TOF watch). Induction was conducted with propofol (2.5 mg kg^-1), fentanyl (2 µg kg^-1) and rocuronium (0.6 mg kg^-1). Maintenance was performed with sevoflurane at 1 CAM, with the administration of a booster dose of relaxant (30% the initial dose) on those who showed recovery from block (emergence of 2 responses in TOF). At the end of the surgery, and before extubation, sugammadex was administered in all cases, with the dose according to the level neuromuscular block (deep block 4 mg kg^-1, moderate block 2 mg kg^-1, recovery phase with 4 responses to TOF ratio 1 mg kg^-1). The patients were extubated after recovery of TOF higher than 0.9. The variable considered was time in minutes since the administration of sugammadex until recovery of TOF higher than 0.9. All the time we followed the ethical standards of the human experimentation committee of our center. For data analysis, we used the software IBM SPSS Statistics 22.0.

Results

Four patients with ages between 69 and 76 years were included. The clinical characteristics of the patients are summarized in Table 1, and Fig. 1 shows one of the patients included in the study. The average percentage of body surface area burned was 17.25%. Two of the patients received a booster dose of rocuronium (20 and 25 mg respectively). The average recovery time from a TOF ratio greater than 0.9 after sugammadex administration before extubation was 4.95 min with a 95% confidence interval of 3.25-6.64 (p = 0.53). The median of the same variable was of 4.65 min. Typical deviation was of 1.06.

Table 1
Patients' clinical characteristics.

Case	Patient 1	Patient 2	Patient 3	Patient 4
Age (years)	76	77	69	72
Gender	Female	Female	Male	Female
Comorbidity	Hypertension, dyslipidemia, depression	Hypertension, osteoporosis	Dementia, blindness	Hypertension
Burn body surface (%)	18	12	25	14
Time for recovery of TOF higher than 0.9 min	4.2	5.1	4.1	6.4
Booster dose of rocuronium (mg)	No	20	No	25

Figure 1
A patient included in the study.

Discussion

The involvement of the respiratory system is almost constant in major burn patients; there is vasodilation that contributes to respiratory mucosa edema and increased permeability of lung capillaries, ¹² and therefore the control of lung function shall be our priority. In severe burn patients, there is a proliferation of immature acetylcholine receptors on both neuromuscular plate and extra-synaptic sites. This leads to an increased sensitivity to depolarizing relaxants (succinylcholine), with risk of severe hyperkalemia and a resistance to non-depolarizing neuromuscular blocking agents, increasing instauration latency, and reducing the time of action¹³; this, along with a possible renal impairment may result in its accumulation after readministration, with risk of residual curarization. The use of muscle relaxation reversion agents, and its monitoring are effective measures to prevent paresis; the presence of TOF ratio greater than 0.9 is considered safe to perform extubation. ¹⁴ The anticholinesterase drugs (neostigmine, edrophonium) are routinely used for reversal of neuromuscular relaxation in burn patients; these drugs produce adverse effects derived from the increase of acetylcholine and its interaction with muscarinic receptors out of intersynaptic site. The average time to reach a TOF value higher than 0.9 after the reappearance of the 2 responses to TOF is of 18.5 min after neostigmine administration. ¹⁵ It is shown ineffective to reverse deep block. The emergence of sugammadex assumed to be a revolution in this regard, but it has not been studied in burn patients, with a more rapid and predictable beginning of action being demonstrated in several studies, compared to neostigmine, and being effective in a deep block. ^{8 , 9 , 10 and 11} In our study the mean time to recovery of TOF ratio greater than 0.9 after sugammadex administration was 4.95 min, time that is lower than that of neostigmine in other populations. None of the patients showed complications related to the administration of sugammadex. These data, although preliminary, have shown that sugammadex can be used in these patients, with recovery times for muscle activity similar to that in other types of patients. More prospective comparative analytical studies with more patients are necessary to confirm the results of this work.

References

• ¹
  Latenser BA. Critical care of the burn patient: the first 48 hours. Crit Care Med. 2009;37:2819-26.
• ²
  Steinvall I, Fredrikson M, Bak Z, et al. Mortality after thermal injury: no sex-related difference. J Trauma. 2011;70:959-64.
• ³
  Brusselaers N, Monstrey S, Vogelaers D, et al. Severe burn injury in Europe: a systematic review of the incidence, etiology, mor- bidity, and mortality. Crit Care. 2010;14:R188.
• ⁴
  Zhang MQ. Drug-specific cyclodextrins: the future of rapid neu- romuscular block reversal?. Drugs Fut. 2003;99:632-7.
• ⁵
  Bom A, Bradley M, Cameron K, Clark K, Van Egmond J, Feil- den H, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin-based synthetic host. Angew Chem Int Ed Engl. 2002;41:266-70.
• ⁶
  Duvldestin P, Kuizenga K, Saldien V, et al. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium-or vecuronium induced neuromuscular blockade under sevoflurane anesthesia. Anesth Analg. 2010;110:74-82.
• ⁷
  Suy K, Morias K, Cammu G, et al. Effective reversal of mode- rate rocuronium or vecuronium-induced neuromuscular block whit sugammadex, a selective relaxant binding agent. Anesthe- siology. 2007;106:283-8.
• ⁸
  Jones RK, Caldwell F E, Brull SJ, et al. Reversal of profound rocuronium-induced blockade at extubation: a randomized comparison whit neostigmine. Anesthesiology. 2008;109:816-24.
• ⁹
  Khuenl-Brady KS, Wattwil M, Vanacker BF, et al. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomi- zed, controlled trial. Anesth Analg. 2010;110:64-73.
• ¹⁰
  Paton F, Paulden M, Chambers D, et al. Sugammadex pro- vided significantly faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine. Br J Ana- esth. 2010;105:558-67.
• ¹¹
  Plaud B, Meretoja O, Hofmockel R, et al. Reversal of rocuronium-induced neuromuscular blockade with sugamma- dex in pediatric and adult surgical patients. Anesthesiology. 2009;110:284-94.
• ¹²
  Cantal E, Gouturbe P, Asencio Y, et al. Reanimation et anesthesie du brule la´dulte. Paris: EMC; 2008.
• ¹³
  Gasca PJD. Anestesia en el paciente quemado. Rev Mex Anest. 2013;36:327-30.
• ¹⁴
  Plaud B, Debaene B, Donati F, et al. Residual paralysis after emergence from anesthesia. Anesthesiology. 2010;112: 1013-22.
• ¹⁵
  Blobner M, Eriksson LI, Scholz J, et al. Reversal of rocu- ronium induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol. 2010;27:874-81.

Publication Dates

• Publication in this collection
  Aug 2015

History

• Received
  13 Aug 2014
• Accepted
  08 Oct 2014