Scholarly article on topic 'Clonidine as Pre-Anesthetic Medication in Cataract Extration: Comparison between 100 μg and 200 μg'

Clonidine as Pre-Anesthetic Medication in Cataract Extration: Comparison between 100 μg and 200 μg Academic research paper on "Clinical medicine"

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Brazilian Journal of Anesthesiology
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{"COMPLICATIONS: intraocular pressure" / "PREMEDICATION: clonidine" / "SURGERY / ophthalmologic: cataract extration" / "CIRURGIA / oftálmica: facectomia" / "COMPLICAÇÕES: pressão intraocular" / "MEDICAÇÃO PRÉ-ANÉSTÉSICA: clonidin"}

Abstract of research paper on Clinical medicine, author of scientific article — José Roquennedy Souza Cruz, Denise Ferreira Barroso de Melo Cruz, Bruno Castelo Branco, Ana Ellen de Queiroz Santiago, José Luiz Gomes do Amaral

Summary Background and objectives The objective of the present study was to evaluate the degree of sedation, intraocular pressure, and hemodynamic changes with premedication with low doses of oral clonidine, 100 μg and 200 μg, in outpatient cataract surgeries. Methods This is a randomized, double-blind, clinical study undertaken at the Universidade Federal de São Paulo with 60 patients of both genders, physical status ASA 1 and 2, ages 18 to 80 years. Patients were separated into three groups: placebo, clonidine 100 μg, and clonidine 200 μg. Intraocular pressure, heart rate, and blood pressure besides assessment of sedation were measured before and 90 minutes after the administration of clonidine. Sedation levels were classified according to the Ramsay sedation scale. Results Patients who received placebo and 100 μg of clonidine did not show reduction in heart rate, while a reduction in heart rate was observed in patients who received 200 μg of clonidine, and this difference was statistically significant. Patients who received 200 μg of clonidine also had a reduction in systolic and diastolic blood pressure (p < 0.05). One patient who received 200 μg of clonidine developed severe hypotension, with systolic pressure < 80 mmHg. Patients treated with clonidine had a reduction in intraocular pressure (p < 0.05). Ninety minutes after the oral administration of placebo and 100 μg and 200 μg of clonidine, 25%, 60%, and 80% of the patients respectively were classified as Ramsay 3 or 4. Conclusions Clonidine 100 μg can be indicated as premedication for fasciectomies, being effective in sedation and reduction of intraocular pressure, without adverse effects on blood pressure and heart rate.

Academic research paper on topic "Clonidine as Pre-Anesthetic Medication in Cataract Extration: Comparison between 100 μg and 200 μg"

Rev Bras Anestesio! 2009; 59: 6: 694-703

ARTIGO CIENTÍFICO SCIENTIFIC ARTICLE

Clonidina como Medicaçâo Pré-Anestésica em Facectomias: Comparaçâo entre as Doses de 100 jg e 200 jg *

Clonidine as Pre-Anesthetic Medication in Cataract Extration: Comparison between 100 jg and 200 jg*

José Roquennedy Souza Cruz, TSA 1, Denise Ferreira Barroso de Melo Cruz 2, Bruno Castelo Branco 3, Ana Ellen de Queiroz Santiago, TSA 4, José Luiz Gomes do Amaral, TSA 5

RESUMO

Cruz JRS, Cruz DFBM, Branco BC, Santiago AEQ, Amaral JLG -Clonidina como Medicapao Pré-Anestésica em Facectomias: Comparado entre as Doses de 100 |jg e 200 |jg.

JUSTIFICATIVA E OBJETIVOS: Avaliar a sedapao, a pressao intraocular e as alterapoes hemodinamicas com o uso de doses baixas de clonidina, 100 jg e 200 jg por via oral, como medica-pao pré-anestésica para operapoes de catarata em regime ambulatorial.

MÉTODO: O trabalho foi realizado pela Universidade Federal de Sao Paulo, sendo um estudo clínico aleatorio e duplamente enco-berto em 60 pacientes, de ambos os sexos, estado físico ASA 1 e 2, com idade mínima de 18 anos e máxima de 80 anos. Os pacientes foram divididos em tres grupos: placebo, clonidina 100 jg e 200 jg. As medidas de pressao intraocular, frequencia cardíaca e pressao arterial, além da avaliapao de sedapao, foram feitas antes e após 90 minutos da administrapao da clonidina. Os níveis de sedapao foram classificados de acordo com a escala de sedapao de Ramsay.

RESULTADOS: Pacientes que receberam placebo e 100 jg de clonidina nao apresentaram redupao da frequencia cardíaca com diferenpa estatística significativa, enquanto os que receberam 200 jg de clonidina, sim. Os que receberam clonidina na dose de 200 jg apresentaram redupao na pressao arterial sistólica e diastólica (p < 0,05). Um paciente que utilizou 200 jg de clonidina desenvol-veu hipotensao arterial grave com pressao sistólica < 80 mmHg.

* Recebido da (Received from) Universidade Federal de Sao Paulo (UNIFESP), SP

1. Médico Anestesiologista da Universidade Federal de Sergipe; Médico Intensivista pela Associapao Brasileira de Medicina Intensiva

2. Oftalmologista do Instituto de Olhos de Sergipe - Ocular Day Hospital; Mestrado MBA em Oftalmología pela UNIFESP; Título de Especialista em Oftalmología pelo Conselho Brasileiro de Oftalmologia

3. Professor Substituto de Oftalmologia da Universidade Federal da Bahia; Doutor em Medicina pela UNIFESP; Mestrado MBA em Oftalmologia pela UNIFESP; Título de Especialista em Oftalmologia pelo Conselho Brasileiro de Oftalmologia

4. Professora Assistente de Anestesiologia da Universidade Federal de Rondónia

5. Professor Titular de Anestesiologia da UNIFESP; Especialista em Medicina Intensiva pela AMIB; Doutor e Mestre em Medicina pela Escola Paulista de Medicina; Professor Livre-Docente pela Faculdade de Medicina de Botucatu-UNESP

Apresentado (Submitted) em 11 de fevereiro de 2009 Aceito (Accepted) para publicapao em 21 de julho de 2009

Enderepo para correspondencia (Correspondence to):

Dr. José Roquennedy Souza Cruz

Av. Sílvio Teixeira, 10 CC Brava, Barcelona 303

49025-100 Aracaju, SE

E-mail: roquennedy@uol.com.br

Os pacientes tratados com clonidina apresentaram redupao da pressao intraocular (p < 0,05). Quanto á sedapao, 90 minutos após a administrapao de placebo e clonidina 100 jg e 200 jg por via oral, 25%, 60% e 80% dos pacientes encontravam-se, respectivamente, em Ramsay 3 ou 4.

CONCLUSÓES: A dose de 100 jg de clonidina pode ser indicada como medicapao pré-anestésica para facectomia, possuindo efeito na sedapao, diminuipao da pressao intraocular e ausencia de efei-tos adversos na pressao arterial sistemica e frequencia cardíaca.

Unitermos: CIRURGIA, oftálmica: facectomia; COMPLICAQÓES: pressao intraocular; MEDICAQÁO PRÉ-ANÉSTÉSICA: clonidina

SUMMARY

Cruz JRS, Cruz DFBM, Branco BC, Santiago AEQ, Amaral JLG -Clonidine as Pre-Anesthetic Medication in Cataract Extration: Comparison between 100 |jg and 200 |jg.

BACKGROUND AND OBJECTIVES: The objective of the present study was to evaluate the degree of sedation, intraocular pressure, and hemodynamic changes with premedication with low doses of oral clonidine, 100 jg and 200 jg, in outpatient cataract surgeries.

METHODS: This is a randomized, double-blind, clinical study undertaken at the Universidade Federal de Sâo Paulo with 60 patients of both genders, physical status ASA 1 and 2, ages 18 to 80 years. Patients were separated into three groups: placebo, clonidine 100 jg, and clonidine 200 jg. Intraocular pressure, heart rate, and blood pressure besides assessment of sedation were measured before and 90 minutes after the administration of clonidine. Sedation levels were classified according to the Ramsay sedation scale.

RESULTS: Patients who received placebo and 100 jg of clonidine did not show reduction in heart rate, while a reduction in heart rate was observed in patients who received 200 jg of clonidine, and this difference was statistically significant. Patients who received 200 jg of clonidine also had a reduction in systolic and diastolic blood pressure (p < 0.05). One patient who received 200 jg of clonidine developed severe hypotension, with systolic pressure < 80 mmHg. Patients treated with clonidine had a reduction in intraocular pressure (p < 0.05). Ninety minutes after the oral administration of placebo and 100 jjg and 200 jjg of clonidine, 25%, 60%, and 80% of the patients respectively were classified as Ramsay 3 or 4.

CONCLUSIONS: Clonidine 100 jg can be indicated as premedication for fasciectomies, being effective in sedation and reduction of intraocular pressure, without adverse effects on blood pressure and heart rate.

Keywords: COMPLICATIONS: intraocular pressure; PREMEDICATION: clonidine; SURGERY, ophthalmologic: cataract extration.

INTRODUQÁO

A medicagao pré-anestésica tem como objetivos: redugao da ansiedade, sedagao, amnésia, analgesia, redugao de secre-gao das vias aéreas, prevengao de respostas a reflexos autonómicos, redugao do volume do conteúdo gástrico e/ou aumento do pH, efeito antiemético, facilitagao da indugao anestésica, redugao das necessidades de anestésicos, profilaxia de reagoes alérgicas e prevengao de eventos isquémicos miocárdicos 1-5. Alguns desses objetivos, como alivio da ansiedade e sedagao, aplicam-se a quase todos os pacientes, enquanto outros apenas ocasionalmente 6. A clonidina é o prototipo dos a2-agonistas adrenérgicos. Tem efeito anti-hipertensivo, sedativo, inibidor de hiperatividade adrenérgica, bem como potente propriedade analgésica, antissialogoga e de diminuigao da pressao intraocular 78. A clonidina como medicagao pré-anestésica reduz a incidén-cia de isquemia miocárdica intraoperatória 19,10, melhora o controle metabólico em pacientes diabéticos 11,12, reduz a in-cidéncia de náuseas e vómitos no pós-operatório 13,14 e reduz ou abole os tremores no pós-operatório 915. O efeito da clonidina nas variáveis hemodinámicas é controverso. Em operagoes de catarata, a clonidina em dose de 150 jg pode apresentar efeitos hemodinámicos indesejáveis 78,16. Mas há também estabilidade hemodinámica com essa dose, mesmo em populagao geriátrica 17. Em doses mais altas, acrescen-ta-se ainda diminuigao excessiva da pressao intraocular 17. Os resultados dos trabalhos publicados até o momento nao sao suficientes para definir a melhor estratégia na condu-gao da anestesia para tratamento cirúrgico de catarata 1819. A maioria dos trabalhos com clonidina como medicagao pré-anestésica em oftalmologia comparam doses de 150 a 300 jg. Com a hipótese de se obterem os efeitos desejáveis de sedagao e diminuigao da pressao intraocular, com estabili-dade hemodinámica, utilizando doses menores de clonidina, este estudo avaliou a sedagao, a pressao intraocular e as alteragoes hemodinámicas associadas ao uso da clonidina nas doses de 100 jg e 200 jg por via oral como medicagao pré-anestésica para operagoes de catarata em regime ambulatorial, em comparagao ao placebo.

MÉTODO

O estudo foi aprovado pelo Comité de Ética em Pesquisa da Escola Paulista de Medicina, Universidade Federal de Sao Paulo. Foi realizado estudo clínico aleatório e duplamente encoberto em 60 (sessenta) pacientes, de ambos os sexos, estado físico ASA I e II, com idade minima de 18 anos e máxima de 80 anos, submetidos a facectomia extracapsular, utilizando ou nao o facoemulsificador. Todos os pacientes que participaram do estudo assinaram termo de consentimiento esclarecido após receberem informagoes sobre os objetivos e riscos do uso da clonidina por via oral. Os dados foram colhidos pelo mesmo médico anestesiologista e of-talmologista.

Foram excluidos do estudo, pacientes com infarto agudo do miocárdio nos 12 meses anteriores a operagao, dor precordial tipo angina, hipertensao arterial descontrolada, uveite, glaucoma, intervengao cirúrgica ocular prévia ou uso crónico de medicagoes tópicas. Foram anotados: peso, altura, estado físico ASA, doengas associadas e procedimento cirúrgico a ser realizado.

A distribuigao aleatória foi feita utilizando-se 60 envelopes em branco, fechados previamente, identificando a medica-gao pré-anestésica. Existiam nesses envelopes 20 cartoes para cada um dos grupos: placebo, clonidina 100 |jg e clonidina 200 jg. A pessoa que abria o envelope e adminis-trava nao comunicava ao paciente ou aos médicos o conteúdo administrado: grupo 1 - placebo; grupo 2 - clonidina 100 jg; grupo 3 - clonidina 200 jg.

A dilatagao pupilar foi realizada com fenilefrina 10%, 2 gotas e tropicamida 1%, 2 gotas em todos os pacientes após a verificagao da pressao arterial e da frequéncia cardiaca. A pressao intraocular foi medida nos dois olhos com o tonómetro de aplanagao de Perkins.

Após 90 minutos da administragao da clonidina por via oral, eram feitas novas medidas da pressao intraocular, frequéncia cardiaca e pressao arterial. Em seguida, procedia-se ao bloqueio peribulbar. Após instilagao de proximetacaina e antissepsia com iodopovidona tópica, a anestesia peribulbar foi realizada pela técnica de duas pungoes (superior e inferior) com agulha 30 * 7 mm. Após 15 minutos da reali-zagao do bloqueio e cerca de 105 minutos após a adminis-tragao da clonidina, era feita nova avaliagao da sedagao. Os niveis de sedagao foram estudados antes e após a administragao de clonidina por via oral e durante o procedi-mento cirúrgico, de acordo com a escala de sedagao de Ramsay 20: 1 - paciente ansioso; 2 - calmo, acordado; 3 -sonolento, mas abre os olhos quando chamado; 4 - dormin-do e responde somente a estimulos verbais vigorosos; 5 -dormindo e responde a estimulo doloroso de compressao da glabela; 6 - nao responde a estimulo doloroso. Os resultados foram analisados como média ± desvio-pa-drao (DP). A comparagao entre os grupos quanto a pressao intraocular, frequéncia cardiaca e pressao arterial foi realizada pelo teste paramétrico t de Student. Dados ordinais, como sedagao, foram analisados pelo teste de Kruskall-Wallis. Os dados obtidos foram considerados significativos quando o valor do p foi inferior a 0,05.

RESULTADOS

Os grupos nao apresentaram diferenga estatistica significativa quanto ao sexo, idade, altura e peso (Tabela I). Foram avaliados 23 pacientes do sexo feminino (38%) e 37 do sexo masculino (62%). A média de peso dos pacientes dos grupos 1, 2 e 3 foi de 63,7 ± 9,5; 69,5 ± 9,3; 67,9 ± 12, respectivamente.

Desses pacientes, 36 (60%) eram higidos e 24 (40%) tinham doengas sistémicas associadas sendo classificados como

ASA I e II, respectivamente. A técnica cirúrgica mais realizada foi a de facoemulsificagao (73%). Hipertensao arterial sistémica (11) e diabetes mellitus (5) foram as doengas mais comumente encontradas. Foi relatado ainda um caso de artrite reumatoide, um caso de epilepsia e outro de rinite alérgica.

Os pacientes que receberam placebo e 1GG |jg de clonidina näo apresentaram reduçäo significativa da frequéncia cardiaca, enquanto os pacientes que receberam 2GG jg apresentaram reduçäo significativa na frequéncia cardiaca (Tabela II).

Tabela I - Dados Demográficos

Grupo 1 Grupo 2 Grupo 3

Masculino 12 (6G%) 13 (65%) 12 (6G%)

Feminino 8 (4G%) 7 (35%) 8 (4G%)

Idade (anos) * 64 i 1G,5 61,5 i 16,4 61,8 i 2,6

Peso (kg) * 63,7 i 9,5 69,5 i 9,3 67,9 i 12

Altura (cm) * 162 i7,4 163 i 8,6 162 i 6,3

Valores expressos em Média i DP

Grupo 1 - placebo; Grupo 2 - clonidina 1GG jg; Grupo 3 - clonidina 2GG jg

Tabela II - Influéncia da Clonidina Usada Como Medicaçäo Pré-Anestésica

Controle

Após 9G min

Frequéncia Cardiaca

Grupo 1 77,25 i 11,2

Grupo 2 75,6 i 9,3

Grupo 3 79,75 i 16,95 Pressäo arterial sistólica

Grupo 1 14G i 19

Grupo 2 132 i 16

Grupo 3 14G i 19

Pressäo arterial diastólica

Grupo 1 84 i 9

Grupo 2 83 i 8,6

Grupo 3 87 i 1G

Pressäo intraocular sem dilatapäo pupilar

Grupo 1 12,5 i 3

Grupo 2 12,3 i 2,8

Grupo 3 14,6 i 3,8

Pressäo intraocular com dilatapäo pupilar por fenilefrina e tropicamida

Grupo 1 11,9 i 3

Grupo 2 12,3 i 2,6

Grupo 3 14,6 i 3,9

76.2 i 11,8 72,35 i 12,7 68,35 i 1G,3

142 i 17 13G i 17 126 i 19

85 i 11 81 i 8,5 76,5 i 13

12.3 i 2,8 1G,2 i 2,4 1G,9 i 3,3

1G,9 i 3 1G,6 i 2,5 11 i 5,6

G,55 G,16 G,GG4 *

G,57 G,88 G,GG6 *

G,82 G,37 G,GGG6 **

G,1 G,GG1 * G.GGG2 **

G,G7 G,GG3 * G,GGG2 **

Valores expressos em Média i DP

Grupo 1 - placebo; Grupo 2 - clonidina 1GG jg; Grupo 3 - clonidina 2GG jg

* Valor de p < G,G5; ** valor de p < G,GG1

CLONIDINA COMO MEDICAÇÂO PRÉ-ANESTÉSICA EM FACECTOMIAS: COMPARAÇÂO ENTRE AS DOSES DE 100 jig E 200 |jg Tabela III - Avaliaçâo da Sedaçâo Induzida pela Clonidina pela Escala de Sedaçâo de Ramsay

Tempo Ramsay Grupo 1 Grupo 2 Grupo Э p

M0 1 - - -

2 19 (95%) 20 (100%) 20 (100%) 0,95

Э 1 (5%) - -

4 - - -

M1 1 - - -

2 15 (75%) 8 (40%) 4 (20%)

Э 5 (25%) 10 (50%) 10 (50%) 0,0001 **

4 - 2 (10%) б (Э0%)

M2 1 - - -

2 9 (45%) б (Э0%) 1 (5%) 0,004 *

Э 10 (50%) 9 (45%) 11 (55%)

4 1 (5%) б (25%) 8 (40%)

p 0,015 * 0,0001 ** 0,0001 **

M0 - controle; M1 - 90 min após clonidina; M2 - 10б min após clonidina * Valor de p < 0,0б; ** valor de p < 0,001

A Tabela II apresenta as médias de pressöes sistólicas nos grupos. Os pacientes que receberam clonidina na dose de 200 ¡g (grupo Э) mostraram reduçâo na pressao arterial sistólica com diferença estatística significativa. Também nos pacientes deste grupo houve reduçâo significativa na pressâo arterial diastólica (Tabela II). Um paciente nesse grupo desenvolveu hipotensâo arterial grave com pressâo sistólica menor que 80 mm Hg, tratada com infu-sâo rápida de Ringer com lactato.

Os pacientes que receberam clonidina e dilataçâo pupilar apresentaram reduçâo significativa da pressâo intraocular (Tabela II). No grupo placebo, houve tendência à reduçâo da pressâo intraocular, mas sem diferença estatística significativa.

Os pacientes que receberam clonidina e nâo foram submeti-dos à dilataçâo pupilar apresentaram reduçâo significativa da pressâo intraocular. No grupo placebo, houve tendência à reduçâo da pressâo intraocular, mas que nâo alcançou diferença estatística significativa (Tabela II). Quanto ao nível de sedaçâo obtido, após 90 minutos da ad-ministraçâo da clonidina por via oral б0% dos pacientes do grupo 2 e 80% do grupo Э estavam em Ramsay de Э ou 4 contra 250/o do grupo 1. Após a realizaçâo do bloqueio peribulbar com bupivacaína, 55%, 70% e 95% dos grupos 1, 2 e Э encontravam-se em Ramsay de Э ou 4 (Tabela III).

DISCUSSÄO

As doses de clonidina utilizadas neste estudo clínico controlado encoberto acrescentam resultados ainda nâo testados com a dose de 100 ¡g de clonidina por via oral como medi-caçâo pré-anestésica, em comparaçâo à de 200 ¡g. O presente estudo demonstrou que é possível realizar sedaçâo

e obter diminuigäo da pressao intraocular sem ter alterares hemodinámicas significativas com 100 |jg. No estudo, 60% dos pacientes apresentavam estado físico ASA I e 40% ASA II. Hamilton e col., em 12.000 procedimientos consecutivos de facectomia com implantagäo de lente intraocular, detectaram predomináncia de pacientes ASA 2 e 3. Schein e col. avaliando cerca de 20.000 pacientes com catarata também observaram que a maioria do grupo estava no estado físico ASA 2, porém neste estudo houve número menor de pacientes com comorbidades 21-23. Como medicagäo pré-anestésica em pacientes com dilata-gäo pupilar com tropicamida e fenilefrina a dose de 100 jg e 200 jg de clonidina por via oral causou redugäo de 13 e 24% da pressäo intraocular, respectivamente. Utilizando clonidina de 100 e 200 jg por via oral, a redugäo da pressäo intraocular nos pacientes sem dilatagäo pupilar foi de 17 e 25%, respectivamente. A avaliagäo do olho contralateral demonstrou que a redugäo da pressäo intraocular näo foi secundária ao uso dos colirios de tropicamida e fenilefrina. Na literatura consultada, näo foi encontrada comparagäo entre as doses baixas usadas neste estudo. Ghignone e col. re-lataram redugäo de 35% na pressäo intraocular (PIO) entre 90 e 120 min após dose oral de 5 jg.kg-1 de pre-medicagäo com clonidina, sendo sustentada por pelo menos seis horas 17. Filos e col. encontraram uma diminuigäo ainda maior na PIO (47,8%) com uma dose oral semelhante, enquanto obtive-ram uma redugäo de 32,1% com a dose de 150 jg (2 a 2,5 jg.kg-1), com diferenga estatística significativa em relagäo com controle 8 Embora a redugäo na PIO seja um efeito de-sejado na extragäo de catarata, a redugäo muito grande pode resultar em dificuldade técnica para os cirurgiöes. Filos e col., com a dose de 4 a 4,5 jg.kg-1 de clonidina (300 jg) por via oral como medicagäo pré-anestésica, encontraram

dificuldade cirúrgica em 9 de 2G pacientes (reduçäo de 47,8 i 17,2%.), enquanto näo houve qualquer reclair^äo dos cirurgiöes nos outros dois grupos: dose baixa de 15G jg e placebo (p < G,G1), questionando-se aquela dose para me-dicaçäo pré-anestésica 8. No presente estudo, näo houve relato por parte dos cirurgiöes de dificuldade técnica. A avaliaçäo de medicaçäo pré-anestésica deve considerar, obviamente, efeitos desejados e incidéncia de complica-çöes 21 2425. A dose de 15G jg por via oral, por exemplo, foi considerada dose baixa, com alguns autores relatando al-te^öes hemodinâmicas associadas 7,8,16 e outros näo 17. O efeito da clonidina nas variáveis hemodinâmicas é con-troverso, com alguns autores sugerindo que näo há altera-çöes hemodinâmicas importantes em pacientes jovens e higidos, enquanto outros relatam diminu^äo da pressäo arterial sistémica e bradicardia, mesmo nesse grupo. Outros, ainda, relatam maior estabilidade hemodinâmica em compa^äo a pacientes sem uso de clonidina pré-opera-tória. No presente estudo, näo houve casos de bradicardia ou hipotensäo arterial nos pacientes tratados com 1GG jg de clonidina. Em contrapartida, houve um caso de hipoten-säo arterial grave (PAS menor que 8G mm Hg) no grupo de pacientes que recebeu a dose de 2GG jg. Filos e col., utilizando dose de 3GG jg de clonidina por via oral como medi-caçäo pré-anestésica, relataram 5G% de bradicardia e 4G% de hipotensäo arterial em pacientes idosos submetidos a tratamento cirúrgico de catarata. Com a dose de 15G jg, en-controu Ю% de bradicardia, havendo diferença estatistica significativa entre os valores de bradicardia no grupo de dose alta e no de placebo. Em re^äo à pressäo arterial, houve diferença significativa entre os dois grupos de clonidina e placebo, com diminu^äo das pressöes arteriais sistólica, diastólica e média. Foi encontrada diferença estatistica significativa também entre os dois grupos de clonidina (p < G,GG1) 8. Ghignone e col. registraram 35% de casos de bradicardia com a dose de 3GG jg e näo encontraram com-plicaçöes com a dose de 15G jg em pacientes geriátricos submetidos a ope^öes oftálmicas 17. Stocche e col., estu-dando 6G pacientes submetidos ao tratamento cirúrgico de catarata com bloqueio peribulbar e dose de 15G jg de clonidina como medicaçäo pré-anestésica em pacientes idosos, encontraram um caso de bradicardia (FC = 39 bpm) e nenhum no grupo controle 16. Outro estudo, com a clonidina por via oral como pré-medicaçäo na dose de 3GG jg, encontrou vários casos de hipotensäo arterial no periodo intra e pós-operatório 26. Já outro com a clonidina por via oral na dose de 3GG jg como medicaçäo pré-anestésica näo encontrou alte^äo hemodinâmica significante em re^äo ao grupo placebo 27.

Ferreira e col., utilizando clonidina 1GG jg via oral como pré-medicaçäo em ope^öes oftálmicas em 3G pacientes, encontraram 33% de bradicardia e 3G% de hipotensäo arterial em pacientes submetidos à anestesia geral, sendo que nos pacientes submetidos à anestesia locorregional näo houve bradicardia nem hipotensäo arterial 28. Stocche e col. obtive-

ram 6G% de pacientes "calmos ou dormindo" quando tratados com clonidina 15G jg via oral após 3G minutos como medicaçäo pré-anestésica 16. Esses resultados säo seme-lhantes aos do presente estudo, porém neste com a dose de 1GG jg de clonidina.

As operaçöes intraoculares com anestesia regional deman-dam um paciente calmo, quieto e cooperativo 19,21,24,25,29. Noventa minutos após utilizar-se a clonidina nas doses de 1GG e 2GG jg, 6G% e 8G% dos pacientes estavam sedados em Ramsay 3 e 4, respectivamente, enquanto 25% dos que uti-lizaram placebo apresentavam-se naqueles niveis de se-daçäo. Nenhum paciente necessitou de complementaçäo na sedaçäo, teve ag^äo ou mesmo sedaçäo excessiva. Concluindo, a clonidina na dose de 1GG jg pode ser indicada como medicaçäo pré-anestésica para facectomia por seu efeito na sedaçäo, na diminu^äo da pressäo intraocular e pela auséncia de efeitos adversos na pressäo arterial sistémica e na frequéncia cardiaca.

Clonidine as Pre-Anesthetic Medication in Cataract Extration: Comparison between 100 pg and 200 pg

José Roquennedy Souza Cruz, TSA, M.D., Denise Ferreira Barroso de Melo Cruz, M.D., Bruno Castelo Branco, M.D., Ana Ellen de Queiroz Santiago, TSA, M.D., José Luiz Gomes do Amaral, TSA, M.D.

INTRODUCTION

The objectives of premedication include: reduction of anxiety, sedation, amnesia, analgesia, reduction of airways secretion, prevention of the response to autonomous reflexes, reduction of the gastric volume and/or increase in pH, antiemetic action, facilitate anesthetic induction, reduction in the need of anesthetics, prophylaxis of allergic reactions, and prevention of myocardial ischemia1-5. Some of those objectives such as anxiety relief and sedation apply to virtually all patients while others only occasionally6. Clonidine is the prototype of a2-adrenergic agonists. It has antihypertensive and sedative properties, inhibits adrenergic hyperactivity, it has potent analgesic properties, antisiala-gogue, and decreases intraocular pressure7,8. Premedication with clonidine reduces the incidence of intraoperative myocardial ischemia1910, improves metabolic control in diabetics1112, reduces the incidence of postoperative nausea and vomiting13,14, and reduces or abolishes postoperative tremors9,15. The effects of clonidine on hemodynamic parameters are controversial. In cataract surgeries, 150 |jg of clonidine can have undesirable effects7816. But this dose is also associated with hemodynamic stability, even in the geriatric population17. Higher doses are associated with excessive reduction in intraocular pressure17.

The results of studies published so far are not enough to define the best strategy when conducting anesthesia for the surgical treatment of cataracts18,19. The majority of the studies on premedication with clonidine in ophthalmologic surgeries compared doses of 150 and 300 |jg. With the hypothesis of obtaining the desirable effects of sedation and reduction in intraocular pressure with hemodynamic stability using lower doses of clonidine, this study evaluated sedation, intraocular pressure, and hemodynamic changes associated with premedication with 100 jg and 200 jg of oral clonidine in outpatient cataract surgeries and compared them with placebo.

METHODS

This study was approved by the Ethics on Research Committee of the Escola Paulista de Medicina, Universidade Federal de Sao Paulo. A randomized double-blind clinical study was conducted with 60 patients of both genders, physical status ASA I and II, 18 to 80 years old, undergoing extracapsular fasciectomy with or without phacoemulsifier. All patients signed an informed consent after being informed of the objectives and risks of oral clonidine. Data were gathered by the same anesthesiologist and ophthalmologist. Patients with acute myocardial infarction during the 12-month period before surgery, angina, uncontrolled hypertension, uveitis, glaucoma prior ophthalmologic surgery or chronic use of topical drugs were excluded. Weight, height, physical status ASA, associated diseases, and surgical procedure performed were recorded.

Sixty white envelopes previously sealed identifying the premedication were used for randomization. Those envelopes contained 20 cards for each group: placebo, 100 jg of clonidine, and 200 jg of clonidine. The person who opened the envelope and administered the premedication did not tell the patients and physicians which drug was administered: group 1 - placebo; group 2 - clonidine 100 jg; and group 3 -clonidine 200 jg.

Two drops of 10% phenylephrine and 2 drops of 1% tro-picamide were used to dilate the pupils of all patients after

determination of the blood pressure and heart rate. Intraocular pressure was measured in both eyes with the Perkins applanation tonometer.

Ninety minutes after the administration of oral clonidine, intraocular pressure, heart rate, and blood pressure were measured again. This was followed by the peribulbar block. After instillation of proximetacaine and antisepsis with topical povidone-iodine, peribulbar block with the two-puncture technique (superior and inferior) with a 30 x 7 mm needle was performed. Fifteen minutes after the blockade, and approximately 105 minutes after the administration of clonidine, sedation was evaluated once more. The levels of sedation were evaluated before and after the oral administration of clonidine, according to the Ramsay sedation scale20: 1 - anxious; 2 - calm, awake; 3 - sleepy, but opens eyes to verbal commands; 4 - sleeping, only answers to vigorous verbal commands; 5 - sleeping, responding to painful stimulus of glabellar compression; and 6 - absence of answer to painful stimuli. Results were analyzed as mean ± standard deviation (SD). The parametric Student t test was used to compare intraocular pressure, heart rate, and blood pressure among the groups. The Kruskall-Wallis test was used for ordinal data, such as sedation. Data were considered significant when p < 0.05.

RESULTS

Significant statistical differences in gender, age, height, and weight were not observed among the groups (Table I). Twenty-three females (38%) and 37 males (62%) were evaluated. Patients in groups 1, 2, and 3 had a mean weight of 63.7 ± 9.5, 69.5 ± 9.3, and 67.9 ± 12 kg, respectively. Thirty-six (60%) of those patients were healthy and 24 (40%) had associated diseases, being classified as ASA I and II, respectively. Phacoemulsification was the technique used more often (73%).

Hypertension (11) and diabetes mellitus (5) were the disorders observed more often. One case of rheumatoid arthritis, one of epilepsy, and one of allergic rhinitis were also observed.

Table I - Demographic Data

Group 1 Group 2 Group 3

Gender

Male 12 (60%) 13 (65%) 12 (60%)

Female 8 (40%) 7 (35%) 8 (40%)

Age (years) * 64 ± 10,5 61.5 ± 16.4 61.8 ± 2.6

Weight (kg) * 63.7 ± 9.5 69.5 ± 9.3 67.9 ± 12

Height (cm) * 162 ±7.4 163 ± 8.6 162 ± 6.3

Data expressed as Mean ± SD

Group 1 - placebo; Group 2 - Clonidine, 100 |jg; Group 3 - Clonidine, 200 |jg

Patients who received placebo and 100 pg of clonidine did not have significant reductions in heart rate, while patients who received 200 pg had significant reduction in heart rate (Table II).

Table II shows the mean systolic blood pressure in the study groups. A statistically significant reduction in systolic blood pressure was observed in patients who received 200 pg of clonidine (group 3).

A significant reduction in diastolic blood pressure was also observed in patients in group 3 (200 pg of clonidine) (Table II). One patient in this group developed severe hypotension with systolic blood pressure lower than 80 mmHg treated with rapid infusion of Ringer's lactate. Patients who received clonidine and pupillary dilation had a significant reduction in intraocular pressure (Table II). In

the placebo group, a tendency for the reduction of intraocular pressure was observed, but it was not statistically significant.

A significant reduction in intraocular pressure was observed in patients who received clonidine but not pupillary dilation. In the placebo group, a tendency for the reduction of the intraocular pressure was observed, but it was not statistically significant (Table II).

As for the level of sedation, 90 minutes after the oral administration of clonidine, 60% of the patients in groups 2 and 80% of the patients in group 3 presented Ramsay 3 or 4 versus 25% of the patients in groups 1. After peribulbar block with bupivacaine 55%, 70%, and 95% of the patients in groups 1, 2, and 3 respectively presented Ramsay 3 or 4 (Table III).

Table II - Influence of Premedication with Clonidine

Control

After 90 min

Heart rate Group 1 Group 2 Group 3

Systolic blood pressure Group 1 Group 2 Group 3

Diastolic blood pressure Group 1 Group 2 Group 3

77.25 ± 11.2 75.6 ± 9.3 79.75 ± 16.95

140 ± 19 132 ± 16 140 ± 19

84 ± 9 83 ± 8,6 87 ± 10

Intraocular pressure without pupillary dilation

Group 1 12.5 ± 3

Group 2 12.3 ± 2.8

Group 3 14.6 ± 3.8

Intraocular pressure with phenylephrine and tropicamide-induced

Group 1 11.9 ± 3

Group 2 12.3 ± 2.6

Group 3 14.6 ± 3.9

76.2 ± 11.8 72.35 ± 12.7 68.35 ± 10.3

142 ± 17 130 ± 17 126 ± 19

85 ± 11 81 ± 8,5

76.5 ± 13

12.3 ± 2.8 10.2 ± 2.4 10.9 ± 3.3

pupillary dilation 10.9 ± 3

10.6 ± 2.5 11 ± 5.6

0.55 0.16 0.004 *

0.57 0.88 0.006 *

0.82 0.37 0.0006 **

0.1 0.001 * 0.0002 **

0.07 0.003 * 0.0002 **

Data expressed as Mean ± SD

Group 1 - placebo; Group 2 - clonidine, 100 |jg; Group 3 - clonidine, 200 |jg

* p < 0.05; ** p < 0.001

Table III - Evaluation of Clonidine-Induced Sedation According to the Ramsay Sedation Scale

Time Ramsay Group 1 Group 2 Group 3 p

M0 1 - - -

2 19 (95%) 20 (100%) 20 (100%) 0,95

3 1 (5%) - -

4 - - -

M1 1 - - -

2 15 (75%) 8 (40%) 4 (20%)

3 5 (25%) 10 (50%) 10 (50%) 0,0001 **

4 - 2 (10%) 6 (30%)

M2 1 - - -

2 9 (45%) 6 (30%) 1 (5%) 0,004 *

3 10 (50%) 9 (45%) 11 (55%)

4 1 (5%) 5 (25%) 8 (40%)

p 0.015 * 0.0001 ** 0.0001 **

M0 - control; M, - 90 min after clonidine; M2 - 105 min after clonidine * [3 < 0.05; ** p < 0.001

DISCUSSION

The doses of clonidine used in the present controlled double-blind clinical study presents results not tested yet on premedication with 100 pg of oral clonidine compared to 200 pg. The present study showed that it is possible to achieve sedation and a reduction in intraocular pressure without significant hemodynamic changes with 100 pg of clonidine. In this study, 60% of the patients were classified as ASA I and 40% ASA II. Hamilton et al. detected a predominance of patients ASA 2 and 3 in 12,000 consecutive fasciectomies with intraocular lens implantation. Schein et al., evaluating 20,000 patients with cataract also observed that the majority was classified as ASA 2, but this study had a lower number of patients with comorbidities21-23.

Premedication with oral clonidine, 100 pg and 200 pg, in patients with pupillary dilation with tropicamide and phenylephrine caused a 13 and 24% reduction in intraocular pressure respectively. Using oral clonidine, 100 pg and 200 pg, a 17 and 25% reduction in intraocular pressure without pupillary dilation, respectively, was observed. Evaluation of the contralateral eye showed that the reduction in intraocular pressure was not secondary to the use of tropicamide and phenylephrine.

Comparisons between low doses of clonidine such as the ones used in this study were not found in the literature. Ghig-none et al. reported a 35% reduction in intraocular pressure (IOP) 90 to 120 minutes after premedication with 5 pg.kg-1 of oral clonidine, which lasted for at least six hours 17. Filos et al. observed an even greater reduction in IOP (47.8%) after similar oral dose, and a 32.1% reduction with 150 pg (2 to 2.5 pg.kg-1) of clonidine, which was significantly different that the control group 8. Although reduction in IOP is a de-

sirable effect in cataract extraction, an exaggerated reduction can result in technical difficulties for the surgeons. Filos et al., using 4 to 4.5 pg.kg-1 of oral clonidine (300 pg) as premedication, met with surgical difficulties in nine out of 20 patients (reduction of 47.8 ± 17.2%), while the surgeons of the other two groups, 150 pg and placebo, did not have any complaints (p < 0.01), raising the question of whether that dose should be used as premedication8. In the present study, the surgeons did not report technical difficulties. Evaluation of premedication should obviously consider undesirable effects and the incidence of complications21,24,25. The oral dose of 150 pg, for example, was considered low, with some authors reporting associated hemodynamic changes7,8,16 while others did not17. The effects of clonidine on hemodynamic parameters is controversial, with some authors suggesting that young and healthy patients do not develop hemodynamic changes, while others reported a reduction in systolic blood pressure and bradycardia in the same group of patients. Others have reported greater hemodynamic stability when compared to patients who were not premedicated with clonidine. In the present study, bradycardia and hypotension were not observed in patients who received 100 pg of clonidine. On the other hand, one case of severe hypotension (SBP < 80 mmHg) was observed in the group of patients premedicated with 200 pg of clonidine. Filos et al, using 300 pg of oral clonidine as premedication, observed and incidence of 50% of bradycardia and 40% of hypotension in elderly patients undergoing surgical treatment of cataracts. With 150 pg they observed a 10% incidence of bradycardia, and a statistically significant difference was observed in the levels of bradycardia between the high dose and placebo groups. As for blood pressure, a significant difference was observed between the two clonidine groups

and the placebo group, with a reduction in systolic and diastolic blood pressure and mean arterial pressure. A statistically significant difference was also observed between the two clonidine groups (p < 0.001)8. Ghignone et al. recorded and incidence of 35% of bradycardia with the dose of 300 |jg, but they did not observe complications with the 150 jg dose in elderly patients undergoing ophthalmologic surgeries17. Stocche et al., studying 60 elderly patients undergoing surgical treatment of cataract with peribulbar block and premedication with 150 jg of clonidine, observed one case of bradycardia (HR = 39 bpm) and none in the control group16. Another study with premedication with 300 jg of oral clonidine observed several cases of intra- and postoperative hypotension26. On the other hand, in another study with 300 jg of oral clonidine as premedication, significant hemodynamic changes were not observed when compared with the placebo group27.

Ferreira et al., in a study with 30 patients, administered 100 jg of clonidine as premedication for ophthalmologic surgeries and observed 33% of bradycardia and 30% of hypotension in patients who underwent general anesthesia, but patients who underwent regional blocks did not develop bradycardia or hypotension28. Stocche et al. observed that, 30 minutes after receiving 150 jg of oral clonidine, 60% of the patients were "calm or sleeping"16. Those results are similar to the present study, except for the dose of clonidine, 100 jg. Intraocular surgeries with regional blocks require patients to be calm and cooperative19,21 242529. Ninety minutes after the administration of 100 and 200 jg of clonidine, 60% and 80% of the patients were sedate presenting Ramsay scores of 3 and 4 respectively while only 25% of the patients in the placebo group presented the same levels of sedation. Patients did not require supplementation of sedation, and agitation or excessive sedation was not observed. To conclude, 100 jg of clonidine can be indicated as premedication in fasciectomies due to the sedative effect, reduction in intraocular pressure, and absence of adverse effects on blood pressure and heart rate.

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RESUMEN

Cruz JRS, Cruz DFBM, Branco BC, Santiago AEQ, Amaral JLG - La Clonidina Como Medicación Preanestésica en Facectomías: Comparación entre las Dosis de 100 |jg y 200 |jg.

JUSTIFICATIVA Y OBJETIVOS: Evaluar la sedación, la presión intraocular y las alteraciones hemodinámicas con el uso de bajas dosis de clonidina, 100 jjg y 200 jjg por via oral, como medicación preanestésica para operaciones de catarata en el ambulatorio.

MÉTODO: El trabajo fue realizado por la Universidad Federal de Sao Paulo, siendo un estudio clínico aleatorio y doble ciego en 60 pacientes de los dos sexos, estado físico ASA 1 y 2, con edad minima de 18 años y máxima de 80 años. Los pacientes fueron divi-

didos en tres grupos: placebo, clonidina 1G jg y 2GG jg. Las medidas de presión intraocular, frecuencia cardiaca y presión arterial, además de la evaluación de sedación, fueron hechas antes y después de los 9 minutos iniciales en que se administró la clonidina. Los niveles de sedación se clasificaron de acuerdo con la escala de sedación de Ramsay.

RESULTADOS: Los pacientes que recibieron placebo y 1G jg de clonidina, no presentaron una reducción de la frecuencia cardiaca con diferencia estadistica significativa, mientras que los que recibieron 2GG jg de clonidina, si la presentaron. Los que recibieron clonidina en dosis de 2GG jg presentaron una reducción en la presión arterial sistólica y diastólica (p < G,G5). Un paciente que utilizó 2GG jg de clonidina, debutó con hipotensión arterial grave y presión sistólica < 8G mm Hg. Los pacientes tratados con clonidina, presentaron una reducción de la presión intraocular (p < GG5). En cuanto a la sedación, 9 minutos después de la administración del placebo y la clonidina Ш jg y 2GG jg por via oral, 25%, y de los pacientes estaba respectivamente en Ramsay 3 ó 4.

CONCLUSIONES: La dosis de WG jg de clonidina puede ser indicada como una medicación preanestésica para facectomia, con efecto en la sedación, reducción de la presión intraocular y ausencia de efectos adversos en la presión arterial sistémica y en la frecuencia cardiaca.