BLOQUEADORESNEUROMUSCULARESENELPACIENTEQUEMADO.

UnidaddeAnestesia-TerapiaIntensiva

Dr.MarcoAntonioGarnicaEscamilla.

EPIDEMIOLOGÍA

•  Problemadesaludpúblicamundial•  Elevadamorbi–mortalidad•  2013

– 35millonesdelesionesporquemadurasanivelmundial

– 2.9millonesdehospitalizaciones– 238,000muertes

StemCellRevandRepDOI 10.1007/s12015-017-9721-9

TripatheeandBasnetBurns&Trauma(2017)5:10

EPIDEMIOLOGÍA• Causa importante de trauma en todo el mundo

• Afecta a todas las edades

• 300,000 muertes/año

• 1 millón en Estados Unidos

• FR: Hombre, extremos de la vida, abuso de alcohol, asilos

Med Intensiva. 2016;40(1):49-59

EPIDEMIOLOGÍA

•  Extremosdelavida

•  Edadproduc?va(25a64años)

•  80-90%relacionadasconfuego

•  Quemaduraeléctrica(hombres)

Int.J.Environ.Res.PublicHealth2017,14,381;doi:10.3390/ijerph14040381

JournalofPublicHealth|Vol.35,No.3,pp.384–396|doi:10.1093/pubmed/fds102|

EPIDEMIOLOGÍA

with 9.95% and they were: local infection in 74, lysisof implants in 18, hemorrhages in the gastrointes-tinal tract in one, and sepsis and organ failure innine patients.

The mortality of patients was nine; and the causesof death were: multiple organ failure and sepsis ineight, and hemorrhage of the gastrointestinal tract inone. Seven patients presented burns of more than60% of these groups, one patient died. The percent-age of mortality was of 0.87% and DL-50 calculationwas of 75.6%. The children with extensive burns(more than 40% of the body surface burnt) were 31and six died (19.35%) (Table 1).

The children who were treated in our hospital inthe acute phase were 77.6%, of this three died. Thechildren who were at first in other hospitals and latercame to continue their treatment were 22.4%, of thisgroup five patients died. Three groups were formedaccording to the time they began hydration: the firstgroup within the first 4 hours (33.6%), 32 had com-plications and three died. The second group between4 and 8 hours (29.7%), 32 had complications and fourpatients died. The third group, after 8 hours (34.7%),of these 38 had complications and two died.

The Characteristics of the Burns Accordingto Their EtiologyBurns caused by liquids had two modalities: one dueto scalding or splashing and the other one due toimmersion in hot liquids.

Scalding. This group included 590 (57.56%) chil-dren with an average hospital stay of 15.18 days. Theaverage of burnt body surface in this group was11.5%. The depth of the burns in this group was58.8% with superficial second degree, 38.3% withdeep second degree, and 2.8% with third degree. Theextensive affected areas were: thorax and upper limbsin 85%; the remaining 15% were located in the lowerlimbs. Two hundred sixty-eight children requiredsurgeries (45.42%) and 322 did not require it(54.58%) because these were superficial injuries.Complications in this group were 30. There was onedeath.

Immersion. This group included 204 (19.90%)children with an average hospital stay of 12.9 days.The average of burnt body surface in this group was12.8%. The depth of the burns in this group was

78%

11%

4%

4%

3%

0%Hot liquidsFlameElectricityDeflagrationContactChemical

Figure 2. Burns etiology in burnt children.

Table 1. Correlation between burns percentage andmortality in children

TBSA (%) Cases Dead % of Dead

1–10 544 0 011–20 299 0 021–30 101 1 0.931–40 50 2 441–50 17 2 1151–60 7 2 2861–70 4 0 071–80 2 1 5081–90 1 1 100Total 1025 9 0.87

0

50

100

150

200

250

0 2 4 6 8 10 12 14

Figure 1. Age frecuency in burns children. The major percentage of burns in children was in the first 3 years old.

Journal of Burn Care & Research470 Cuenca-Pardo, Alvarez-Dıaz, and Compres-Pichardo May/June 2008

JBurnCareRes2008;29:468–474)

EPIDEMIOLOGÍA

with 9.95% and they were: local infection in 74, lysisof implants in 18, hemorrhages in the gastrointes-tinal tract in one, and sepsis and organ failure innine patients.

The mortality of patients was nine; and the causesof death were: multiple organ failure and sepsis ineight, and hemorrhage of the gastrointestinal tract inone. Seven patients presented burns of more than60% of these groups, one patient died. The percent-age of mortality was of 0.87% and DL-50 calculationwas of 75.6%. The children with extensive burns(more than 40% of the body surface burnt) were 31and six died (19.35%) (Table 1).

The children who were treated in our hospital inthe acute phase were 77.6%, of this three died. Thechildren who were at first in other hospitals and latercame to continue their treatment were 22.4%, of thisgroup five patients died. Three groups were formedaccording to the time they began hydration: the firstgroup within the first 4 hours (33.6%), 32 had com-plications and three died. The second group between4 and 8 hours (29.7%), 32 had complications and fourpatients died. The third group, after 8 hours (34.7%),of these 38 had complications and two died.

The Characteristics of the Burns Accordingto Their EtiologyBurns caused by liquids had two modalities: one dueto scalding or splashing and the other one due toimmersion in hot liquids.

Scalding. This group included 590 (57.56%) chil-dren with an average hospital stay of 15.18 days. Theaverage of burnt body surface in this group was11.5%. The depth of the burns in this group was58.8% with superficial second degree, 38.3% withdeep second degree, and 2.8% with third degree. Theextensive affected areas were: thorax and upper limbsin 85%; the remaining 15% were located in the lowerlimbs. Two hundred sixty-eight children requiredsurgeries (45.42%) and 322 did not require it(54.58%) because these were superficial injuries.Complications in this group were 30. There was onedeath.

Immersion. This group included 204 (19.90%)children with an average hospital stay of 12.9 days.The average of burnt body surface in this group was12.8%. The depth of the burns in this group was

78%

11%

4%

4%

3%

0%Hot liquidsFlameElectricityDeflagrationContactChemical

Figure 2. Burns etiology in burnt children.

Table 1. Correlation between burns percentage andmortality in children

TBSA (%) Cases Dead % of Dead

1–10 544 0 011–20 299 0 021–30 101 1 0.931–40 50 2 441–50 17 2 1151–60 7 2 2861–70 4 0 071–80 2 1 5081–90 1 1 100Total 1025 9 0.87

0

50

100

150

200

250

0 2 4 6 8 10 12 14

Figure 1. Age frecuency in burns children. The major percentage of burns in children was in the first 3 years old.

Journal of Burn Care & Research470 Cuenca-Pardo, Alvarez-Dıaz, and Compres-Pichardo May/June 2008

JBurnCareRes2008;29:468–474)

•  Elevadoscostos

•  Largasestanciasintrahospitalarias

•  Múldplesprocedimientoquirúrgicos

Med Intensiva. 2016;40(1):49---59

www.elsevier.es/medintensiva

REVIEW

Initial evaluation and management of the critical burnpatient

C. Vivóa, R. Galeirasb,∗, Ma D.P. del Cazc

a Servicio de Anestesiología y Reanimación, Hospital Universitario y Politécnico La Fe, Valencia, Spainb Servicio de Medicina Intensiva, Complejo Hospitalario Universitario de A Coruna (CHUAC), Instituto de Investigación Biomédicade A Coruna (INIBIC), SERGAS, Universidade da Coruna (UDC), A Coruna, Spainc Servicio de Cirugía Plástica, Hospital Universitario y Politécnico La Fe, Valencia, Spain

Received 22 September 2015; accepted 25 November 2015Available online 24 December 2015

KEYWORDSBurns;Initial management;Inhalation injury

Abstract The major improvement in burn therapy is likely to focus on the early managementof hemodynamic and respiratory failures in combination with an aggressive and early surgicalexcision and skin grafting for full-thickness burns.

Immediate burn care by first care providers is important and can vastly alter outcomes, andit can significantly limit burn progression and depth. The goal of prehospital care should beto cease the burning process as well as prevent future complications and secondary injuriesfor burn shock. Identifying burn patients appropriate for immediate or subacute transfer is animportant step in reducing morbidity and mortality. Delays in transport to Burn Unit should beminimized.

The emergency management follows the principles of the Advanced Trauma Life SupportGuidelines for assessment and stabilization of airway, breathing, circulation, disability, exposureand environment control.

All patients with suspected inhalation injury must be removed from the enclosure as soon aspossible, and immediately administer high-flow oxygen. Any patient with stridor, shortness ofbreath, facial burns, singed nasal hairs, cough, soot in the oral cavity, and history of being ina fire in an enclosed space should be strongly considered for early intubation. Fibroscopy mayalso be useful if airway damage is suspected and to assess known lung damage.

Secondary evaluation following admission to the Burn Unit of a burned patient suffering asevere thermal injury includes continuation of respiratory support and management and treat-ment of inhalation injury, fluid resuscitation and cardiovascular stabilization, pain control andmanagement of burn wound.© 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

∗ Corresponding author.E-mail address: ritagaleiras@hotmail.es (R. Galeiras).

http://dx.doi.org/10.1016/j.medin.2015.11.0100210-5691/© 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Protocolos de resucitación

Soporte respiratorio

Control de infecciones

Inicio de nutrición de manera temprana

Excisión temprana

Cierre de heridas

50 C. Vivó et al.

PALABRAS CLAVEQuemaduras;Manejo inicial;Síndrome deinhalación

Evaluación inicial y manejo del paciente quemado crítico

Resumen Los principales avances en el tratamiento de la quemadura se centran en el manejoprecoz de la disfunción hemodinámica y respiratoria junto con la excisión quirúrgica agresiva yprecoz y el injerto de piel en quemaduras de espesor total.

La atención inmediata a la quemadura puede cambiar el pronóstico, limitando significativa-mente su progresión y profundidad. El objetivo de la asistencia prehospitalaria es detener elproceso de combustión así como prevenir posteriores complicaciones y danos secundarios alshock por quemadura. Identificar los pacientes quemados subsidiarios de traslado inmediato esimportante en términos de morbilidad y mortalidad. La demora en el traslado a una Unidad deQuemados de referencia debe ser minimizada.

El manejo emergente debe ser el mismo que para cualquier otro paciente politraumatizado,con evaluación y estabilización de la vía aérea, la respiración, la circulación, la discapacidad yel control ambiental.

Todos los pacientes con sospecha de inhalación deben ser trasladados del recinto tan prontocomo sea posible y administrar inmediatamente oxígeno a alto flujo. Ante un paciente con estri-dor, dificultad para respirar, quemaduras faciales, vibrisas quemadas, tos, hollín en la cavidadoral e historia de inhalación de humo en un lugar cerrado debe ser considerada la indicaciónde intubación precoz. La fibroscopia puede ser útil si se sospecha dano de la vía aérea y paraevaluar el dano pulmonar conocido.

La valoración secundaria tras el ingreso en la Unidad de un paciente que ha sufrido una lesióntérmica grave incluye la continuación del soporte respiratorio y el manejo y tratamiento deldano por inhalación, la reanimación con líquidos y la estabilización cardiovascular, el controldel dolor y el manejo de la herida.© 2015 Elsevier España, S.L.U. y SEMICYUC. Todos los derechos reservados.

Introduction

Burns remain a major cause of traumatic injury world-wide affecting all ages. Burn injuries account for more than300,000 deaths worldwide each year.1

Major risk factors for burns include male gender, extremeyouth or old age, alcohol abuse, and substandard housingresidence.

In the last half century a best understanding of theprinciples of care burn have resulted in improved survivalrates, shorter hospital stays and decreases in morbidity andmortality rates due to the development of resuscitationprotocols, improved respiratory support, infection control,early nutrition enteral and early excision and burn woundclosure.2---4

Other factors, including immediate prehospital care,early emergency treatment with advanced life support capa-bility and secondary transfer to a Burn Unit have contributedto improve substantially survival of severe burns patients.5

Major burns in adult patients are defined as thermalinjury-induced lesions which justify intensive care treat-ment for at least 3 days post-injury (Table 1).6

Summary of pathophysiology

The efficiency of the initial chain of medical care is essen-tial in improving outcome, specifically in severe burns. Thisapproach leads to a better understanding of pathophysiolo-gical mechanisms involved in burn shock.

Table 1 Criteria for the diagnosis of major burns.5

Total body surface area burned >25% in adults or >20% atextremes of age

Full thickness burns >10%Burns involving critical areas: hands, feet, face, neck,

perineum, genital areaInhalation injury associatedElectrical or lightning burnsCircumferential burns on the extremities or chestChemical burns with threat of cosmetic or functional

compromiseAsociated traumaBurns in patient with serious pre-existing disease (>ASA II)

ASA, American Society of Anesthesiologists.

Major burns cause massive tissue destruction and resultin activation of a cytokine-mediated inflammatory responsethat leads to dramatic pathophysiologic effects at sites localand distant from the burn. The systemic effects occur intwo distinct phases, a burn shock (ebb) phase followed by ahypermetabolic (flow) phase.

Generalized edema even in non-injured tissues occurswhen the injury exceeds 25---30% total body surface area(TBSA). After major burn injury, continued loss of plasmainto burned tissue can occur up to the first 48 h or evenlonger.

Loss of intravascular fluid into burned areas and edemaformation (in nonburned sites) can quickly result in burnshock with impaired tissue and organ perfusion. Thus, the

Med Intensiva. 2016;40(1):49-59

Usodeanestesiageneral.

•  Momentodelingreso.•  Durante los primeros días (curaciones,escarectomías, desbridamientos e injertosdermoepidérmicos)

•  Comoenformaelecdva(cirugíareparadora).

–  VíaAéreayVendlaciónMecánica–  CambiosFarmacológicos–  ControldedoloryTemperatura

Anesthesiology2015;122:448-64)

QUEMADURAGRAVE.

Hipoperfusión tisular

Catecolaminas

VO2

Tasa metabólica

Hipermetabolismo

VO2

GC

GER

Perdida de K+ y N+

Temperatura

EBB

FLOWe-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e308–e312

ValoraciónPreoperatoria

•  Fasesdeltratamiento– Agudo:0a72horas– Hipermetabólico:quintodíahastaelcierredelauldmalesión

– Secuelas:todalavida

Anesthesiology2015;122:448-64)

máximo a las 2 semanas. pudiendo llegar a meses en los grandes quemados, respuesta normal después de 3 años para el atracurio y el vecuronio

LacausadeestarespuestaanormalalosBNM

•  Cambiosenlauniónneuromuscular.

•  Cambiosfarmacocinédcos.

•  Factoresneurohumorales.

•  Presenciadecomorbilidades.

Cambiosenlauniónneuromuscular

NuevasvíasdeEliminación

Cl

VdV1

JBurnCareRes2015;36:e194–e211

UniónaProteínas

•  DisminucióndeAlbúmina•  AumentaGlicoproteínaácidaα-1(GAA-1)•  DilcillaesdmacióndelVolumendeDistribuciónaparente

•  AumentalaFracciónLibre

JBurnCareRes2015;36:e194–e211

Factores neurohumorales

Succinilcolina

Hay una gran dispersión entre las diferentes publicaciones en cuanto al momento en que aparece este riesgo aumentado, desde las primeras 24 h hasta siete días después de ocurrida la quemadura

La duración de esta respuesta alterada es variable, pero se ha descrito hasta 2 años después de una injuria térmica mayor

Una dosis de 0,1-0,2 mg·kg-1 produce un bloqueo máximo mayor al 80%, sin modificar los niveles de potasio

ANESTHETIC PHARMACOLOGY INTERNATIONAL SOCIETY FOR ANAESTHETIC PHARMACOLOGYSECTION EDITORJAMES G. BOVILL

Neuromuscular Pharmacodynamics of Rocuronium inPatients with Major BurnsTaeHyung Han, MD, PhD, FAAFP*, HyeongSeok Kim, MD*, JiYoung Bae, MD*,KwangMin Kim, MD, PhD*, and J. A. Jeevendra Martyn, MD, FRCA, FCCM†

*Department of Anesthesiology and Pain Medicine, Hangang Sacred Heart Hospital, Hallym University, School ofMedicine, Seoul, Korea; and †Department of Anesthesiology and Critical Care, Harvard Medical School, MassachusettsGeneral Hospital, and Shriners Hospital for Children, Boston, Massachusetts

Rocuronium, which has a short onset time and is free ofhyperkalemic effects, could be considered for rapid-sequence induction of anesthesia in patients withburns. In this study, we assessed the neuromuscularpharmacodynamics of rocuronium in patients with ma-jor burns. Adults aged 18–59 yr who had a major burninjury (n ! 56) and a control group of 44 nonburnedpatients were included. Rocuronium was used at 3times (0.9 mg/kg) or 4 times (1.2 mg/kg) the 95% effec-tive dose. Anesthesia consisted of propofol and fenta-nyl with nitrous oxide and oxygen. Neuromuscularblock was monitored with an acceleromyograph by us-ing train-of-four stimulation. The onset time to 95%

neuromuscular block was prolonged in burned com-pared with nonburned patients (115 " 58 s versus 68 "16 s for 0.9 mg/kg; 86 " 20 s versus 57 " 11 s for 1.2 mg/kg). Dose escalation shortened the onset time, pro-longed the duration of action, and improved intubatingconditions in burned patients. All recovery profileswere significantly shorter in burned versus nonburnedgroups with both doses. Resistance to the neuromuscu-lar effects of rocuronium was partially overcome by in-creasing the dose. A dose up to 1.2 mg/kg providesgood tracheal intubating conditions after major burns.

(Anesth Analg 2004;99:386–92)

A fter major thermal injury, situations may arisein which rapid onset of paralysis is required,such as for rapid-sequence induction of anes-

thesia or for treatment of laryngospasm. Use of succi-nylcholine is contraindicated because of concernsabout hyperkalemia (1). Rocuronium has a fast onsettime, an intermediate duration of action, and no hy-perkalemia and may well be a suitable alternative tosuccinylcholine in these circumstances.

Patients with thermal injury are resistant to theaction of nondepolarizing muscle relaxants (NDMRs)(2,3). This effect takes up to several days to manifestand can be observed even up to 18 mo after burnwounds have healed (4). Resistance to NDMRs occursonly when burn injury covers more than 30% of total

body surface area (TBSA) (3). The molecular pharma-cologic explanation for this is that burn injury causesproliferation of acetylcholine receptors (AChR) on themuscle membrane located under burn sites, as well asat sites distant from the injury (2,5–7). An increase inAChR numbers is usually associated with resistance tothe neuromuscular blocking effects of NDMRs and anincreased sensitivity to depolarizing muscle relaxants(8). The clinical implication of this observation is thatburned patients require larger doses of NDMRs toachieve the desired effect. Rocuronium continues to bethe drug of choice when succinylcholine is contrain-dicated and a rapid onset of paralysis is necessary.However, the pharmacodynamic behavior of rocuro-nium has not been established in severely burnedpatients.

This prospective study was conducted to assess theonset time and duration of action of neuromuscularblock induced by a single dose of rocuronium (0.9 or1.2 mg/kg) in patients with major burns when com-pared with unburned patients.

MethodsThe study protocol was reviewed and approved bythe institutional ethics committee for human research

Presented in part at the 11th annual meeting of the EuropeanSociety of Anaesthesiologists with the Association of Anaesthetistsof Great Britain and Ireland, Glasgow, Scotland, May 31 to June 3,2003.

Accepted for publication April 5, 2004.Address correspondence and reprint requests to TaeHyung Han,

MD, PhD, FAAFP, Department of Anesthesiology and Pain Medi-cine, Hangang Sacred Heart Hospital, Hallym University, School ofMedicine, 94-200 Yongdungpo-Dong, Yongdungpo-Ku, Seoul, Ko-rea 150-719. Address e-mail to athan@unitel.co.kr.

DOI: 10.1213/01.ANE.0000129992.07527.4B

©2004 by the International Anesthesia Research Society386 Anesth Analg 2004;99:386–92 0003-2999/04

Vecuronium pharmacokinetics in patients with major burns†

K. R. Vega-Villa1, K. Kaneda2, S. Yamashita3, S. Woo1* and T. H. Han4*

1 Department of Pharmaceutical Sciences, College of Pharmacy, CPB 331, University of Oklahoma Health Sciences Center, 1110 N. StonewallAve., Oklahoma City, OK 73117, USA2 Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Yamaguchi, Japan3 Emergency Medical Center, Tokuyama Central Hospital, Yamaguchi, Japan4 Department of Anaesthesiology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA

* Corresponding author. E-mail: sukyung-woo@ouhsc.edu; AnthonyHan3@gmail.com

Editor’s key points

† Pharmacokinetics changeswith burn injury wereexamined as possiblemechanisms of resistance tovecuronium.

† BURN was the single mostsignificant covariate thatexplained the alteredvecuronium disposition inburns.

† Among burn patients, nophysiological factor useful forpredicting or guidingvecuronium dose was found.

† The altered drug distributionmay partially explain theknown resistance tovecuronium in burns.

Background. Burn patients develop resistance to non-depolarizing neuromuscularblocking agents (NDNMBAs) and require a significantly large dose to produce a desiredclinical response. Pathophysiological changes related to burn injury may alterpharmacokinetics (PK) and pharmacodynamics of NDNMBAs. The purpose of this studywas to compare vecuronium PK in burns vs non-burns.

Methods. Twenty adults, aged 23–58 yr, with 27–81% total body surface area (TBSA)burn, were studied at 4–57 post-burn days and compared with age- and sex-matched,non-burn controls. Vecuronium 0.12 mg kg21 was given i.v. as a single bolus within 10 s.Blood samples (n¼20) were collected over 12 h at predetermined time points.NONMEM was used to describe plasma drug concentration–time profiles for burns andnon-burns.

Results. A three-compartment model best described vecuronium concentration–timeprofiles. Burn patients showed enhanced distributional clearance at the terminal phase(0.12 vs 0.095 litre min21, P,0.0001), which yielded shorter elimination half-life forvecuronium (5.5 vs 6.6 h, P,0.001). BURN was the single most significant covariate thatexplained the altered vecuronium disposition in burns.

Conclusions. The altered drug distribution between tissues may partially explain theknown resistance to vecuronium in patients with major burns.

Keywords: burns; neuromuscular block; population pharmacokinetics; vecuronium

Accepted for publication: 23 July 2013

Burn patients develop resistance to non-depolarizing neuro-muscular blocking agents (NDNMBAs) and require significantlylarge doses to produce desired clinical response. This resistanceincreases over the course of therapy and depends on theextent of injury.1 Pathophysiological changes in cardiovascu-lar, respiratory, hepatic, and renal functions after burn injurymay alter the pharmacokinetics (PK) and pharmacodynamicsof NDNMBAs.1 – 3 The earlychanges during burn shock stage im-mediately after the injury include protein loss, oedema forma-tion, fluid accumulation in the lungs, and reduced cardiacoutput with decreases in hepatic and renal blood flow. In thesubsequent hyperdynamic hypermetabolic phase, cardiacoutput increases to provide healing wounds a higher supplyof energy and micronutrients. This augmented cardiacoutput enhances organ blood flow to the liver and kidneys,although full function is not regained.2

Vecuronium has been used for tracheal intubation as anadjunct to anaesthesia due to its relatively short duration of

action and minimal cardiovascular effects. Although vecuroniumPK has been described in normal subjects4–6 and other critical ill-nesses,7 8 its role to burn injury-related NDNMBA-resistance hasnot been well investigated. We hypothesize that pathophysio-logical changes caused by burn injury may alter vecuroniumconcentration decay over time and contribute to NDNMBA-resistance. To this end, we compared vecuronium dispositioncharacteristics in burns vs non-burns as a possible mechanismof resistance.

MethodsPatientsThe protocol was approved by the Institutional Ethics Com-mittee for Human Subjects. Written informed consent wasobtained from each participant. Twenty adults, aged 23–58,who suffered from .20% TBSA burn, without any renal orliver dysfunction, were enrolled. Age- and sex-matched,

† A part of this work was presented during the 2010 Annual Meeting of American Society of Anaesthesiologists, San Diego, CA, USA.

British Journal of Anaesthesia 112 (2): 304–10 (2014)Advance Access publication 25 September 2013 . doi:10.1093/bja/aet309

& The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.For Permissions, please email: journals.permissions@oup.com

Copyright © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Special Article

Critical Care Medicine www.ccmjournal.org 2079

healthcare services (consultant/speaker bureau for Hospira, HillRom, and she is owner of Critical Care Learning Curves business focused on critical care continuing education) and disclosed other healthcare professional organization activities (active member of Old Salem AACN and National Member as well). Dr. Pino disclosed family relationships with makers of healthcare products (spouse employed by Genentech). Dr. Rochwerg disclosed healthcare professional organization activities (Guideline meth-odologist for ATS, Candian Blood services, American Hematology Soci-ety). Dr. Friederich Murray disclosed healthcare professional organization activities with the Hypersomnia Foundation (with providers of healthcare services). Dr. Mehta disclosed healthcare professional organization activities (Guideline committee membership ATS ACCP liberation from Mechanical Ventilation). The remaining authors have disclosed that they do not have any potential conflicts of interest.For information regarding this article, E-mail: mjmurray3@gmail.com

Objective: To update the 2002 version of “Clinical practice guide-lines for sustained neuromuscular blockade in the adult critically ill patient.”Design: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromus-cular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guide-lines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided.Methods: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommen-dations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was avail-able to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, sugges-tions, or good practice statements for these 21 questions.Results: The Task Force developed a single strong recommenda-tion: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous

Copyright © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.DOI: 10.1097/CCM.0000000000002027

1Geisinger Medical Center, Danville, PA. 2Albany Medical Center, Albany, NY. 3University of Arizona College of Pharmacy, Tucson, AZ. 4Clinic Medical Center, Burlington, MA. 5Indiana University, Indiana, IN. 6Grand Strand Medical Center, Myrtle Beach, SC. 7Baystate Medical Center, Springfield, MA. 8Saint Elizabeth's Medical Center, Boston, MA. 9University of Toronto, Toronto, Canada.10Riverside Medical Group, Yorktown, VA.11University of Nebraska Medical Center, Omaha, NE.12Novant Health, Clemmons, NC.13Massachusetts General Hospital, Boston, MA.14Mayo Clinic, Rochester, MN.15Lancaster General Hospital, Lancaster, PA.16McMaster University, Hamilton, Ontario, Canada.17Medscape, New York, NY.18University of Toronto, Toronto, Canada.Dr. Murray disclosed participating in healthcare professional organization activities with ASA (Committee Member) and TAS BOD. Dr. Erstad dis-closed non-governmental research funding with Mallinckrodt (Research Grant) and healthcare professional organization activities with the Ameri-can College of Clinical Pharmacy (Treasurer beginning in October). Dr. Jacobi disclosed family relationships with makers of healthcare products (stockholder) and disclosed healthcare professional organization activities with the American College of Clinical Pharmacy (ACCP) (President). Dr. Jordan disclosed healthcare professional organization activities (ACCP member). Dr. McGee disclosed family relationships with makers of health-care products (Pfizer, healthcare professional organization activities with AAHPM (policy committee) and CHEST (membership committee). Dr. Nix disclosed other healthcare professional organization activities with the American College of Ostropathic Surgery committees 1 (in-service exam committee). Dr. Patterson disclosed family relationships with makers of healthcare products (he is an employee of the University of Nebraska Medical Center) and disclosed non-governmental research grant fund-ing (Co-PI for a Surviving Sepsis in Resource Limited Environment Grant from European Society of Intensive Care Medicine and Hellman Founda-tion). Dr. Sands disclosed family relationships with makers of healthcare products, for-profit of healthcare services/products, and with providers of

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient

Michael J. Murray1; Heidi DeBlock2; Brian Erstad3; Anthony Gray4; Judi Jacobi5; Che Jordan6; William McGee7; Claire McManus8; Maureen Meade9; Sean Nix10; Andrew Patterson11; M. Karen Sands12; Richard Pino13; Ann Tescher14; Richard Arbour15; Bram Rochwerg16; Catherine Friederich Murray17; Sangeeta Mehta18

Neuromuscular Blockade in the 21st CenturyManagement of the Critically Ill PatientJulian deBacker, MSc; Nicholas Hart, PhD; and Eddy Fan, MD, PhD

Neuromuscular blockings agents (NMBAs) have a controversial role in the ventilatory and

medical management of critical illness. The clinical concern surrounding NMBA-induced com-

plications stems from evidence presented in the 2002 clinical practice guidelines, but new

evidence from subsequent randomized trials and studies provides a more optimistic outlook

about the application of NMBAs in the ICU. Furthermore, changes in the delivery of critical care,

such as protocolized care pathways, minimizing or interrupting sedation, increased monitoring

techniques, and overall improvements in reducing immobility, have created a modern, 21st

century ICU environment whereby NMBAs may be administered safely. In this article we start

with a review of the mechanism of action, side effects, and pharmacology of commonly used

NMBAs. We then address the rationale for NMBA use for an expanding number of indications

(endotracheal intubation, acute respiratory distress syndrome, status asthmaticus, increased

intracranial and intra-abdominal pressure, and therapeutic hypothermia after cardiac arrest),

with an emphasis on NMBA use in facilitating lung-protective ventilation for respiratory failure.

We end with an appraisal over the importance of monitoring depth of paralysis and the concerns

of complications, such as prolonged skeletal muscle weakness. In the context of adequate

sedation and analgesia, monitored NMBA use (continuous or bolus administration) can be

considered for the small number of clinical indications in critically ill patients for which evidence

currently exists. CHEST 2017; 151(3):697-706

KEY WORDS: airway management; critical care; intensive care units; mechanical ventilation;neuromuscular blocking agents

Neuromuscular blockade, as an adjuvanttherapy in the ventilatory and medicalmanagement of common critical illnesses,has an important but increasinglycontroversial role in the delivery of 21stcentury care in the modern ICU. Clinicalpractice guidelines published in 2002cautioned against the use of neuromuscularblocking agents (NMBAs), suggesting they

only be used when “all other means havebeen tried without success.”1 However, theevidence used in developing the guidelineswas largely observational and, in light ofevidence from more recent prospective andrandomized controlled trials (RCTs), anoptimistic outlook exists for NMBA use inthe ICU. Using the latest evidence, thisreview summarizes the different NMBAs,

ABBREVIATIONS: ACh = acetylcholine; AChR = acetylcholine receptor;CBF = cerebral blood flow; CPP = cerebral perfusion pressure; ICP =intracranial pressure; ICUAW = ICU-acquired weakness; MAP = meanarterial pressure; nAChR = nicotinic acetylcholine receptor; NMBA =neuromuscular blocking agent; RCT = randomized controlled trial;TOF = train-of-fourAFFILIATIONS: From the Cleveland Clinic Lerner College of Medicine(Mr deBacker), Cleveland, OH; the Lane Fox Respiratory Service (DrHart), St. Thomas’ Hospital, Guy’s & St. Thomas’ NHS Foundation

Trust, London, UK; and the Interdepartmental Division of CriticalCare Medicine (Mr deBacker and Dr Fan), Toronto, ON, Canada.CORRESPONDENCE TO: Eddy Fan, MD, PhD, Toronto General Hos-pital, 585 University Ave, PMB 11-123, Toronto, ON, Canada M5G2N2; e-mail: eddy.fan@uhn.caCopyright ! 2016 American College of Chest Physicians. Published byElsevier Inc. All rights reserved.DOI: http://dx.doi.org/10.1016/j.chest.2016.10.040

[ Contemporary Reviews in Critical Care Medicine ]

journal.publications.chestnet.org 697

TABLE 1 ] Pharmacokinetic and Pharmacodynamics of Neuromuscular Blocking Agents

Characteristic

Depolarizing Nondepolarizing

Succinylcholine

Aminosteroid Benzylisoquinolinium

Pancuronium Vecuronium Rocuronium Atracurium Cisatracurium Mivacurium

ED95, mg/kg 0.5-0.6 0.07 0.05 0.3 0.2 0.05 0.08

Dose: intubating,mg/kg

0.5-1 (RSI: 1-1.2) 0.1 0.08-0.1 0.6-1 (RSI: 0.9-1.2) 0.4-0.5 0.1-0.2 0.25

Dose: bolus dosesafter intubation

1.0 0.02 0.02 0.1 0.1 0.15-0.2 0.05

Dose: continuousinfusion, mg/kg/min

Not recommended 0.8-1.7 0.8-1.7 8-12 5-20 1-3 5-6

Onset (time to peakeffect)

30-60 s 3-5 min 3-5 min 1-2 min 3-5 min 3-5 min 2-3 min

Duration Ultrashort (5-10 min) Long (60-90min)

Intermediate(20-35 min)

Intermediate(20-35 min)

Intermediate(20-35 min)

Intermediate(20-35 min)

Short (12-20 min)

Metabolism/elimination

Plasmacholinesterasea

Renal > hepatic Renal # hepatic Renal < hepatic Plasma esteraseand Hofmannelimination

Hofmannelimination

Plasmacholinesterasea

Active metabolites None 3-desacetypancuronium

(50% potency)

3-desacetyl-vecuronium

(50%-70% potency)

None Laudanosine(possible CNS

toxicity)

None None

Effect on cardiacmuscarinicreceptorsb

Stimulates Blocks þþ None Blocks þ None None None

Histamine releasec þ None None None þ None þ

Evidence forcritical illnesspolyneuromyopathy

n/a þþþ þþþ þ þ þ n/a

þ ¼ minimal; þþ ¼ moderate; þþþ ¼ marked; ED95, amount of neuromuscular blocking agents required to reduce twitch height by 95%; n/a, not applicable; RSI ¼ rapid sequence induction. (Sources: Murrayet al1; Miller2; Naguib and Lien3; Warr et al4; Greenberg and Vender5; and Price et al6).aPatients with atypical or reduced pseudocholinesterase may experience prolonged neuromuscular blocking agent blockade.bEffect on cardiac muscarinic receptors is equal to an atropine-like effect.cHistamine release may cause hypotension and tachycardia.

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Rev Bras Anestesiol. 2015;65(4):240---243

REVISTABRASILEIRA DEANESTESIOLOGIA Official Publication of the Brazilian Society of Anesthesiology

www.sba.com.br

SCIENTIFIC ARTICLE

Use of sugammadex on burn patients: descriptive study

Eduardo Rodríguez Sánchez M. ∗, Concepción Martínez Torres, Pablo Herrera Calo,Ignacio Jiménez

Anesthesiology and Reanimation, Hospitales Universitarios Virgen del Rocío, Sevilla, Spain

Received 13 August 2014; accepted 8 October 2014Available online 7 June 2015

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

AbstractObjectives: A burn patient is a challenge for any anesthesiologist, undergoing several surgeriesduring 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 thatdiffers from the healthy patient, thus proper monitoring and reversal is crucial. We analyzedsugammadex effectiveness and safety in this population.Materials and methods: It was a prospectively descriptive study, including 4 patients, and allof them were considered major burn patients, who underwent escharotomy with general anes-thesia and neuromuscular relaxation. The main variable was the time for recovery of a TOFhigher 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 administrationof 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 effec-tive and safe in the burn patient. More analytical, comparative studies of larger populationswould be necessary to confirm these data.© 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rightsreserved.

PALAVRAS-CHAVESugammadex;Gama-Ciclodextrinas;Queimaduras;Rocurônio;Bloqueioneuromuscular;Neostigmina

Uso de sugamadex no paciente queimado: estudo descritivo

ResumoObjetivos: O paciente queimado representa um desafio para o anestesiologista, pois submete-se a várias intervencões cirúrgicas durante sua hospitalizacão, necessitando de anestesia gerale relaxamento muscular na maior parte delas. Apresenta sistema respiratório comprometidoe uma resposta aos relaxantes musculares que difere do paciente sadio; portanto, um moni-toramento correto e reversão tornam-se imprescindíveis. Avaliamos a eficácia e seguranca dosugamadex nesta populacão.

∗ Corresponding author.E-mail: edurodriguez87@yahoo.es (E. Rodríguez Sánchez M.).

http://dx.doi.org/10.1016/j.bjane.2014.10.0010104-0014/© 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

CONCLUSIONES

•  LosBNMenelpacientequemadopresentanalteracionesmuldfactoriales

•  Serequiereincrementodedosishasta3vecessuDE95.

•  Laalteracióndelosreceptorespermaneceinclusohasta3años.