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.

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

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.

Spinal anesthesia for elective cesarean section. Bupivacaine associated with different doses of fentanyl: randomized clinical trial.

OBJECTIVE: Assess patients submitted to elective cesarean section under spinal anesthesia, and the efficacy of different doses of fentanyl associated with bupivacaine. METHODS: The study included 124 pregnant women randomly distributed into 4 groups (n = 31) according to different doses of fentanyl (15 µg, 10 µg, 7.5 µg), Groups I, II, and III, respectively, and control group IV, associated with 0.5% hyperbaric bupivacaine (10 mg). An epidural catheter was inserted in case epidural top-up was required. We assessed the anesthetic blockage characteristics, negative maternal and neonatal outcomes, and maternal side effects. Statistical analysis was performed using Kruskal-Wallis, Fisher's exact and chi-square tests. The level of significance was 5% (p < 0.05). RESULTS: The quality of analgesia, time for the first complaint of pain and motor block recovery time were significantly better for groups that received fentanyl in comparison to controls (p < 0.001). None of the groups had negative maternal-fetal outcomes. Nausea was significantly more frequent in patients in Groups II (10 µg) and III (7.5 µg) when compared to Groups I (15 µg) and IV (no fentanyl). Vomiting was more frequent in Group III than in Group I (p = 0.006). The incidence of pruritus was significantly higher in the groups receiving fentanyl (p = 0.012). CONCLUSIONS: Among the solutions studied, the spinal anesthesia technique using 15 µg of fentanyl associated with 10 mg of hyperbaric bupivacaine provided satisfactory analgesia and very low incidence of adverse effects for patients submitted to cesarean section. TRIAL REGISTRATION NUMBER: UTN U1111-1199-0285. REBEC: RBR-5XWT6T.

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.

Prevalence of delirium in intensive care patients and association with sedoanalgesia, severity and mortality.

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.

Evaluation of a Safety Protocol for the Management of Thirst in the Postoperative Period.

PURPOSE: To associate medications, anesthetic techniques, and clinical conditions that interfere in the time of patient approval in the safety protocol for thirst management. DESIGN: A quantitative, analytical, and longitudinal study conducted in Southern Brazil. METHODS: A nonprobabilistic sample, of 203 adult patients in the immediate postoperative period, evaluated every 15 minutes for 1 hour. FINDINGS: A general prevalence of thirst of 67.7%, and mean intensity of 6.38. Fentanyl, morphine, rocuronium, and sevoflurane increased lack of approval in the protocol within 30 minutes (P < .05). General anesthesia (P < .0001) and level of consciousness (95.4%) presented the highest nonapproval rates. CONCLUSIONS: Anesthetics and general anesthesia delayed protocol approval; however, after 30 minutes, 75.4% of patients had been approved. Level of consciousness was the main criterion of disapproval. The protocol identified crucial clinical conditions that made it impossible for the patient to receive thirst relief strategies and demonstrated that thirst can be satiated precociously with safety.

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.

Characterization of potential drug-drug interactions in patients hospitalized in the intensive care unit of a tertiary hospital in Bogotá

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.

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.

Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial.

PURPOSE: Continuous epidural infusion and programmed intermittent epidural boluses are analgesic techniques routinely used for pain relief in laboring women. We aimed to assess both techniques and compare them with respect to labor analgesia and obstetric outcomes. METHODS: After Institutional Review Board approval, 132 laboring women aged between 18 and 45 years were randomized to epidural analgesia of 10 mL of a mixture of 0.1% bupivacaine plus 2 µg/mL of fentanyl either by programmed intermittent boluses or continuous infusion (66 per group). Primary outcome was quality of analgesia. Secondary outcomes were duration of labor, total drug dose used, maternal satisfaction, sensory level, motor block level, presence of unilateral motor block, hemodynamics, side effects, mode of delivery, and newborn outcome. RESULTS: Patients in the programmed intermittent epidural boluses group received statistically less drug dose than those with continuous epidural infusion (24.9 vs 34.4 mL bupivacaine; P = 0.01). There was no difference between groups regarding pain control, characteristics of block, hemodynamics, side effects, and Apgar scores. CONCLUSIONS: Our study evidenced a lower anesthetic consumption in the programmed intermittent boluses group with similar labor analgesic control, and obstetric and newborn outcomes in both groups.

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.

The effect of pheniramine on fentanyl-induced cough: a randomized, double blinded, placebo controlled clinical study.

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.

Opioid and Benzodiazepine Withdrawal Syndrome in PICU Patients: Which Risk Factors Matter?

BACKGROUND AND AIMS: Although iatrogenic withdrawal syndrome (IWS) has been recognized in patients exposed to opioids and benzodiazepines, very few studies have used a validated tool for diagnosis and assessment of IWS in critically ill children. We sought to determine IWS rate, risk factors, and outcomes of IWS patients. METHODS: Prospective observational study conducted in a pediatric intensive care unit. A total of 137 patients (31 with IWS and 106 with no IWS) received a continuous infusion of fentanyl and midazolam for 3 or more days. The Sophia Observation withdrawal Symptoms scale was repeatedly applied when children were weaned off sedation/analgesia. RESULTS: The overall incidence of IWS was 22.6%. Of the 31 IWS patients, 6 showed IWS with less than 5 days sedation or analgesia. Logistic regression showed that the median peak dose of midazolam was associated with IWS development (odds ratio 1.4). Receiver-operating curve showed a cut-off value of 0.35 mg/kg/h for midazolam peak dose (sensitivity 96.7%, specificity 51%, positive predictive value 36.6%, and negative predictive value 98.2%), with area under the curve of 0.80. IWS patients had a longer time on mechanical ventilation, prolonged pediatric intensive care unit, and hospital stays, and required prolonged period to have drugs discontinued. CONCLUSIONS: Although length of sedation/analgesia for at least5 days has been widely proposed for monitoring IWS, our data suggest that initiating monitoring after 3 sedation days is highly recommended. In addition, patients requiring infusion rates of midazolam above 0.35 mg/kg/h should be considered at high risk for IWS.

Serotonin Syndrome Induced by Fentanyl in a Child: Case Report.

Serotonin syndrome (SS) is a potentially fatal condition associated with increased serotonergic activity in the central nervous system that can be attributed to certain drugs or interactions between drugs. There are some published articles reporting this syndrome caused by the combination of fentanyl and selective serotonin reuptake inhibitors antidepressants in adult patients; however, there are no reports of SS associated to the use of fentanyl as a single causative agent. The author reports a case of a 7-year-old boy who was admitted to the emergency department with neurological deterioration secondary to an intracerebral hemorrhage. The patient was operated to remove the bleeding. Postoperatively, he experienced a diversity of progressive neurological signs (shivering, tremor, hypertonia, hyperreflexia, clonus, bilateral mydriasis, and intracranial hypertension), which were initially considered to be signs of neurological deterioration, but finally, it was proved that they were part of a SS caused by fentanyl.The absence of concomitant use of another medications known to induce SS and the dramatic improving observed after stopping fentanyl strongly indicates that fentanyl was the causative agent in this case of SS.Fentanyl is a medication used frequently, and therefore, clinicians should be aware of this potential adverse effect when this drug is administered.

Safety of deep sedation in young children with sickle cell disease: a retrospective cohort study.

OBJECTIVE: To assess the rates and types of complications associated with deep sedation in children with sickle cell disease (SCD) and to explore potential risk factors. STUDY DESIGN: This was a retrospective cohort study of children with SCD and a comparison group of children without SCD who underwent magnetic resonance imaging with deep sedation. The rates of general and SCD-associated sedation complications were calculated, and potential associated clinical and laboratory variables were assessed. RESULTS: A total of 162 sedation records in 94 subjects with SCD and 324 sedation records in 321 subjects without SCD were assessed (mean age, 4.3 years in both groups). Pentobarbital, fentanyl, and midazolam were used in the majority of sedation episodes without routine presedation transfusion. Sedation-related complication rates did not differ significantly between the SCD and comparison groups. Within 1 month after the sedation procedure, 17 children (10%) experienced a vaso-occlusive pain episode (VOE), and 2 children (1.2%) developed acute chest syndrome. Preprocedure and postprocedure rates of these complications did not differ significantly. Subjects who developed VOE after sedation had a significantly higher VOE rate before sedation, but no other significant clinical or laboratory risk factors were identified. CONCLUSION: Deep sedation in young children with SCD using a standard protocol is safe, with a sedation-related complication rate comparable to that of the general pediatric population. The observed rate of VOE, although not significantly higher than expected, warrants further investigation.