Safety and effectiveness of adding fentanyl or sufentanil to spinal anesthesia: systematic review and meta-analysis of randomized controlled trials

Abstract Introduction Spinal infusions of either fentanyl or sufentanil have been reported in international reports, articles, and scientific events worldwide. This study aimed to determine whether intrathecal fentanyl or sufentanil offers safety in mortality and perioperative adverse events. Methods MEDLINE (via PubMed), EMBASE, CENTRAL (Cochrane library databases), gray literature, hand-searching, and clinicaltrials.gov were systematically searched. Randomized controlled trials with no language, data, or status restrictions were included, comparing the effectiveness and safety of adding spinal lipophilic opioid to local anesthetics (LAs). Data were pooled using the random-effects models or fixed-effect models based on heterogeneity. Results The initial search retrieved 4469 records; 3241 records were eligible, and 3152 articles were excluded after reading titles and abstracts, with a high agreement rate (98.6%). After reading the full texts, 76 articles remained. Spinal fentanyl and sufentanil significantly reduced postoperative pain and opioid consumption, increased analgesia and pruritus. Fentanyl, but not sufentanil, significantly reduced both postoperative nausea and vomiting, and postoperative shivering; compared to LAs alone. The analyzed studies did not report any case of in-hospital mortality related to spinal lipophilic opioids. The rate of respiratory depression was 0.7% and 0.8% when spinal fentanyl or sufentanil was added and when it was not, respectively. Episodes of respiratory depression were rare, uneventful, occurred intraoperatively, and were easily manageable. Conclusion There is moderate to high quality certainty that there is evidence regarding the safety and effectiveness of adding lipophilic opioids to LAs in spinal anesthesia.

Incidencia de alteraciones de la frecuencia cardíaca fetal tras la inducción de analgesia del parto neuroaxial / Incidence of fetal heart rate abnormalities after neuroaxial labor analgesia induction

OBJECTIVE: To assess changes in fetal heart rate variability (FHR) after induction of neuraxial labor analgesia. MATERIALS AND METHODS: Prospective analytical cohort clinical trial conducted between July 2020 and July 2021, with fifty-nine pregnant women from the Pereira Rossell Hospital Center (CHPR) who met the inclusion criteria. Analgesic technique (epidural/spinal epidural) was randomly assigned. FHR, maternal blood pressure (BP), intensity of uterine contraction in Montevideo Units (UM) and pain using a verbal numerical scale (VAS) were monitored for 20 minutes. RESULTS: No statistically significant differences were observed for FHR at each of the times, and there were no cases of fetal bradycardia. In PA and UM, no statistically significant differences were observed. No statistically significant differences were observed for VAS at each of the times, except immediately after receiving analgesia, p value = 0.046. CONCLUSIONS: CSE was not associated with a higher risk of FHR alterations. Intrathecal fentanyl at a maximum dose of 15 mcg is safe and effective in relieving labor pain. Pain relief was similar for the two groups. No episodes of hypotension were observed. Both techniques are effective for pain relief with a similar safety profile when low doses of intraspinal fentanyl are used.

OBJETIVO: Valorar las alteraciones de la variabilidad de la frecuencia cardíaca fetal (FCF) luego de la inducción de analgesia del parto neuroaxial. MATERIALES Y MÉTODOS: Ensayo clínico prospectivo analítico de cohortes realizado entre julio de 2020 y julio de 2021, con 59 embarazadas del Centro Hospitalario Pereira Rosell (CHPR) que cumplieron con los criterios de inclusión. Se asignó de forma aleatoria la técnica analgésica (epidural/espinal-epidural). Se monitorizó durante 20 minutos la FCF, presión arterial materna (PA), intensidad de la contracción uterina en Unidades Montevideo (UM) y dolor mediante escala numérica verbal (EVA). RESULTADOS: Para la FCF en cada uno de los tiempos no se observaron diferencias estadísticamente significativas, ni hubo casos de bradicardia fetal. En la PA y UM no se observaron diferencias estadísticamente significativas. Para la EVA en cada uno de los tiempos no se observaron diferencias estadísticamente significativas, excepto inmediatamente a recibir la analgesia, valor p = 0,046. CONCLUSIONES: La CSE no se asoció a mayor riesgo de alteraciones de la FCF. El fentanil intratecal a dosis máxima de 15 mcg es seguro y efectivo para calmar el dolor del trabajo de parto. El alivio del dolor fue similar para los 2 grupos. No se observaron episodios de hipotensión. Ambas técnicas son eficaces para el alivio del dolor con similar perfil de seguridad cuando se usan dosis bajas de fentanil intrarraquídeo.

Eventos adversos associados às doses de fentanil utilizadas nos primeiros dez de vida em neonatos submetidos à correção de gastrosquise / Adverse events associated with doses of fentanyl used in the first ten days of life in neonates undergoing gastroschisis repair

Objetivo: Avaliar a associação entre as doses de fentanil utilizadas nos primeiros dez dias de vida de neonatos submetidos à correção cirúrgica de gastrosquise e as complicações respiratórias e gastrointestinais comumente associadas à essa faixa etária e defeito congênito. Métodos: O presente estudo avaliou de forma retrospectiva a coorte de recém-nascidos portadores de gastrosquise operados no IFF no período de janeiro de 2016 até junho de 2021. Dados demográficos dos neonatos e gestantes, das intervenções cirúrgicas, dos procedimentos anestésicos e dos cuidados perioperatórios em unidade de terapia intensiva neonatal foram coletados de prontuários. Os principais desfechos avaliados foram o tempo de intubação orotraqueal e de ventilação mecânica (IOT/VM), tempo de uso de NPT e data de início de dieta enteral. Foram descritos, tempo para dieta oral plena, tempo de internação em unidade de cuidados intensivos neonatais, diagnóstico de sepse, diagnóstico de apnéia, estridor, pneumonia e taxa de mortalidade. Nos primeiros dez dias de vida dos bebês, as doses de fentanil utilizadas no intraoperatório e periopratório, em bolus ou infusão contínua, foram quantificadas. Assim como, fez-se uma análise descritiva das abordagens cirúrgicas, das técnicas anestésicas e das complicações clínico-cirúrgicas apresentadas durante o período de internação na UTI. Por meio de modelagem estatística, o impacto do aumento das dose de fentanil sobre as complicações respiratórias e gastrointestinais foi avaliado. Resultados: No período do estudo 184 crianças receberam correção cirúrgica do defeito de parede no IFF e a taxa de mortalidade foi de 8,69%. Os dados de 176 neonatos foram coletados e 94% desses pacientes foram indentificadas como gastrosquise simples. Nossa coorte de 144 pacientes foi avaliada e os eventos mais frequentemente relacionados ao uso de maiores doses de fentanil foram aumento do tempo de ventilação mecânica, aumento do tempo total de uso de NPT e retardo para início da dieta enteral. Conclusão: O estudo mostrou piores desfechos respiratórios e gastrointestinais nos pacientes que receberam doses maiores de fentanil.

Objective: To evaluate the association between doses of fentanyl used in the first ten days of life in neonates undergoing surgical correction of gastroschisis and the respiratory and gastrointestinal complications commonly associated with this age group and congenital defect. Methods: This study evaluated retrospectively the cohort of newborns with gastroschisis operated at IFF between January 2016 and June 2021. Demographic data of newborns and pregnant women, surgical interventions, anesthetic procedures and perioperative care in the neonatal intensive care unit were collected from medical records. The main outcomes evaluated were time of orotracheal intubation and time on mechanical ventilation (TI/MV), time of use of PN, time to start enteral nutrition, time to full oral diet, length of stay in the neonatal intensive care unit, sepsis diagnosis, diagnosis of apnea,stridor, pneumonia and mortality rate. In the first ten days of the babies' lives, the doses of fentanyl used in the intraoperative and perioperative, in bolus or continuous infusion, were quantified. As well, a descriptive analysis of surgical approaches, anesthetic techniques and the clinical-surgical complications presented during the ICU stay was made. Through statistical modeling, the impact of increasing fentanyl doses on respiratory and gastrointestinal complications was evaluated. Results: During the study period, 184 children received surgical correction of the wall defect at IFF and the mortality rate was 8.69%. The data from 176 neonates were collected and 94% of these patients were identified as simple gastroschisis. Our cohort of 144 patients was evaluated and the most frequently related events to the use of fentanyl in higher doses were increased time on mechanical ventilation, increased total time of PN use, and delay in starting enteral feeding. Conclusion: The study demontrated worse respiratory and gastrointestinal outcomes in the neonates that received higher doses of fentanyl.

Efecto del fentanilo intratecal en hiperlagesia secundaria posoperatoria de cirugía ligamento cruzado anterior de rodilla / Effect of Intrathecal fentanyl on secondary hyperalgesia, in patients undergoing anterior cruciate ligament repair

BACKGROUND AND OBJECTIVES: Fentanyl addition is a common practice when administering spinal anesthesia. Intrathecal fentanyl has been associated to increased postoperative pain and increase morphine consumption, but considered to be related to acute opioid tolerance. This prospective, randomized, blind study evaluates the effect of intrathecal fentanyl in the development of secondary hyperalgesia, measured with Von Frey filaments, in patients undergoing anterior cruciate ligament repair. METHODS: 46 patients having anterior cruciate ligament repair, received intrathecal hyperbaric bupivacaine 13.5 mg with fentanyl 20 mcg or no fentanyl addition. Light touch pain threshold was measured with von Frey filaments before anesthesia, at 6 and 24 hours post anesthesia in the non-operated thigh and in the forearm. Visual analogue pain scores and morphine consumption were also measured at the same time. RESULTS: Baseline thresholds to mechanical stimuli were similar in both groups. In the forearm, analysis showed a decreased threshold for the non-fentanyl group at 24 h p = 0.036. In the lower extremity, control and treatment group showed lower thresholds (secondary hyperalgesia) p = 0.002 but no difference between them p = 0.795. VAS score and morphine consumption did not differ among groups. CONCLUSIONS: Spinal fentanyl added to hyperbaric bupivacaine showed no evidence of an augmented state of hyperalgesia after ACL repair, neither by pain threshold modification nor clinical outcomes. On the contrary, at 24 h, fentanyl may have a protective effect at levels above the spinal block.

ANTECEDENTES Y OBJETIVOS: El uso de fentanilo es una práctica común en la administración de anestesia espinal. Su aplicación se ha asociado a un aumento del dolor post operatorio y a un aumento en el uso de morfina; por otro lado, se ha vinculado a una tolerancia aguda a opioides. El siguiente estudio prospectivo, randomizado y ciego, evalúa los efectos del fentanilo intratecal en la aparición de hiperalgesia secundaria, medida a través de filamentos Von Frey, en pacientes operados de ligamento cruzado anterior. METODOLOGÍA: Se incluyeron a 46 pacientes operados de ligamento cruzado anterior (LCA) con una dosis intratecal de bupivacaína hiperbárica de 13,5 mg; con y sin la adición de fentanilo de 20 mcg. Se midió el umbral del dolor mecánico, a través de filamentos Von Frey, antes de la anestesia, a las 6 y 24 horas postanestesia en el muslo no operado y en el antebrazo. Al mismo tiempo, se midió la puntuación del dolor en la escala verbal numérica (EVN) y el consumo de morfina. RESULTADOS: Los umbrales basales ante la estimulación mecánica resultaron similares en ambos grupos. En el antebrazo, el análisis mostró una disminución del umbral en el grupo de pacientes sin fentanilo, a las 24 h, p = 0,036 comparado con uso de fentanilo. En el muslo, el grupo control y tratamiento mostró umbrales más bajos (hiperalgesia secundaria) p = 0,002; no obstante, no se mostraron diferencias entre ellos. No se mostraron diferencias entre las puntuaciones de la EVN y el consumo de morfina en los dos grupos. CONCLUSIÓN: No hay evidencia que la adición de fentanilo espinal, a la dosis de bupivacaína hiperbárica, haya contribuido a un aumento en la hiperalgesia tras la reparación del LCA, medido por la modificación del umbral del dolor, ni en los resultados clínicos. Al contrario a las 24 h fentanilo puede tener un efecto protector de la hiperalgesia secundaria sobre el nivel del bloqueo espinal.

Prevalence of delirium in intensive care patients and association with sedoanalgesia, severity and mortality / Prevalencia de delirio en pacientes de cuidados intensivos y asociación con la sedoanalgesia, gravedad y mortalidad / Prevalência de delirium em pacientes de terapia intensiva e associação com sedoanalgesia, gravidade e mortalidade

ABSTRACT Objective: To establish the prevalence of delirium and its subsyndrome in intensive care and to associate it with the use of sedative and analgesia, severity and mortality. Method: Carried out in two intensive care units of adult patients, this is a quantitative and transversal study, with 157 patients, using the Richmond Agitation-Sedation Scale to assess the level of sedation and the Intensive Care Delirium Screening Checklist for delirium. The T test and Chi-square test were applied for statistical analysis. Results: The prevalence of delirium was 22.3%, and 49.7% of the subsyndrome. Associations of the use of midazolam with the presence of delirium (p=0.05) and subsyndromal delirium (p<0.01), use of clonidine with the appearance of delirium (p<0.01) and of fentanyl with subsyndromal delirium (p=0.09). There were no significant differences between the mortality of patients with delirium (p=0.40) and subsyndromal delirium (p=0.86), as well as association with the mortality score. Conclusion: The use of sedoanalgesia is associated with the presence of delirium and subsyndromal delirium. No significant statistical associations were found between the severity and mortality scores.

RESUMEN Objetivo: Establecer la prevalencia del delirio y su subsíndrome en pacientes de cuidados intensivos y asociarlos con el uso de la sedoanalgesia, con la gravedad y con la mortalidad. Método: Realizado en dos unidades de cuidados intensivos de pacientes adultos, se trata de un estudio cuantitativo y transversal, con 157 pacientes, utilizando las escalas Richmond Agitation-Sedation Scale (Escala de agitación-sedación de Richmond) para evaluar el nivel de sedación y la de la Intensive Care Delirium Screening Checklist (Lista de verificación para la detección del delirio en cuidados intensivos) para el delirio. Se aplicaron las pruebas de T y Chi-cuadrado para el análisis estadístico. Resultados: La prevalencia del delirio fue del 22,3%, y la del subsíndrome fue del 49,7%. Se han encontrado asociaciones del uso de midazolan con la presencia de delirio (p = 0,05) y del deilirio subsindromático (p < 0,01), del uso de clonidina con la aparición de delirio (p < 0,01) y de fentanil con el delirio subsindromático (p = 0,09). No se registraron diferencias significativas entre la mortalidad de los pacientes con delirio (p = 0,40) y el delirio. Conclusión: El uso de sedoanalgesia se asocia con la presencia de delirio y delirio subsindromático. No se encontraron asociaciones estadísticas significativas entre la gravedad y las puntuaciones de mortalidad.

RESUMO Objetivo: Estabelecer a prevalência do delirium e sua subsíndrome em pacientes de terapia intensiva e associar com uso de sedoanalgesia, gravidade e mortalidade. Método: Realizado em duas Unidades de Terapia Intensiva de pacientes adultos, trata-se de estudo quantitativo e transversal, com 157 pacientes, utilizando as escalas Richmond Agitation-Sedation Scale para avaliação do nível de sedação e Intensive Care Delirium Screening Checklist para delirium. Foi aplicado o teste t e qui-quadrado para análise estatística. Resultados: A prevalência de delirium foi 22,3% e da subsíndrome 49,7%. Foram encontradas associações do uso de midazolan com a presença de delirium (p=0,05) e delirium subsindromático (p<0,01), uso de clonidina com o aparecimento de delirium (p<0,01) e de fentanil com o delirium subsindromático (p=0,09). Não houve diferenças significativas entre mortalidade de paciente com delirium (p=0,40) e delirium subsindromático (p= 0,86), bem como associação com o escore de mortalidade. Conclusão: O uso de sedoanalgesia está associado à presenta de delirium e delirium subsindromático. Não foram encontradas associações estatísticas significativas entre os escores de gravidade e mortalidade.

Prevalence of delirium in intensive care patients and association with sedoanalgesia, severity and mortality / Prevalencia de delirio en pacientes de cuidados intensivos y asociación con la sedoanalgesia, gravedad y mortalidad / Prevalência de delirium em pacientes de terapia intensiva e associação com sedoanalgesia, gravidade e mortalidade

ABSTRACT Objective: To establish the prevalence of delirium and its subsyndrome in intensive care and to associate it with the use of sedative and analgesia, severity and mortality. Method: Carried out in two intensive care units of adult patients, this is a quantitative and transversal study, with 157 patients, using the Richmond Agitation-Sedation Scale to assess the level of sedation and the Intensive Care Delirium Screening Checklist for delirium. The T test and Chi-square test were applied for statistical analysis. Results: The prevalence of delirium was 22.3%, and 49.7% of the subsyndrome. Associations of the use of midazolam with the presence of delirium (p=0.05) and subsyndromal delirium (p<0.01), use of clonidine with the appearance of delirium (p<0.01) and of fentanyl with subsyndromal delirium (p=0.09). There were no significant differences between the mortality of patients with delirium (p=0.40) and subsyndromal delirium (p=0.86), as well as association with the mortality score. Conclusion: The use of sedoanalgesia is associated with the presence of delirium and subsyndromal delirium. No significant statistical associations were found between the severity and mortality scores.

RESUMEN Objetivo: Establecer la prevalencia del delirio y su subsíndrome en pacientes de cuidados intensivos y asociarlos con el uso de la sedoanalgesia, con la gravedad y con la mortalidad. Método: Realizado en dos unidades de cuidados intensivos de pacientes adultos, se trata de un estudio cuantitativo y transversal, con 157 pacientes, utilizando las escalas Richmond Agitation-Sedation Scale (Escala de agitación-sedación de Richmond) para evaluar el nivel de sedación y la de la Intensive Care Delirium Screening Checklist (Lista de verificación para la detección del delirio en cuidados intensivos) para el delirio. Se aplicaron las pruebas de T y Chi-cuadrado para el análisis estadístico. Resultados: La prevalencia del delirio fue del 22,3%, y la del subsíndrome fue del 49,7%. Se han encontrado asociaciones del uso de midazolan con la presencia de delirio (p = 0,05) y del deilirio subsindromático (p < 0,01), del uso de clonidina con la aparición de delirio (p < 0,01) y de fentanil con el delirio subsindromático (p = 0,09). No se registraron diferencias significativas entre la mortalidad de los pacientes con delirio (p = 0,40) y el delirio. Conclusión: El uso de sedoanalgesia se asocia con la presencia de delirio y delirio subsindromático. No se encontraron asociaciones estadísticas significativas entre la gravedad y las puntuaciones de mortalidad.

RESUMO Objetivo: Estabelecer a prevalência do delirium e sua subsíndrome em pacientes de terapia intensiva e associar com uso de sedoanalgesia, gravidade e mortalidade. Método: Realizado em duas Unidades de Terapia Intensiva de pacientes adultos, trata-se de estudo quantitativo e transversal, com 157 pacientes, utilizando as escalas Richmond Agitation-Sedation Scale para avaliação do nível de sedação e Intensive Care Delirium Screening Checklist para delirium. Foi aplicado o teste t e qui-quadrado para análise estatística. Resultados: A prevalência de delirium foi 22,3% e da subsíndrome 49,7%. Foram encontradas associações do uso de midazolan com a presença de delirium (p=0,05) e delirium subsindromático (p<0,01), uso de clonidina com o aparecimento de delirium (p<0,01) e de fentanil com o delirium subsindromático (p=0,09). Não houve diferenças significativas entre mortalidade de paciente com delirium (p=0,40) e delirium subsindromático (p= 0,86), bem como associação com o escore de mortalidade. Conclusão: O uso de sedoanalgesia está associado à presenta de delirium e delirium subsindromático. Não foram encontradas associações estatísticas significativas entre os escores de gravidade e mortalidade.

Caracterización de las potenciales interacciones farmacológicas en pacientes de una unidad de cuidados intensivos en un hospital de tercer nivel de Bogotá / Characterization of potential drug-drug interactions in patients hospitalized in the intensive care unit of a tertiary hospital in Bogotá

Resumen Introducción. Las interacciones farmacológicas ocurren con mayor frecuencia en las unidades de cuidados intensivos que en otros servicios. Sin embargo, en Colombia son pocos los estudios en que se han evaluado en pacientes críticamente enfermos. Objetivos. Caracterizar las potenciales interacciones farmacológicas en las prescripciones de pacientes hospitalizados en una unidad de cuidados intensivos y determinar los factores asociados con su aparición. Materiales y métodos. Se analizó una cohorte retrospectiva de pacientes hospitalizados en una unidad de cuidados intensivos, durante un periodo de siete meses. Las prescripciones diarias se evaluaron en busca de potenciales interacciones farmacológicas mediante el programa Lexicomp™. Se calculó la incidencia de interacciones, se clasificaron según su tipo, gravedad y grado de documentación, y se evaluaron los factores asociados con su aparición mediante regresión logística. Resultados. La proporción de pacientes con por lo menos una interacción fue de 84 %, en tanto que el 87 % presentó más de una interacción; la mediana fue de seis interacciones por paciente. La más frecuente fue entre el fentanilo y el midazolam (23 %). Las interacciones de gravedad y grado de documentación moderados fueron las más frecuentes (77,6 y 52,6 %, respectivamente). El fármaco índice más frecuente fue el midazolam (12 %) y el precipitante más frecuente, el fentanilo (10,6 %). La edad (odds ratio, OR=3,1) y el número de medicamentos (OR=11,8), se asociaron con la aparición de interacciones. Conclusiones. Dada su elevada frecuencia y potencial impacto negativo es importante vigilar sistemáticamente las prescripciones en cuidados intensivos para detectar las interacciones, con el fin de contribuir al uso racional de los medicamentos y a mejorar la calidad de la atención.

Abstract Introduction: Drug-drug interactions occur more frequently in intensive care units than in other services. However, in Colombia, there are few studies on this problem in critically ill patients. Objectives: To characterize potential drug-drug interactions generated from prescriptions during hospitalization in an intensive care unit and to determine factors associated with their onset. Materials and methods: A retrospective cohort was assembled with patients hospitalized in an intensive care unit for a seven-month period. The daily prescription was assessed for potential drugdrug interactions using the Lexicomp® program. We calculated the incidence of interactions, classified them by type, severity, and level of documentation, and evaluated the factors associated with their onset using logistic regression. Results: The proportion of patients with at least one interaction was 84% while 87% had more than one interaction; the median was six interactions per patient. The most frequent was fentanyl and midazolam (23%). Moderate interactions were the most frequent by severity (77.6%) and by documentation (52.6%). The most common index and precipitating drugs were midazolam (12%) and fentanyl (10.6%), respectively. Age (OR=3.1) and the number of drugs (OR=11.8) were associated with the occurrence of interactions. Conclusions: Given their high frequency and potential negative impact, the systematic monitoring of prescriptions in intensive care units to detect interactions is important. Such monitoring contributes to the rational use of medicines and to improve the quality of care.

Safety degree assessment of drugs used in conscious sedation for colonoscopy in patients that develop respiratory depression / Avaliação do grau de segurança dos fármacos utilizados na sedação superficial na colonoscopia em pacientes que desencadeiam depressão respiratória

ABSTRACT Objective: To analyze the safety degree of drugs used in colonoscopy during conscious sedation in patients developing respiratory depression. Methods: Cross-sectional observational study that evaluated 1120 patients who underwent colonoscopy between February 2015 and February 2016. Physical characteristics, surgical history and previous colonoscopies, indication and conditions of the current examination, fentanyl and midazolam doses and subsequent complications were analyzed. Level of significance: p < 0.05. Chi-square test was used for association of categorical variables, whereas Student's t test was used to compare means and Spearman's coefficient for correlation. Results: There were 661 female (59%) and 459 (41%) male patients, with a mean age of 54.90 (20-87) years and BMI of 27.00 (14.5-45.4). Of the 1120 patients, only 2 (0.2%) had respiratory depression, reversed with lanexat. Patients who had complications were of both genders, with a body mass index of 21.25 and 28.7. There was a correlation between the required dose of fentanyl and age (p < 0.001 to −0.121 Spearman's coefficient), as well as midazolam (p < 0.001 - Spearman's coefficient −0.452) and increasing age was associated with a lower dose of the drug. Conclusion: The number of patients with complications was 0.17%. The age of the patient showed an inverse association, i.e., the older the patient, the lower the required dose of medication. The drugs used in colonoscopy show a high degree of safety, corroborating their frequent use for superficial/conscious sedation in this procedure.

RESUMO Objetivo: Analisar o grau de segurança dos fármacos utilizados na colonoscopia sob sedação superficial em pacientes que desencadeiam depressão respiratória. Métodos: Estudo observacional transversal, que avaliou 1.120 pacientes que realizaram colonoscopia entre Fevereiro de 2015 e Fevereiro de 2016. Analisaram-se características físicas, histórico cirúrgico e colonoscopias prévias, indicação e condições do exame atual, dose de fentanil e midazolam e complicações apresentadas. Nível de significância adotado: p < 0,05. Utilizou-se teste Qui-quadrado para associação de variáveis categóricas, teste t de Student para comparação de médias e coeficiente de Spearman para correlação. Resultados: Foram 661 pacientes do sexo feminino (59%) e 459 (41%) do sexo masculino, com média de idade de 54,90 (20-87) anos e IMC de 27,00 (14,5-45,4). Dos 1120 pacientes, apenas 2 (0,2%) exibiram depressão respiratória revertida com lanexate. Os pacientes que apresentaram complicação eram de sexos diferentes, com índices de massa corpórea de 21,25 e 28,7. Houve correlação entre a dose necessária de fentanil e a idade (p < 0,001 - coef Spearmann - 0.121), assim como a de midazolam (p < 0,001 - coef Spearmann - 0.452), sendo que com o aumento da idade se correlacionou com uma menor dose utilizada de medicamento. Conclusão: O número de pacientes que apresentaram alguma complicação foi 0,17%. A idade do paciente tem associação inversa, quanto maior a idade do paciente, menor é a dose necessária de medicamentos. Verifica-se alto grau de segurança dos medicamentos utilizados na colonoscopia, corroborando sua utilização frequente para a sedação superficial/consciente neste procedimento.

The effect of pheniramine on fentanyl-induced cough: a randomized, double blinded, placebo controlled clinical study / Efeito de feniramina sobre a tosse induzida por fentanil: estudo clínico, randômico, duplo-cego e controlado com placebo

Abstract Background and objectives: There are many studies conducted on reducing the frequency and severity of fentayl-induced cough during anesthesia induction. We propose that pheniramine maleate, an antihistaminic, may suppress this cough. We aim to observe the effect of pheniramine on fentanyl-induced cough during anesthesia induction. Methods: This is a double-blinded, prospective, three-arm parallel, randomized clinical trial of 120 patients with ASA (American Society of Anesthesiologists) physical status III and IV who aged ≥18 and scheduled for elective open heart surgery during general anesthesia. Patients were randomly assigned to three groups of 40 patients, using computer-generated random numbers: placebo group, pheniramine group, and lidocaine group. Results: Cough incidence differed significantly between groups. In the placebo group, 37.5% of patients had cough, whereas the frequency was significantly decreased in pheniramine group (5%) and lidocaine group (15%) (Fischer exact test, p = 0.0007 and p = 0.0188, respectively). There was no significant change in cough incidence between pheniramine group (5%) and lidocaine group (15%) (Fischer exact test, p = 0.4325). Cough severity did also change between groups. Post Hoc tests with Bonferroni showed that mean cough severity in placebo differed significantly than that of pheniramine group and lidocaine group (p < 0.0001 and p = 0.009, respectively). There was no significant change in cough severity between pheniramine group and lidocaine group (p = 0.856). Conclusion: Intravenous pheniramine is as effective as lidocaine in preventing fentayl-induced cough. Our results emphasize that pheniramine is a convenient drug to decrease this cough.

Resumo Justificativa e objetivos: Há muitos estudos sobre a redução da frequência e da gravidade da tosse induzida por fentanil durante a indução da anestesia. Propomos que maleato de feniramina, um anti-histamínico, pode suprimir essa tosse. Nosso objetivo foi observar o efeito de feniramina sobre a tosse induzida por fentanil durante a indução da anestesia. Métodos: Este é um estudo clínico prospectivo, de três braços paralelos, randômico e duplo-cego, de 120 pacientes com estado físico ASA III e IV (de acordo com a Sociedade Americana de Anestesiologistas), ≥ 18 anos e programados para cirurgia cardíaca aberta eletiva sob anestesia geral. Os pacientes foram divididos aleatoriamente em três grupos de 40 pacientes cada, com números aleatórios gerados por computador: grupo placebo, grupo feniramina e grupo lidocaína. Resultados: A incidência de tosse diferiu significativamente entre os grupos. No grupo placebo, 37,5% dos pacientes apresentaram tosse, enquanto que a frequência foi significativamente reduzida no grupo feniramina (5%) e no grupo lidocaína (15%) (teste exato de Fischer, p = 0,0007 e p = 0,0188, respectivamente). Não houve alteração significativa na incidência de tosse entre os grupos feniramina (5%) e lidocaína (15%) (teste exato de Fischer, p = 0,4325). A gravidade da tosse também alterou entre os grupos. Testes post hoc com Bonferroni mostraram que a média da gravidade da tosse no grupo placebo diferiu significativamente das médias dos grupos feniramina e lidocaína (p < 0,0001 e p = 0,009, respectivamente). Não houve alteração significativa na gravidade da tosse entre o grupo feniramina e grupo lidocaína (p = 0,856). Conclusão: Feniramina por via intravenosa tem a mesma eficácia que lidocaína na prevenção da tosse induzida por fentanil. Os resultados enfatizam que feniramina é um medicamento conveniente para diminuir essa tosse.

Association of lipophilic opioids and hyperbaric bupivacaine in spinal anesthesia for elective cesarean section. Randomized controlled study

PURPOSE: To evaluate the efficacy and side-effects of fentanyl and sufentanil combined with hyperbaric spinal bupivacaine in elective cesarean section. METHODS: A prospective, randomized, double-blind study with 64 term parturients, distributed into 2 groups according to the opioid combined with hyperbaric bupivacaine 0.5% (10mg): GF - fentanyl (25µg) and GS - sufentanil (5.0µg). The latency and maximum sensory block level; degree and duration of motor block; duration and quality of analgesia; maternal-fetal repercussions were evaluated. This was an intention-to-treat analysis with a 5% significance level. RESULTS: The latency period, maximum sensory block level, motor block degree and perioperative analgesia were similar in both groups. Motor block and analgesia had a longer duration in the sufentanil group. Maternal adverse effects and neonatal repercussions were similar. The incidence of hypotension was higher in the fentanyl group. In both groups, there was a predominance of patients who were awake and either calm or sleepy. CONCLUSIONS: The addition of fentanyl and sufentanil to hyperbaric subarachnoid bupivacaine was shown to be effective for the performance of cesarean section, and safe for the mother and fetus. Analgesia was more prolonged with sufentanil. .

Impacto do fentanil associado ao midazolam na sedação para ecocardiograma transesofágico / Impact of fentanyl associated with midazolam in sedation for transesophageal echocardiography / Impacto del Fentanil Asociado al Midazolam en la Sedación para Ecocardiograma Transesofágico

Introdução: O ecocardiograma transesofágico é atualmente uma das principais ferramentas no diagnóstico de diversas alterações cardíacas. Para uma maior segurança e conforto na sua realização, o exame tem sido realizado sob sedação consciente moderada, sendo os benzodiazepínicos os agentes de escolha. Nessa classe de medicamentos, o midazolam é o mais utilizado, todavia não está isento de possíveis complicações relacionadas ao seu uso, como hipóxia, hipotensão, entre outras. Sabemos que grau de sedação é dose-dependente, portanto, quanto menor a dose utilizada, será menor o risco de complicações do procedimento.Objetivo: Verificar o impacto do uso do fentanil na administração endovenosa de midazolam, no intuito de avaliar eficiência de protocolo de sedação de pacientes submetidos a ecocardiograma transesofágico, utilizando ambos os medicamentos. Metodologia: : Estudamos 201 pacientes (idade média de 51,5 anos, 115 homens) submetidos a ecocardiograma transesofágico, com sedação por via endovenosa divididos em dois grupos: Grupo A (n = 89), seguindo protocolo definido com uso de fentanil associado ao midazolam; e Grupo B (n = 112), sem o emprego de fentanil. Comparou-se então a dosagem de midazolam administrada em ambos os grupos. Monitorização adequada dos sinais vitais foi realizada durante todo o procedimento. Resultados: A dose média de midazolam utilizada foide 2,6 ± 1,4 mg no Grupo A e de 4,0 ± 2,7 mg no Grupo B (p < 0,01). A dose de fentanil empregada foi de 66,2 ± 24,8 mcg. Não houve diferença significativa entre idade (p = 0,08) e gênero (p > 0,1) nos grupos estudados. Conclusão: O uso de fentanil na sedação para realização de ecocardiograma transesofágico associado à administração de midazolam permite a administração de uma dose menor desse benzodiazepínico.

Introduction: Transesophageal echocardiography is currently one of the main tools in the diagnosis of various cardiac abnormalities. For greater safety and comfort, the test has been performed under moderate conscious sedation and benzodiazepines were the agents of choice. In this class of drugs, midazolam is the most commonly used, however it is not free of potential complications related to its use, such as hypoxia, hypotension, among others. We know that sedation level is dose-dependent. Therefore, the lower the dose, the lower the risk of complications from the procedure.Objective: To check the impact of fentanyl in the intravenous administration of midazolam in order to assess the sedation protocol efficiency on patients undergoing transesophageal echocardiography using both drugs.Methodology: We have studied 201 patients (mean age 51.5 years, 115 men) who underwent transesophageal echocardiography with intravenous sedation divided into two groups: Group A (n = 89), following the protocol with fentanyl associated with midazolam; and Group B (n = 112) without the use of fentanyl. The dose of midazolam administered in both groups was then compared. Proper monitoring of vital signs was performed throughout the procedure.Results: The mean dose of midazolam used was 2.6 ± 1.4 mg in Group A and 4.0 ± 2.7 mg in Group B (p < 0.01). The dose of fentanyl used was 66.2 ± 24.8 mcg. There was no significant difference between age (p = 0.08) and gender (p > 0.1) in the groups studied. Conclusion: The use of fentanyl in sedation for transesophageal echocardiography associated with administration of midazolam allows the administration of a lower dose of this benzodiazepine.

Introducción: El ecocardiograma transesofágico es actualmente una de las principales herramientas en el diagnóstico de diversas alteraciones cardíacas. Para una mayor seguridad y confort en su realización, el examen ha sido realizado bajo sedación conciente moderada, siendo los benzodiazepínicos los agentes de elección. En esa clase de medicamentos, el midazolam es el más utilizado, sin embargo no está exento de posibles complicaciones relacionadas a su uso, como hipoxia, hipotensión, entre otras. Sabemos que grado de sedación es dosis-dependiente, por lo tanto, cuanto menor es la dosis utilizada, será menor el riesgo de complicaciones del procedimiento.Objetivo: Verificar el impacto del uso del fentanil en la administración endovenosa de midazolam, con el propósito de evaluar eficiencia de protocolo de sedación de pacientes sometidos a ecocardiograma transesofágico, utilizando ambos medicamentos.Metodología: Estudiamos 201 pacientes (edad media de 51,5 anos, 115 hombres) sometidos a ecocardiograma transesofágico, con sedación por vía endovenosa divididos en dos grupos: Grupo A (n = 89), siguiendo protocolo definido con uso de fentanil asociado al midazolam; y Grupo B (n = 112), sin el empleo de fentanil. Se comparó entonces el dosaje de midazolam administrada en ambos grupos. Monitoreo adecuado de los signos vitales fue realizada durante todo el procedimiento. Resultados: La dosis media de midazolam utilizada fue de 2,6 ± 1,4 mg en el Grupo A y de 4,0 ± 2,7 mg en el Grupo B (p < 0,01). La dosis de fentanil empleada fue de 66,2 ± 24,8 mcg. No hubo diferencia significativa entre edad (p = 0,08) y género (p > 0,1) en los grupos estudiados. Conclusión: El uso de fentanil en la sedación para realización de ecocardiograma transesofágico asociado a la administración de midazolam permite la administración de una dosis menor de ese benzodiazepínico

Incidence and Risk Factors of Postoperative Nausea and Vomiting in Patients with Fentanyl-Based Intravenous Patient-Controlled Analgesia and Single Antiemetic Prophylaxis

PURPOSE: We evaluated the incidence and risk factors of postoperative nausea and vomiting (PONV) in patients with fentanyl-based intravenous patient-controlled analgesia (IV-PCA) and single antiemetic prophylaxis of 5-hydroxytryptamine type 3 (5 HT3)-receptor antagonist after the general anesthesia. MATERIALS AND METHODS: In this retrospective study, incidence and risk factors for PONV were evaluated with fentanyl IV-PCA during postoperative 48 hours after various surgeries. RESULTS: Four hundred-forty patients (23%) of 1878 had showed PONV. PCA was discontinued temporarily in 268 patients (14%), mostly due to PONV (88% of 268 patients). In multivariate analysis, female, non-smoker, history of motion sickness or PONV, long duration of anesthesia (>180 min), use of desflurane and intraoperative remifentanil infusion were independent risk factors for PONV. If one, two, three, four, five, or six of these risk factors were present, the incidences of PONV were 18%, 19%, 22%, 31%, 42%, or 50%. Laparoscopic surgery and higher dose of fentanyl were not risk factors for PONV. CONCLUSION: Despite antiemetic prophylaxis with 5 HT3-receptor antagonist, 23% of patients with fentanyl-based IV-PCA after general anesthesia showed PONV. Long duration of anesthesia and use of desflurane were identified as risk factors, in addition to risk factors of Apfel's score (female, non-smoker, history of motion sickness or PONV). Also, intraoperative remifentanil infusion was risk factor independent of postoperative opioid use. As the incidence of PONV was up to 50% according to the number of risk factors, risk-adapted, multimodal or combination therapy should be applied.

Progressive Change in Joint Degeneration in Patients with Knee or Hip Osteoarthritis Treated with Fentanyl in a Randomized Trial

PURPOSE: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. MATERIALS AND METHODS: Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. RESULTS: Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. CONCLUSION: Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.

Remifentanilo en anestesia general / Remifentanil in general anesthesia

El remifentanilo es un agonista de los receptores mu, con una relativa unión a los receptores kappa y delta. Es un derivado piperidínico similar al resto de los fentanilos, pero incluye en su molécula un enlace éster. Su potencia analgésica es 2 a 3 veces la del fentanilo. El grupo químico éster permite que sea metabolizado por esterasas sanguíneas y de otros tejidos, permitiendo un extenso y rápido metabolismo, sin participación hepática. Su comienzo de acción es rápido y tiene una vida media de 3.8 a 6.3 minutos. Se une aproximadamente un 70% a las proteínas plasmáticas. No se acumula en tejidos periféricos como el músculo o la grasa. No está influenciado por la deficiencia de la pseudocolinesterasa. Tampoco es influenciada por los \r\nfallos renales o hepáticos en tanto y en cuanto en tanto no alteren la concentración de proteínas. Se realizó \r\nuna búsqueda bibliográfica en Medline, Cochrane, Lilacs, CRD Universidad de York, TripDatabase, Google académico y otros buscadores y bases de datos de internet. Se buscaron principalmente revisiones sistemáticas, meta-análisis, evaluaciones económicas y evaluaciones de tecnologías sanitarias que compararan remifentanilo contra fentanilo para anestesia general. Se encontraron 1 meta-análisis y 3 evaluaciones económicas.Comparado con fentanilo, no se observaron diferencias significativas en cuanto a eficacia y seguridad en puntos finales relevantes. Los esquemas de anestesia general que emplean remifentanilo en lugar de fentanilo ofrecen prácticamente los mismos niveles de seguridad y eficacia, con algún potencial beneficio marginal. El costo de utilizar Remifentanilo en lugar de Fentanilo parece ser igual o probablemente menor. Se recomienda la incorporación de remifentanilo al Formulario Terapéutico Provincial \r\ncomo adyuvante analgésico en la inducción o mantenimiento de la anestesia general.

[Evaluation of pre-medication with oral clonidine on fentanyl induced cough during general anesthesia]

A reflex cough is often observed after intravenous bolus of fentanyl. This study was conducted to determine whether pre-treatment with oral clonidine could attenuate fentanyl-induced cough. Two groups, containing 80 patients each, were candidated for elective surgery under general anesthesia. They were randomly divided into case group, receiving preoperative oral clonidine tablet, and control group, receiving preoperative placebo. Then gathered data was analyzed with Chi - square, Mann-Whitney U, T-Student and Tukey tests by 13 spss software, version 13. The results were evaluated as the mean +/- SD and considered statistically significant for p <0.05. Two groups were similar with demographic parameters as age, weigh and sex [p>0.05]. In the clonidine group severity and frequency of fentanyl induced cough were lower [p<0.05]. The OAA/S scaling score in two groups were similar [p>0.05]. Pre-medication with oral clonidine can effectively attenuate fentanyl-induced cough with an unknown mechanism

Fentanyl: efectos adversos en anestesia subaracnoidea con Bupivacaína / Adverse side effects of fetanyl plus bupivacaine subarachnoid anesthesia

Los efectos adversos de los opioides son el resultado de interacciones con sus receptores a nivel cerebral. Cuando se administran por vía intratecal se ha descrito depresión respiratoria, aunque con menor frecuencia que en uso endovenoso. Objetivo: describir la ocurrencia de efectos adversos en pacientes llevados a cirugía en el Hospital de San José de Bogotá D.C. que recibieron fentanyl intratecal como adición a bupivacaína hiperbárica. Materiales y métodos: estudio descriptivo de una cohorte de pacientes llevados a cirugía en el Hospital de San José entre 1º de octubre de 2007 y 30 de septiembre de 2009, que recibieron anestesia subaracnoidea aplicando fentanyl intratecal y bupivacaína hiperbárica. Se incluyeron los pacientes de 18 a 65 años, las no gestantes y aquellos sin conversión a anestesia general. Resultados: se estudiaron 313 pacientes, 39,9% mujeres con edad promedio de 42 años (DE:12,7), clasificación ASA distribuida en ASA I, 60,7%; ASA II, 33,3%; ASA III, 5,7% y ASA IV, 0,3%. Los efectos adversos más comunes fueron náuseas 8,6% (n:27), prurito 6,7%(n:21), vómito 2,2% (n:7) y bradicardia 2,2% (n:7). La depresión respiratoria se presentó en 1,3% (n:4). Conclusiones: la frecuencia de depresión respiratoria que reportamos se encuentra en el rango de la literatura; sin embargo, hay que considerar que no existe consenso en la manera como se mide. Los demás eventos adversos fueron menos que los reportados.

Adverse effects of opioids result of their interactions with opioid brain receptors. Intrathecal administration of fentanyl may induce respiratory depression but less frequently than when intravenously administered. Objective: to describe the frequency of adverse side effects in surgical patients at Hospital de San José who received intrathecal fentanyl plus hyperbaric bupivacaine. Materials and Methods: descriptive study of a cohort of patients who underwent surgery at Hospital de San José between October 1 2007 and September 30 2009, who received intratecal fentanyl plus hyperbaric bupivacaine. Patients aged 18 to 65 years, nonpregnant women and those who were not converted into general anesthesia were included. Results: 313 patients were studied, 39.9% women with mean age 42 years (SD: 12.7), classified as: ASA I 60.7%; ASA II, 33.3%; ASA III, 5.7% and ASA IV, 0.3%. The most common adverse side effects were, nausea 8.6% (n: 27), pruritus 6.7% (n: 21), vomiting 2.2% (n: 7) and bradycardia 2.2% (n: 7). Respiratory depression presented in 1.3% (n: 4). Conclusions: our report of the frequency of respiratory depression is within that described in literature; however, it must be considered that the measuring methods were not consistent. Other adverse events were lower than those reported.

Naloxone-induced pulmonary edema: a potential cause of postoperative morbidity in laparoscopic donor nephrectomy.

A 28-year-old patient operated for laparoscopic donor nephrectomy (LDN) developed overdose effect of fentanyl leading to poor postoperative recovery. Naloxone (200 microg) treatment was used to reverse fentanyl effects, but it was associated with hypertension. The patient developed pulmonary edema after 2 hours and required overnight mechanical ventilation with positive end-expiratory pressure. Volume overload prescribed in the management of LDN to overcome the immediate poor renal graft functioning probably predisposed this healthy young patient to develop cardiac failure during sympathetic surge associated with naloxone administration. The authors feel that the reversal of overdose effect of opioid by naloxone after intravascular blood volume expansion puts the patient at risk to develop pulmonary edema.

non opioid fast track anesthetic regimen for colonic resection

Fast-tracking implies a preoperative patient care paradigm that reduces time to recovery and discharge. The current study adopted fast-track anesthetic techniques, comparing outcome of a multimodal non-opioid and another opioid regimen, on recovery profiles after colonic surgery, with standard anesthetic practice. Seventy five ASA II colectomy patients were randomly assigned to one of three groups. Control group for conventional general anesthetic technique and two fast-track anesthesia groups using combined light general anesthesia and epidural techniques. Epidural maintenance was by infusion cocktail of bupivacaine-fentanyl in opioid-based group, while in non-opioid group by bupivacaine-ketamine which were both continued postoperatively for pain in lower doses and concentrations. Postoperative analgesia in control group was achieved by morphine. Supplemental ketorolac and acetaminophen were added only to non-opioid group. Early and intermediate recovery profiles were compared among the three groups together with recorded side effects. All patients in fast-track groups had significant shorter times to: awakening, extubation, orientation, both PACU arrival and discharge, hospital stay with a significant lower mean VAS for pain at rest, and rescue analgesia, compared to control group. Control group had a significant higher rate of postoperative nausea and vomiting, drowsiness and pruritis. Non-opioid fast-track regimen had a significant shorter PACU and hospital stay with lower side-effects rate than opioid one. Fast-track anesthesia enhanced recovery profile. Non-opioid regimen was superior to opioid-based, having a better recovery profile and a lower rate of side-effects

Prophylactic intravenous ondansteron and nalbuphine for reduction of subarachnoid fentanyl-induced pruritus in patients undergoing elective cesarean delivery

Addition of fentanyl to spinal anaesthesia with bupivacaine improves the quality and success of anaesthesia. However, it has a frequent incidence of pruritus and a substantial incidence of nausea and vomiting. tn this placebo controlled study, we compared the prophylactic efficacy of ondansetron and nalbuphine for the prevention of intrathecal fentanyl-induced pruri tus after cesarean delivery. Ninety elective parturients were assigned to one of the groups: Group 0 [Ondansetron 8mg IV n=30], Group N [Nalbuphine 4mg IV n=30] and Group S [Saline 0.9% IV n=30] as placebo. The study drugs were administered immediately after the umbilical cord was clamped. The occurrence of pruritus, nausea, pain and adverse reactions from ondansetron and nalbuphine was evaluated by pruritus score, 4-point rating score and visual analog scale respectively, at 15 minutes in the first hour after the injection of the study drugs. Afterward, evaluations were performed at 1, 2, 3 and 4 hours after the administration of study drugs. The overall incidence of pruritus, it was significantly more frequent in Group S [62%] compared with both Group 0 [43%] and Group N [42.5%]. The incidence of pruritus during the different study intervals showed significant increase in Group S compared with the other groups mainly at 45mm and 1 hour. The pruritus score was significantly different between Group 0 and Group S and between Group N and Group S [p<0.0S] respectively, it was mostly mild in Group 0 and Group N and mostly moderate in Group S. Treatment for pruritus was requested by patients in, 10%, 11% and 29% of patients in the Group 0, Group N and Group 5, respectively. There was no significant difference in the overall incidence and the severity of nausea andlor vomiting at different time study intervals for all groups. However, the number of patients requesting treatment for nausea and/or vomiting was significantly less in Group 0 and Group N when compared with Group S. No significant adverse reactions related to the study drugs reported during the different study intervals. Although IV ondansetron and nalbuphine significantly decreased the incidence of of fentanyl-induced pruritus more than placebo after cesarean delivery, further studies are recommended to show the other possible mecha nisms might be involved in the pathogenesis of fentanylinduced pruritus