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.

Effect of magnesium sulfate with ketamine infusions on intraoperative and postoperative analgesia in cancer breast surgeries: a randomized double-blind trial

Abstract Background Opioids are the cornerstone in managing postoperative pain; however, they have many side effects. Ketamine and Magnesium (Mg) are NMDA receptor antagonists used as adjuvant analgesics to decrease postoperative opioid consumption. Objective We assumed that adding Mg to ketamine infusion can improve the intraoperative and postoperative analgesic efficacy of ketamine infusion alone in cancer breast surgeries. Methods Ninety patients aged between 18 and 65 years and undergoing elective cancer breast surgery were included in this prospective randomized, double-blind study. Group K received ketamine 0.5 mg.kg-1 bolus then 0.12 mg.kg-1.h-1 infusion for the first 24 hours postoperatively. Group KM: received ketamine 0.5 mg.kg-1 and Mg sulfate 50 mg.kg-1, then ketamine 0.12 mg.kg-1.h-1 and Mg sulfate 8 mg.kg-1.h-1 infusions for the first 24 hours postoperative. The primary outcome was the morphine consumption in the first 24 hours postoperative, while the secondary outcomes were: intraoperative fentanyl consumption, NRS, side effects, and chronic postoperative pain. Results Group KM had less postoperative opioid consumption (14.12 ± 5.11 mg) than Group K (19.43 ± 6.8 mg). Also, Group KM had less intraoperative fentanyl consumption. Both groups were similar in postoperative NRS scores, the incidence of side effects related to opioids, and chronic neuropathic pain. Conclusion Adding Mg to ketamine infusion can safely improve intraoperative and postoperative analgesia with opioid-sparing effect in cancer breast surgery.

Role of melatonin in attenuation of hemodynamic response to intubation and anesthetic requirements: a randomized, controlled, double-blind study

Abstract Background Melatonin has been studied to have anxiolytic, sedative, and analgesic effects. However, there is limited data on the effect of melatonin in the attenuation of hemodynamic response to intubation. We aimed to study whether preanesthetic oral melatonin attenuates hemodynamic responses to intubation and anesthetic requirements. Methods Sixty-four patients scheduled for laparoscopic cholecystectomy were randomized into melatonin or placebo group (n = 32 each). Melatonin group received two tablets (3 mg each) of melatonin, and the placebo group received two tablets of vitamin D3 120 min before induction. Hemodynamic parameters were recorded during induction and postintubation for 15 minutes. Total induction dose of propofol, total intraoperative fentanyl consumption, and adverse effects of melatonin were also noted. Results Postintubation rise in heart rate (HR) was less in the melatonin group compared to the placebo group (10.59% vs. 37.08% at 1 min, respectively) (p< 0.0001). Maximum percentage increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was lesser in melatonin group than placebo group (SBP 9.25% vs. 37.73%, DBP 10.58% vs. 35.51%, MBP 9.99% vs. 36.45% at 1 min postintubation. respectively) (p< 0.0001). Induction dose of propofol (1.42 mg.kg-1 vs. 2.01 mg.kg-1) and the number of patients requiring additional fentanyl intraoperatively (3 vs. 11) were also significantly reduced in the melatonin group. Conclusion Premedication with 6 mg of oral melatonin resulted in significant attenuation of postintubation rise in HR, SBP, DBP, and MBP. It also reduced the induction dose of propofol, total intraoperative fentanyl consumption without any adverse effects.

Eficacia de la analgesia peridural continua con bupivacaína y fentanilo en la cirugía de colon / Efficacy of continuous peridural analgesia with bupivacaine and fentanyl in colon surgery

Introducción: En la cirugía de colon se persigue lograr una recuperación acelerada y se debate el método analgésico más ventajoso. Objetivo: Comparar la eficacia analgésica de la infusión continua peridural con bupivacaína y fentanilo frente a la analgesia parenteral en este tipo de intervención. Métodos: Se realizó un estudio cuasi-experimental, prospectivo y longitudinal, en 30 pacientes operados de colon entre agosto 2018 agosto 2019 en el Hospital Militar Central Dr. Carlos J. Finlay; divididos de forma no aleatoria en grupo analgesia peridural y grupo analgesia multimodal endovenosa. Resultados: La demora en despertar y extubar en el grupo peridural fue inferior (1,6-1,8 min) a los 4,9-5,0 min en el multimodal, igual ocurrió con la estadía en Unidad Cuidados Intensivos Quirúrgicos y hospitalaria aunque con discreta diferencia. El 60 por ciento de los pacientes en el grupo peridural presentaron ruidos hidroaéreos en las primeras 24 h y el 80 por ciento expulsó gases a las 48 h o antes, con marcada diferencia del multimodal. La analgesia fue buena en ambos grupos, valores de escala visual análoga inferiores en el grupo peridural, solo el 13,3 por ciento necesitó dosis rescate frente al 26,7 por ciento en el multimodal. Las complicaciones más frecuentes fueron hipotensión (23,3 por ciento) y bradicardia (10 por ciento), sin diferencias entre grupos. La analgesia aceleró la recuperación en el 87,5 por ciento de los casos en el grupo peridural superior al 76 por ciento del grupo multimodal. Conclusiones: La analgesia peridural continua con bupivacaína y fentanilo es más eficaz que la analgesia multimodal endovenosa en la cirugía de colon y acelera la recuperación posoperatoria(AU)

Introduction: In colon surgery, accelerated recovery is pursued and the most advantageous analgesic method is still under debate. Objective: To compare the analgesic efficacy of continuous epidural infusion with bupivacaine and fentanyl versus parenteral analgesia in this type of operation. Methods: A quasiexperimental, prospective and longitudinal study was carried out with thirty patients who underwent colon surgery, between August 2018 and August 2019 at Dr. Carlos J. Finlay Central Military Hospital, nonrandomly divided into an epidural analgesia group and a multimodal intravenous analgesia group. Results: The awakening and extubation time in the epidural group was lower (1.6 -1.8 min) than the 4.9 to 5.0 min for the multimodal group. The same happened with intensive care unit and hospital stay, although with a discrete difference. 60 percent of the patients from the epidural group presented hydroaerial noise within the first 24 hours and 80 percent expelled gasses at 48 hours or earlier, with a marked difference in the multimodal group. Analgesia was good in both groups, with lower visual analog scale values in the peridural group; only 13.3 percent required rescue doses compared to 26.7 percent in the multimodal group. The most frequent complications were hypotension (23.3 percent ) and bradycardia (10 percent ), without differences between groups. Analgesia accelerated recovery for 87.5 percent of cases in the epidural group, compared to 76 percent in the multimodal group. Conclusions: Continuous epidural analgesia with bupivacaine and fentanyl is more effective than multimodal intravenous analgesia in colon surgery and accelerates postoperative recovery(AU)

Analgosedación con propofol y fentanilo en las colonoscopia / Analgosedation with propofol and fentanyl in colonoscopy

Introducción: La comodidad durante la colonoscopia es una condición importante si se quiere que el paciente acepte procedimientos repetidos. Por lo tanto, se necesita de una buena sedación que pudiera combinar la analgesia con amnesia. Objetivo: Describir la utilidad de la analgosedación balanceada con propofol/fentanilo en colonoscopia ambulatoria. Métodos: Se realizó un estudio observacional descriptivo longitudinal prospectivo en pacientes a los que se les realizó colonoscopia de forma ambulatoria en el Hospital General Universitario Dr. Gustavo Aldereguía Lima en el período entre enero de 2017 y diciembre de 2018. Resultados: El 34,2 por ciento de los pacientes tenía entre 50 y 59 años, el 62,9 por ciento eran mujeres. El 73,3 por ciento de los pacientes se clasificó como ASA II según el estado físico. Los valores medios de frecuencia cardiaca y tensión arterial media tuvieron una disminución ligera después de aplicada la anestesia y se mantuvieron constantes en el resto de los momentos evaluados. Los valores medios de saturación de oxígeno de la hemoglobina se mantuvieron relativamente constantes en todos los momentos y resultaron algo superiores a la llegada del paciente a recuperación. La calidad de la sedación fue adecuada en 86,2 por ciento de los pacientes. La calidad de la analgesia y la recuperación fue buena en 88,4 por ciento y 96,2 por ciento , respectivamente. Se presentaron complicaciones en el 16,5 por ciento de los pacientes. Conclusiones: La analgosedación con propofol y fentanilo resultó una alternativa anestésica de utilidad en los pacientes a los que se les realizó colonoscopia ambulatoria con gran estabilidad hemodinámica en la serie estudiada(AU)

Introduction: Comfort during colonoscopy is an important condition if the patient is expected to accept repeated procedures. Therefore, good sedation that could combine analgesia with amnesia is needed. Objective: To describe the usefulness of balanced analgosedation with propofol/fentanyl in outpatient colonoscopy. Methods: A prospective, longitudinal, descriptive and observational study was carried out with patients who received outpatient colonoscopy at Dr. Gustavo Aldereguía Lima General University Hospital in the period between January 2017 and December 2018. Results: 34.2 percent of the patients were between 50 and 59 years old, while 62.9 percent were women. 73.3 percent of patients were classified as ASA II, according to their physical status. The mean values for heart rate and mean arterial blood pressure had a slight decrease after anesthesia was applied and remained constant for the rest of the evaluated times. The mean values of hemoglobin-oxygen saturation remained relatively constant at all the evaluated times and were slightly higher on the patient's arrival to recovery. The quality of sedation was adequate in 86.2 percent of the patients. The quality of analgesia and recovery was good in 88.4 percent and 96.2 percent, respectively. Complications occurred in 16.5 percent of the patients. Conclusions: Analgosedation with propofol and fentanyl proved to be a useful anesthetic alternative in patients undergoing outpatient colonoscopy, with high hemodynamic stability in the studied series(AU)

Efficacy of opioids and non-opioid analgesics in the treatment of post procedure pain of burned patients: a narrative review

Abstract Introduction Burns are a common trauma that cause acute severe pain in up to 80% of patients. The objective of this narrative review is to evaluate the efficacy of opioids, non-steroidal anti-inflammatory drugs, paracetamol, gabapentinoids, ketamine, and lidocaine in the treatment of acute pain in burn victims. Methodology The databases explored were PubMed, Embase, ClinicalTrials, and OpenGrey. The included randomized, controlled clinical trials assessed the analgesic efficacy of these drugs on hospitalized patients, had no age limit, patients were in the acute phase of the burn injury and were compared to placebo or other analgesic drugs. Studies describing deep sedation, chronic opioid use, chronic pain, and patients taken to reconstructive surgeries were excluded. The Jadad scale was used to evaluate quality. Results Six randomized controlled clinical trials (397 patients) that evaluated the analgesic efficacy of fentanyl (n = 2), nalbuphine (n = 1), ketamine (n = 1), gabapentin (n = 1), and lidocaine (n = 1) to treat post-procedural pain were included. Fentanyl, nalbuphine, and ketamine were effective, while lidocaine was associated with a slight increase in reported pain and gabapentin showed no significant differences. Two studies were of high quality, one was of medium high quality, and three were of low quality. No studies on the efficacy of NSAIDs or paracetamol were found. Conclusion Evidence of efficacy is very limited. Fentanyl, nalbuphine, and ketamine seem to be effective for controlling acute pain in burn patients, whereas gabapentin and lidocaine did not show any efficacy.

Evaluation of lignocaine, dexmedetomidine, lignocaine-dexmedetomidine infusion on pain and quality of recovery for robotic abdominal hysterectomy: a prospective randomized controlled trial

Abstract Background: Acute postoperative pain is associated with poor quality of recovery after surgery. Perioperative use of intravenous lignocaine or dexmedetomidine have demonstrated better pain control, early return of bowel function, and effects on quality of recovery. Methods: Ninety-six women planned for elective robotic abdominal hysterectomy were randomized into four groups. Groups received lignocaine infusion (1.5 mg.kg−1 loading, 2 mg.kg−1.h−1 infusion) (Group I), dexmedetomidine infusion (1 µg.kg−1 loading, 0.6 µg.kg−1.h−1 infusion) (Group 2), lidocaine (1.5 mg.kg−1 loading, 2 mg.kg−1.h−1 infusion), and dexmedetomidine infusions (1 µg.kg−1 loading, 0.5 µg.kg−1.h−1 infusion) (Group 3), and normal saline 10 mL loading, 1 mL.kg−1.h−1 infusion) (Group 4). Primary outcome was visual analogue pain scores at 1, 2, 4, 12, and 24 hours after surgery. Secondary outcomes included postoperative fentanyl requirement, time of return of bowel sounds and flatus, QoR15 score on day 1, 2, and discharge. Results The VAS was significantly lower in Groups 2 and 3 compared to Groups 1 and 4. Total postoperative fentanyl consumption in the first 24 hours was 256.25 ± 16.36 mcg (Group 1), 177.71 ± 16.81 mcg (Group 2), 114.17 ± 16.19 mcg (Group 3), and 304.42 ± 31.26 mcg (Group 4), respectively. Time to return of bowel sounds and passage of flatus was significantly shorter in Groups 2 and 3 (p < 0.01). QoR15 scores after surgery were higher in Group 3 compared to Groups 1, 2, and 4, (p < 0.01) respectively. Conclusion: Combined infusion of lignocaine and dexmedetomidine significantly decreased postoperative pain, fentanyl consumption, and improved quality of recovery score after surgery in patients undergoing Robotic abdominal hysterectomy.

Comparative study between S-(+)-ketamine­midazolam and fentanyl­droperidol in black-tufted marmosets (Callithrix penicillata) / Estudo comparativo entre S-(+)cetamina-midazolam e fentanil-droperidol em saguis-de-tufo-preto (Callithrix penicillata)

Sedative and antinociceptive effects of two anesthetic protocols in black-tufted marmosets were compared in this study. Twenty-six marmosets underwent chemical immobilization for physical examination, blood sampling, tattooing, and microchipping. Animals were randomly treated with S-(+)-ketamine (10 mg/kg) and midazolam (1 mg/kg) (KM) or fentanyl (12.5 µg/kg) and droperidol (625 µg/kg) (FD) given by intramuscular injection. Heart and respiratory rates were recorded. Sedation, antinociception, muscle relaxation, posture, auditory, and visual responses were evaluated using a scoring system. Sedation in KM was achieved faster (p < 0.001) and lasted for a shorter period of time (p = 0.0009). KM was similar to FD in its cardiorespiratory effects, auditory and visual responses. Both protocols promoted adequate sedation to allow manipulation. Animals in KM assumed lateral recumbency while animals in FD maintained a quadrupedal posture during evaluation. FD produced less intense sedation and muscle relaxation but a higher degree of antinociception compared to KM and is suitable for procedures that require analgesia in black-tufted marmosets.(AU)

O presente estudo comparou os efeitos cardiorrespiratórios, sedativos e antinociceptivos de dois protocolos anestésicos em saguis-de-tufo-preto (Callithrix penicillata). Vinte e seis saguis foram submetidos à contenção química para exame físico, coleta de sangue, tatuagem de identificação e microchip. Os animais foram tratados aleatoriamente com a associação de S-(+)-cetamina (10 mg/kg) e midazolam (1 mg/kg) (KM) ou fentanil (12,5 µg/kg) e droperidol (625 µg/kg) (FD), administrados por injeção intramuscular. Foram avaliadas frequência cardíaca, frequência respiratória, sedação, antinocicepção, relaxamento muscular, postura e resposta ao estímulo auditivo e visual. A sedação em KM foi alcançada mais rapidamente (p <0,001) e teve um tempo hábil mais curto (p = 0,0009). KM foi semelhante a FD nos efeitos cardiorrespiratórios, respostas auditivas e visuais. Os dois protocolos promoveram sedação adequada para manipulação. Os animais do grupo KM permaneceram em decúbito lateral durante a avaliação, enquanto os animais em FD mantiveram postura quadrupedal. FD resultou em sedação e relaxamento muscular de menor intensidade, porém com maior escore de antinocicepção em comparação com KM, sendo adequada para procedimentos que requerem analgesia em saguis-de-tufo-preto.(AU)

A meta-analysis on the effectiveness of postoperative analgesia with intrathecal nalbuphine versus intrathecal fentanyl as neuraxial adjuvants in cesarean section

@#<p><strong>Background: </strong>Inadequately treated postoperative pain can contribute significantly to morbidity in women undergoing cesarean section.  Recent studies showed that nalbuphine and fentanyl has promising result as neuraxial adjuvants in terms of postoperative analgesia and with lower incidents of adverse effect when use in cesarean section. </p><p><strong>Objective: </strong>To determine the effectiveness of postoperative analgesia with intrathecal nalbuphine versus intrathecal fentanyl as neuraxial adjuvants in cesarean section. </p><p><strong>Methods</strong>:  A meta-analysis following the PRISMA guidelines was performed.  Articles were searched through the Cochrane Library, PubMed.Gov and Pubmed Central, Google Scholar, HERDIN, WPRIM and ProQuest Guideline Central using different search strategies such as keywords and MeSH term.  Cochrane version 2 risk-of-bias tool for randomized trials (RoB 2) was used to assess for quality.  Quantitative data were pooled and analyzed using Review Manager 5.4. </p><p><strong>Results: </strong>A total of four trials, involving 425 full term pregnant women were analyzed. The pooled mean difference showed significantly longer duration of postoperative analgesia (MD=21.12 minutes, 95%CI=11.13,31.11, I2=73%), pooled risk ratio showed lesser risk for pruritus (RR=0.09, 95%CI=0.02,0.50, I2 = 0%) and postoperative nausea and vomiting (RR=0.38, 95%CI= 0.19,0.78, I2 = 11%) who received intrathecal nalbuphine compared to intrathecal fentanyl. </p><p><strong>Conclusions</strong>: The results of this meta-analysis demonstrates that the use of intrathecal nalbuphine appears to have a better outcome in increasing the duration of postoperative analgesia and with lesser incidence of PONV and pruritus than fentanyl.  However, due to the presence of heterogeneity it warrants that the results should be treated with caution especially with the possibility of publication bias. </p><p><strong>Recommendations: </strong>Better literature search through inclusion of high-quality studies from relevant databases and strict adherence on the uniformity of the dosage and <strong>methods</strong> used are very crucial to achieve the target clinical outcomes and minimize the publication bias. </p>

Quadratus Lumborum Block for Upper Tract Urological Surgery in Pediatric Patients / Bloqueo del cuadrado lumbar para cirugía urológica del tracto superior en pacientes pediátricos

Objective Among regional blocks, the quadratus lumborum fascial plane block (QLB) has been well described, but the description of its use and efficacy for pediatric patients undergoing upper abdominal urologic surgery is limited. We present a case series examining the use of the QLB for postoperative pain management in children undergoing upper tract surgery. Methods From August 2019 to August 2020, through a chart review, we identified 5 patients who had undergone a QLB for upper urinary tract surgery via a flank incision. Posterior QLB was performed after induction of general anesthesia. A single injection of 0.5mL/kg of either 0.25% or 0.5% ropivacaine with 1mcg/kg of clonidine was administered. Patients received fentanyl IV (1 mcg/kg), and acetaminophen IV (15mg/kg) as adjuvants during the operation. Postoperative pain was managed with oral acetaminophen and ibuprofen. Results The average postoperative pain score during the entire admission was 1, with the lowest being 0 and highest, 3. No administration of rescue narcotics was required in the postanesthesia care unit or on the floor. The average length of stay ranged from 0 to 1 day. No complications associated with the regional QLB were identified. Conclusions Our series suggests the QLB may be considered as a regional anesthetic option to minimize narcotic requirements for children undergoing upper abdominal urological surgery via flank incision. Additional studies are needed to compare the efficacy of the QLB versus alternate regional anesthetic blocks for upper tract urological surgery via flank incision in children and to determine effective dosing and use of adjuvants

Objetivo Entre los bloqueos regionales, el bloqueo del plano fascial del cuadrado lumbar (BCL) ha sido bien descrito; sin embargo, tiene una descripción limitada de su uso y eficacia en pacientes pediátricos sometidos a cirugía urológica abdominal superior. Presentamos una serie de casos que examinan el uso del BCL en el manejo del dolor posoperatorio en niños sometidos a cirugía urológica del tracto superior. Métodos De agosto de 2019 a agosto de 2020, mediante revisión de historias clínicas, se identificaron 5 pacientes sometidos al BCL para cirugía del tracto urinario superior por incisión en el flanco. El BCL posterior se realizó después de la inducción de la anestesia general. Solo se administró una inyección de 0,5 ml/kg de ropivacaína al 0,25% o al 0,5% con 1 mcg/kg de clonidina. Los pacientes recibieron fentanilo IV (1 mcg/kg) y acetaminofén IV (15 mg/kg) como adyuvantes durante la operación. El dolor posoperatorio se manejó con acetaminofén e ibuprofeno oral. Resultados El puntaje promedio de dolor posoperatorio para todo el ingreso fue de 1, siendo el más bajo 0 y el más alto, 3. No se requirieron administraciones de narcóticos de rescate en la unidad de recuperación posanestésica ni en la planta de hospitalización. La estancia media fue de 0 a 1 día. No se identificaron complicaciones asociadas con el BCL regional. Conclusiones Nuestra revisión sugiere que el BCL puede ser considerado una opción anestésica regional para minimizar los requerimientos de narcóticos en niños sometidos a cirugía urológica abdominal superior por incisión en el flanco. Se necesitan estudios adicionales para comparar la eficacia de BCL en comparación con la de los bloqueos anestésicos regionales alternativos para la cirugía urológica del tracto superior por incisión en el flanco en niños y para determinar la efectividad de la dosificación y del uso de adyuvantes.

Exploración de la eficacia analgésica de dos parches transdérmicos analgésicos de opioides, buprenorfina y fentanilo, según sus variaciones de dosis en el control del dolor en pacientes paliativos oncológicos / Exploration of the analgesic efficacy of two-transdermal analgesic patches of opioids, buprenorphine and fentanyl, according to their dose variations in pain control in palliative cancer patients

Objetivo: El presente trabajo de investigación tuvo como objetivo explorar la eficacia analgésica mediante la comparación de la respuesta analgésica de los parches transdérmicos (PTD) de buprenorfina y fentanilo en dolor oncológico y patrón de uso. Material y Método: Se obtuvieron los datos y variables desde los registros clínicos de pacientes ingresados a la Unidad de Cuidados Paliativos (UCP) del Instituto Nacional del Cáncer (INC) que estaban bajo tratamiento en mayo del 2017. Se incluyó en este estudio a 78 pacientes con PTD, que representan el 13% de los pacientes en control mensual. De estos, 66 estaban bajo tratamiento con buprenorfina y 8 bajo tratamiento con fentanilo. Resultados: Los resultados mostraron que el PTD de buprenorfina se utiliza más frecuentemente que el de fentanilo. El principal motivo de rotación fue dolor no controlado, seguido por imposibilidad de contar con la administración por vía oral. En pacientes con mayores intensidades de dolor somático o visceral se indicó fentanilo y en aquellos con componente neuropático se prefirió el uso de buprenorfina. PTD de fentanilo fue indicado en dosis mayores que buprenorfina, incluso al comparar sus dosis equianalgésicas, siendo la variación de dosis alta para ambos parches: aumentó en promedio 257%. Se logró una mejor respuesta analgésica con buprenorfina, con una variación de intensidad de escala numérica verbal (ENV) de 2,94 y 1,88 puntos de promedio para buprenorfina y fentanilo, respectivamente. Adicionalmente, se presentó mayor reacción local dérmica con fentanilo. Conclusiones: Se evidenció diferencias en patrón de uso y, a diferencia de lo esperado, se obtuvo una mejor eficacia analgésica con buprenorfina. Datos que deben ser corroborados en estudios con mayor número de pacientes bajo tratamiento con fentanilo.

Objective: This study aims to explore analgesic efficacy comparisons of buprenorphine and fentanyl transdermal patches (TDP) in cancer pain and it's usage pattern. Material and Method: Data and variables were collected from patient's clinical reports who were admitted in the National Cancer Institute's (NCI) Palliative Care Unit (PCU) and were under treatment with TDP in May 2017. 78 TDP patients were studied and represented 13% of the monthly control patients in the PCU. Of these, 66 were under buprenorphine treatment and 8 under fentanyl treatment. Results: The results showed that buprenorphine TDP is more frequently used than fentanyl TDP, and the main reason for exchange between them was uncontrolled pain, followed by oral administration impossibility. Fentanyl TDP was indicated in patients with higher somatic or visceral pain intensities and Buprenorphine TDP was preferred in patients with neuropathic pain. Fentanyl TDP was indicated in higher doses than buprenorphine, even when comparing its equianalgesic doses, the dose variation was high for both patches throughout the treatment: it increased on average by 257%. A better analgesic response was achieved with buprenorphine, with a variation of intensity of the Verbal Numerical Scale (VNS) of 2.94 and 1.88 average points, for buprenorphine and fentanyl respectively. Additionally, there was a higher local dermal reaction with fentanyl TDP. Conclusions: Differences in usage patterns were evidenced and, unlike what was expected, better analgesic efficacy was obtained with buprenorphine TDP. This data should be corroborated in receiving fentanyl treatment.

¿Puede el fentanilo intratecal disminuir la aparición de náuseas y vómito en comparación con ondansetrón intravenoso durante cesárea electiva? Revisión sistemática de la literatura y metaanálisis / Can intrathecal fentanyl decrease the occurrence of nausea and vomiting compared with intravenous ondansetron during elective cesarean section? Literature Systematic review and meta-analysis

Elective caesarean section is one of the surgeries with the highest intraoperative incidence of nausea, retching and vomiting (IONV), due, among other causes, to the use of anesthetics during the procedure. Some clinical trials have associated the use of low-dose intrathecal (IT) fentanyl with a lower incidence of nausea, retching and vomiting compared to other anesthetics used during caesarean sections. In this context, the objective of this meta-analysis was to evaluate the decrease in the appearance of nausea and vomiting during elective caesarean section with the application of IT fentanyl when compared with the use of intravenous ondansetron (EV). A systematic search was conducted in the main databases (PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library and Google Scholar) for Randomized Clinical Trials (RCTs) that evaluated the use of IT fentanyl compared to ondansetron EV to decrease the occurrence and incidence of IONV during elective caesarean section. The meta-analysis showed a reduction in the incidence of nausea (RR 0.52, 95% CI 0.29-0.93, P = 0.03), gagging (RR 0.39, 95% CI 0, 18-0.88, P = 0.02) and vomiting (RR 0.26, 95% CI 0.11-0.64, P = 0.003) in the group of patients treated with IT fentanyl compared to the group treated with EV ondansetron. From the results, it is suggested that the administration of 12.5 to 20 µg of IT fentanyl may decrease the incidence of IONV in patients undergoing elective caesarean section, although the importance of more high-quality RCTs is highlighted.

La cesárea electiva es una de las cirugías con mayor incidencia intraoperatoria de náuseas, arcadas y vómito (NAV), debido entre otras causas, al uso de anestésicos durante el procedimiento. Algunos ensayos clínicos han asociado el uso de fentanilo intratecal (IT) a dosis bajas con una menor incidencia de náuseas, arcadas y vómito en comparación con otros anestésicos usados durante las cesáreas. En este contexto el objetivo de este metaanálisis fue evaluar la disminución en la aparición de náuseas y vómito durante cesárea electiva con la aplicación de fentanilo IT al compararlo con el uso de ondansetrón intravenoso (EV). Se realizó una búsqueda sistemática en las principales bases de datos (PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library y Google Scholar) para ensayos clínicos aleatorizados (ECA) que evaluaron el uso del fentanilo IT en comparación con ondansetrón EV para disminuir la aparición e incidencia de IONV durante cesárea electiva. En el metaanálisis se evidenció una reducción en la incidencia de náusea (RR 0,52, 95% IC 0,29-0,93, P = 0,03), arcada (RR 0,39, 95% IC 0,18-0,88, P = 0,02) y vómito (RR 0,26, 95% IC 0,11-0,64, P = 0,003) en el grupo de pacientes tratados con fentanilo IT comparado con el grupo tratado con ondansetrón EV. A partir de los resultados, se sugiere que la administración de 12,5 a 20 µg de fentanilo IT puede disminuir la incidencia de NAV intraoperatorias en pacientes sometidas a cesárea electiva, aunque se resalta la importancia de más ECA de alta calidad.

Bloqueo caudal más anestesia general balanceada en un paciente con pentalogía de Cantrell, presentación de un caso clínico / Caudal block plus inhaled general anesthesia in a patient with pentalogy of Cantrell, presentation of a clinical case

The pentalogy of Cantrell is a disorder characterized by congenital abnormalities in the abdominal wall, lower sternum, anterior diaphragm, diaphragmatic pericardium, and cardiac anomalies. It is a rare disease with 250 cases registered around the world. The anesthetic implications will require a specialized management given the ventilatory mechanics and cardiac function which are compromised by the disease in the newborn. We present the case of a female patient with pentalogy of Cantrell without prenatal diagnosis, who had an operative procedure to correct patent ductus arteriosus and abdominal mesh placement under balanced general anesthesia with sevoflurane and fentanyl plus caudal block. This case is reported to provide our experience in the anesthetic management of this type of patients.

La pentalogía de Cantrell es una enfermedad caracterizada por anormalidades congénitas de la pared abdominal supraumbilical, esternón inferior, diafragma, pericardio diafragmático y anomalías cardiacas. Se trata de una enfermedad rara con 250 casos registrados alrededor del mundo. Las implicaciones anestésicas requieren de un manejo especializado debido a la mecánica ventilatoria y función cardíaca que se encuentran comprometidas en el recién nacido. Se presenta el caso de una recién nacida portadora de pentalogía de Cantrell, no diagnosticada prenatalmente, quien fue sometida a corrección de ductus arterioso persistente y colocación de malla abdominal bajo anestesia general balanceada con sevofluorano y fentanilo más bloqueo caudal. Se reporta el presente caso para brindar nuestra experiencia en el manejo anestésico de este tipo de pacientes.

Fentanyl attenuates air-puff stimulus-evoked field potential response in the cerebellar molecular layer via inhibiting interneuron activity in mice / 生理学报

Fentanyl as a synthetic opioid works by binding to the mu-opioid receptor (MOR) in brain areas to generate analgesia, sedation and reward related behaviors. As we know, cerebellum is not only involved in sensory perception, motor coordination, motor learning and precise control of autonomous movement, but also important for the mood regulation, cognition, learning and memory. Previous studies have shown that functional MORs are widely distributed in the cerebellum, and the role of MOR activation in cerebellum has not been reported. The aim of the present study was to investigate the effects of fentanyl on air-puff stimulus-evoked field potential response in the cerebellar molecular layer using in vivo electrophysiology in mice. The results showed that perfusion of 5 μmol/L fentanyl on the cerebellar surface significantly inhibited the amplitude, half width and area under the curve (AUC) of sensory stimulation-evoked inhibitory response P1 in the molecular layer. The half-inhibitory concentration (IC

Comparison of post-anesthesia recovery time in sedated patients for colonoscopy using midazolam or fentanyl associated with propofol / Comparação do tempo de recuperação pós-anestésica em pacientes sedados para colonoscopia usando midazolam ou fentanil associados a propofol

ABSTRACT Objective: Comparison of post-anesthesia recovery time in sedated patients for colonoscopy using two drug combinations: midazolam and propofol or fentanyl and propofol. Method: Fifty patients ASA I and II, from 18 to 65 years of age, candidates for elective colonoscopy under sedation administered by an anesthesiologist, were randomized in two groups: Group A (midazolam and propofol) and Group B (fentanyl and propofol). Each patient was evaluated as for the length of the exam (Exam length), length of stay in the post-anesthesia care unit 1 and 2 (LSPACU1 and LSPACU2) and hospital discharge. Episodes of awakening, and of movement, drop in SpO2 < 90%, need for mechanical ventilation, propofol consumption, heart rate (HR) and mean blood pressure (MBP) were also evaluated. Results: Patients of group B had a recovery time in LSPACU1 statistically shorter than that for those in group A. In both groups, LSPACU1 was considered inversely proportional to LSPACU2. Hospital discharge time was similar between groups. Patients of group B had a significant decrease in MBP during and at the end of the exam, when compared to the initial measurement and that during sedation. Nevertheless, this variation was lower than 20%. No adverse event was observed. All patients were discharged on the same day, with no unexpected hospitalization. Conclusions: The combined use of fentanyl and propofol for colonoscopy sedation had a post-anesthesia recovery time in LSPACU1 shorter than that with the combination of midazolam and propofol. Nevertheless hospital discharge time was similar between groups.

RESUMO Objetivo: Comparar o tempo de recuperação pós-anestésica de pacientes sedados para colonoscopia usando duas combinações de fármacos: midazolam e propofol ou fentanil e propofol. Método: Cinquenta pacientes ASA I e II, entre 18 e 65 anos, candidatos a colonoscopia eletiva sob sedação administrada por anestesiologista, foram randomizados em dois grupos: Grupo A (midazolam e propofol) e Grupo B (fentanil e propofol). Cada paciente foi avaliado quanto ao tempo de realização do exame (TExame), tempo de permanência na sala de recuperação pós-anestésica 1 e 2 (TSRPA 1 e TSRPA2) e a alta domiciliar. Episódios de despertar, movimentação, queda de SpO2 < 90%, necessidade de assistência ventilatória, consumo de propofol, frequência cardíaca (FC) e pressão arterial média (PAM) também foram avaliados. Resultados: Pacientes do grupo B apresentaram tempo de recuperação na SRPA1 inferior estatisticamente ao grupo A. Em ambos os grupos o TSRPA1 foi considerado inversamente proporcional ao TSRPA2. O tempo de alta domiciliar foi semelhante entre os grupos. Pacientes do grupo B apresentaram redução significativa na PAM no tempos exame e final, em relação ao inicial e sedação. Entretanto, essa variação foi inferior a 20%. Não foram observados eventos adversos. Todos os pacientes evoluíram com alta domiciliar no mesmo dia, sem ocorrência de internação não prevista. Conclusões: O uso combinado de fentanil e propofol para sedação em colonoscopia produziu tempo de recuperação pós-anestésica na SRPA1 inferior a combinação midazolam e propofol. No entanto, o tempo de alta domiciliar foi semelhante entre os grupos.

Experiencia en sedoanalgesia vinculada a procedimientos en un departamento de emergencia pediátrica / Experience in procedural sedation and analgesia in a pediatrics emergency unit / Experiência em sedação e analgesia ligada a procedimentos em um departamento de emergência pediátrica

Resumen: Introducción: la realización de procedimientos dolorosos es cada vez más frecuente en el área de urgencias pediátricas. El control del dolor, mitigar el temor y la ansiedad es una pieza clave en la atención del paciente pediátrico y una de las prioridades del médico emergencista. Objetivo: describir la experiencia en sedoanalgesia con ketamina y fentanilo como único fármaco o asociados a otros para procedimientos dolorosos en el Departamento de Emergencia Pediátrica (DEP) del Centro Hospitalario Pereira Rossell (CHPR). Material y método: estudio descriptivo, retrospectivo. Período: enero de 2011 a julio de 2016. Población: todos los pacientes que recibieron sedoanalgesia con ketamina o fentanilo (solos o asociado a otros fármacos) para realización de procedimientos dolorosos en el DEP-CHPR. Base de datos: historias clínicas. Se midió la eficacia mediante el éxito del procedimiento y la seguridad por la presencia de efectos adversos vinculados a la misma. Resultados: n=352, menores de 15 años; 96 recibieron ketamina y 256 recibieron fentanilo. Media de edad: 7 años, sexo masculino: 245. Dosis media de ketamina 1 mg/kg. Dosis media de fentanilo 1 ɤ/kg. Principales indicaciones de sedoanalgesia: procedimientos ortopédicos (264), toracocentesis (62). Procedimiento con éxito: 352 pacientes. Monitorización cardiovascular y saturometría durante el procedimiento: 100%. Efectos adversos: seis (no requiriendo maniobras de soporte vital avanzado). Ningún paciente cambió su destino final. Conclusiones: la utilización de sedoanalgesia resultó eficaz y segura realizada por el pediatra emergencista capacitado en el manejo farmacológico y de soporte vital avanzado. La monitorización del procedimiento durante y luego de éste es necesaria para pesquisar y resolver precozmente las complicaciones.

Summary: Introduction: painful procedures are gradually increasing frequency in pediatrics emergency units. Controlling pain and mitigating fear and anxiety are of the essence when assisting pediatric patients and one of the priorities of emergency doctors. Objective: to describe using sedoanalgesia with ketamine and fentanyl as the only drug or associated with other drugs during painful procedures, at the Pediatrics Emergency Unit, of the Pereira Rossell Hospital Center. Method: descriptive, retrospective study from January 2011 to July 2016. Population: all patients who received sedoanalgesia with ketamine and fentanyl (as the only drug or associated with other drugs) during painful procedures at the Pediatrics Emergency Unit, of the Pereira Rossell Hospital Center. Database: medical records. Effectiveness was measured by success of the procedure and safety in terms of adverse effects in connection with it. Results: N=352 children younger than 15 years old. 96 received ketamine and 256 received fentanyl. Average age was 7 years old and 245 of them were boys. Average dose of ketamine was 1 mg/kg, average dose of fentanyl was 1 ɤ/kg. Main indications for sedoanalgesia included: orthopaedic procedures (264), thoracentesis (62). Procedures were successful in 352 patients. 100% of cases involved cardiovascular monitoring and blood oxygen saturation meter. Adverse effects: 6 (no advanced life support manoeuvres required). No patient changed final destination. Conclusions: the use of sedoanalgesia was effective and safe, when applied by emergengy pediatricians qualified in the handling of drugs and advanced life support. Monitoring during and after procedure is required to determine and solve complications at an early stage.

Resumo Introdução: a realização de procedimentos dolorosos é cada vez mais frequente na área de emergência pediátrica. Controlar a dor, mitigar o medo e a ansiedade é um elemento-chave no atendimento ao paciente pediátrico e uma das prioridades do médico de emergência. Objetivo: descrever a experiência em sedação e analgesia com ketamina e fentanil como fármaco único ou associado a outros para procedimentos dolorosos, no Serviço de Emergência Pediátrica (DEP) do Centro Hospitalar Pereira Rossell (CHPR) Material e métodos: estudo descritivo retrospectivo. Período: janeiro de 2011 a julho de 2016. População: todos os pacientes que receberam sedação e analgesia com ketamina ou fentanil (isoladamente ou em combinação com outras drogas) para realização de procedimentos dolorosos no DEP-CHPR. Banco de dados: prontuários médicos. A eficácia foi medida pelo sucesso do procedimento e a segurança pela presença de efeitos adversos associados. Resultados: n = 352 crianças menores de 15 anos. 96 receberam ketamina e 256 receberam fentanil. Idade média: 7 anos, sexo masculino: 245. Dose média de ketamina 1 mg / kg. Dose média de fentanil 1 ɤ/kg. Principais indicações para sedação e analgesia: procedimentos ortopédicos (264), toracocentese (62). Procedimento com sucesso: 352 pacientes. Monitorização cardiovascular e oximetria durante o procedimento: 100%. Efeitos adversos: 6 (não requer manobras de suporte avançado de vida). Nenhum paciente mudou seu destino final. Conclusões: o uso da sedação e analgesia foi eficaz e seguro realizado por pediatra de emergência capacitado em manejo farmacológico e suporte avançado de vida. O monitoramento do procedimento durante e após é necessário para investigar e resolver precocemente as complicações.

Síndrome serotoninérgico como reacción adversa infrecuente ante la sinergia entre Linezolid y Fentanilo: presentación de caso / Serotonin syndrome as an infrequent adverse reaction to synergy between Linezolid and Fentanyl: case presentation

Resumen El síndrome serotoninérgico es una condición potencialmente mortal causada por medicamentos que afectan el metabolismo de la serotonina o que actúan como agonistas directos del receptor de esta o una combinación de ambos. El síndrome da lugar a una variedad de manifestaciones mentales, autonómicas y neuromusculares, que pueden variar desde leves hasta potencialmente mortales. Se reporta el caso clínico de un paciente el cual desarrolló este síndrome por la coadministración y sinergismo de linezolid y fentanilo, con una gran variedad de características clínicas, desde las más sutiles, como cifras tensionales altas de difícil manejo mientras se encontraba bajo el efecto de sedoanalgesia, hasta las manifestaciones más floridas del síndrome posterior a la suspensión de esta. La asociación de estos medicamentos representa una etiología poco informada que puede favorecer la aparición del síndrome, mientras que el uso de benzodiazepinas puede enmascarar el cuadro dificultando su diagnóstico. MÉD.UIS.2020;33(3): 59-66

Abstract Serotonin syndrome is a life-threatening condition caused by medications that affect serotonin metabolism or that act as direct agonists for serotonin receptor or a combination of both. The syndrome gives rise to a variety of mental, autonomic, and neuromuscular manifestations, which can range from mild to life-threatening. We report a clinical case of a patient who developed this syndrome due to the co-administration and synergism of linezolid and fentanyl, with a wide variety of clinical characteristics, from the most subtle, such as high blood pressure levels difficult to manage while under the effect of sedoanalgesia, to the most florid manifestations of the syndrome after 48 hours of its suspension. The association of these drugs represents a poorly reported etiology that may favor the appearance of the syndrome, while the use of benzodiazepines may mask the condition, making its diagnosis difficult. MÉD.UIS.2020;33(3): 59-66

Anestesia total intravenosa con remifentanilo vs fentanilo como base analgésica en cirugía torácica electiva / Intravenous total anesthesia with remifentanil and fentanyl as analgesic base in elective thoracic surgery

Introducción: Mantener una oxigenación adecuada durante la ventilación a un solo pulmón es el problema fundamental al que se enfrenta el anestesiólogo durante la cirugía torácica, es por ello que se mantiene una constante búsqueda del método anestésico ideal que ayude a lograr dicho objetivo. Objetivos: Evaluar los resultados de dos técnicas de anestesia total intravenosa con remifentanilo y fentanilo como base analgésica e identificar la aparición de complicaciones durante la intervención quirúrgica. Métodos: Se realizó un estudio causiexperimental prospectivo, en el Hospital Docente Clínico Quirúrgico Dr. Salvador Allende, entre enero 2013 a diciembre 2015 en 40 pacientes ASA II o III que requirieron procedimientos intratorácicos. Estos se dividieron en dos grupos. A (remifentanilo-propofol) y B (fentanilo-propofol). Se estudiaron variables hemodinámicas, de oxigenación durante la ventilación unipulmonar, el tiempo de recuperación anestésica (ventilación espontánea, apertura ocular, extubación) y la analgesia posoperatoria. Resultados: No existieron variaciones significativas en la hemodinamia, ni en la oxigenación de los enfermos con el empleo de ambas técnicas anestésicas; sin embargo, el despertar y recuperación posoperatoria a corto plazo fue mejor en el grupo A. La intensidad del dolor posoperatorio según la escala visual análoga fue menor en el grupo B. Conclusiones: Ambas técnicas son efectivas para procedimientos quirúrgicos torácicos. Con mínima interferencia en la hemodinámia y parámetros de oxigenación(AU)

Introduction: Maintaining adequate oxygenation during single-lung ventilation is a fundamental concern faced by the anesthesiologist during thoracic surgery; therefore, a constant search is maintained for the ideal anesthetic method that helps achieve this goal is maintained. Objectives: To evaluate the outcomes of two total intravenous anesthesia techniques with remifentanil and fentanyl as analgesic base and to identify the onset of complications during surgery. Methods: A prospective and quasi-experimental study was carried out at Dr. Salvador Allende Clinical-Surgical Hospital, between January 2013 and December, with 40 ASA II or III patients who required intrathoracic procedures. These were divided into two groups: A (remifentanil-propofol) and B (fentanyl-propofol). Hemodynamic variables and others of oxygenation during one-lung ventilation were studied, together with anesthetic recovery time (spontaneous ventilation, ocular opening, extubation) and postoperative analgesia. Results: There were no significant variations in the hemodynamics or oxygenation of patients with the use of both anesthetic techniques; however, awakening and short-term postoperative recovery was better in group A. Postoperative pain intensity, based on the analogue-visual scale, was lower in group B. Conclusion: Both techniques are effective for thoracic surgical procedures, with minimal effect in hemodynamics and oxygenation parameters(AU)

Antimicrobial effects of fentanyl and bupivacaine: an in vitro study / Efeitos antimicrobianos do fentanil e da bupivacaína: estudo in vitro

Abstract Study objective: In this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case of combined use. Design: In vitro prospective study. Setting: University Clinical Microbiology Laboratory. Measurements: In our study, in vitro antimicrobial effect of 0.05 mg.mL-1 fentanyl citrate, 5 mg.mL-1 bupivacaine were tested against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231 as Group F (Fentanyl Citrate) and Group B (Bupivacaine), respectively. S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 25922 were cultured onto Mueller Hinton agar (Oxoid, UK) plates and Candida albicans ATCC 10231 were cultured onto Sabouraud dextrose agar (Oxoid, UK) plates for 18-24 hours at 37 °C. Main results: In terms of inhibition zone diameters, S. Aureus ATCC 29213, P. aeruginosa ATCC 27853, and C. albicans ATCC10231 values obtained after 12 and 24 hours of incubation ​​were significantly higher in Group F than Group B (p < 0.001). In terms of inhibition zone diameters, E. coli ATCC 25922, and K. pneumomiae ATCC 13883 values obtained after 12 and 24 hours of incubation ​​were significantly higher in Group B than Group F (p < 0.001, E. coli 12ª hour p = 0.005). Conclusions: Addition of fentanyl to Local Anesthetics (LAs) is often preferred in regional anesthesia applications in today's practice owing especially to its effect on decreasing the local anesthetic dose and increasing analgesia quality and patient satisfaction. However, when the fact that fentanyl antagonized the antimicrobial effects of LAs in the studies is taken into account, it might be though that it contributes to an increase in infection complications. When the fact that fentanyl citrate which was used in our study and included hydrochloric acid and sodium hydroxide as protective agents, broadened the antimicrobial effect spectrum of LAs, had no antagonistic effect and showed a synergistic antimicrobial effect against E. Coli is considered, we are of the opinion that the addition of fentanyl to LAs would contribute significantly in preventing the increasing regional anesthesia infection complications.

Resumo Objetivo: O objetivo do presente estudo foi comparar os efeitos antimicrobianos da bupivacaína e citrato de fentanil e revelar o impacto no potencial do efeito antimicrobiano no caso de uso combinado. Desenho: Estudo prospectivo in vitro. Local: Laboratório de Microbiologia Clínica da Universidade. Medidas: Em nosso estudo, os efeitos antimicrobianos in vitro do citrato de fentanil na concentração de 0,05 mg.mL-1 - Grupo F e da bupivacaína na concentração de 5 mg.mL-1 - Grupo B foram testados em culturas de Staphylococcus aureus ATCC 29213 (do inglês American Type Culture Collection 29213), Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 e Candida albicans ATCC 10231. As culturas de S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 e Escherichia coli ATCC 25922 foram semeadas em placas de ágar Mueller Hinton (Oxoid, Reino Unido), e a cultura de Candida albicans ATCC 10231 foi realizada em placa de ágar Sabouraud dextrose (Oxoid, Reino Unido) durante 18-24 horas a 37 °C. Principais resultados: Com relação ao diâmetro da zona de inibição, os valores de S. aureus ATCC 29213, P. aeruginosa ATCC 27853 e C. albicans ATCC10231 obtidos após 12 e 24 horas de incubação foram significantemente maiores no Grupo F do que no Grupo B (p < 0,001). Os valores do diâmetro da zona de inibição das culturas de E. coli ATCC 25922 e K. pneumomiae ATCC 13883 obtidos após 12 e 24 horas de incubação foram significantemente maiores no Grupo B do que no Grupo F (p < 0,001, E. coli na 12ª hora p = 0,005) Conclusões: A preferência atual e frequente pela adição de fentanil aos Anestésicos Locais (AL) para a realização de anestesia regional se deve sobretudo à possibilidade de redução da dose do anestésico local, a melhora na qualidade da analgesia e a satisfação do paciente. No entanto, ao considerar estudos em que o fentanil antagonizou o efeito antimicrobiano dos AL, pode-se pensar que esse fato contribua para aumento de complicação infecciosa. O citrato de fentanil usado em nosso estudo, contendo ácido clorídrico e hidróxido de sódio como agentes conservantes, ampliou o espectro de efeitos antimicrobianos dos AL, não teve efeito antagônico e demonstrou efeito antimicrobiano sinérgico contra a E. coli. Acreditamos que a adição de fentanil aos anestésicos locais traria importante contribuição na prevenção das crescentes complicações por infecção da anestesia regional.

Uso de dexmedetomidina comparado con lidocaína y fentanilo para destete de ventilación mecánica en pacientes con COVID-19 / Use of dexmedetomidine compared with lidocaine and fentanyl for weaning from mechanical ventilation in COVID-19 patients

INTRODUCCIÓN: Uno de los mayores intereses en el campo de la salud y en torno a la pandemia de COVID-19 es el desarrollo de estrategias para reducir la transmisión de la infección por SARS-CoV-2, incluyendo la protección de los trabajadores de salud, grupo de riesgo frente a la infección por este virus (Ng et al. 2020). La extubación es un procedimiento generador de aerosoles debido a la respuesta refleja del sistema respiratorio durante esta actividad, manifestada como la presencia de tos en algunos pacientes a los que se les realiza destete del ventilador mecánico (Brewster et al. 2020). Realizar la extubación requiere la proximidad de los trabajadores de salud con los pacientes, los cuales, incluyendo los casos de pacientes con COVID-19, suelen seguir siendo infecciosos al momento de la extubación (Brewster et al. 2020, Zhou et al. 2020, Ng et al. 2020), por lo que realizar esta actividad incrementaría la probabilidad de transmisión de esta infección viral. Ante ello, diversos grupos relacionados a la anestesiología señalan como útil el empleo de medicación que reduzca la generación de tos durante la extubación, que, junto a otras medidas de protección, disminuiría la probabilidad de transmisión de la infección por SARS-CoV-2 (Brown et al. 2020, Cook et al. 2020, D'Silva et al. 2020, Tan Li et al 2020). En EsSalud, se dispone de lidocaína y fentanilo, medicamentos descritos en la literatura científica como útiles para reducir la tos en pacientes a los que se les realizará el destete de la ventilación mecánica. Sin embargo, algunos especialistas argumentan que estos agentes sedantes podrían causar depresión respiratoria, retraso en el despertar e incrementar el riesgo de delirio si son administrados por periodos largos. Adicionalmente, los especialistas argumentan que dexmedetomidina es una alternativa que ofrecería la ventaja un despertar más rápido y una menor incidencia de delirio, además de reducir la incidencia de tos durante la extubación, estos efectos facilitarían la extubación del paciente y disminuiría la transmisión del SARS-CoV-2 al equipo médico tratante en la UCI. En ese sentido, el presente documento tuvo como objetivo evaluar la eficacia y seguridad de dexmedetomidina comparado con lidocaína y fentanilo para destete de ventilación mecánica invasiva en pacientes con COVID-19. TECNOLOGÍA DE INTERÉS: Dexmedetomidina es un agonista selectivo de los receptores alfa-2 con efectos ansiolíticos, sedantes (mediados por la inhibición del locus coeruleus, el núcleo noradrenérgico predominante, situado en el tronco cerebral) y analgésicos, produciendo además un efecto simpaticolítico al disminuir la liberación de noradrenalina en las terminaciones nerviosas simpáticas. METODOLOGÍA: Se buscó la evidencia disponible al 24 de agosto del 2020 en las siguientes bases de datos bibliográficas: PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda en sitios web pertenecientes a grupos que realizan evaluaciones de tecnologías sanitarias y guías de práctica clínica, incluyendo: The Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), The National Institute for Health and Care Excellence (NICE), Institute for Quality and Efficiency in Healthcare (IQWiG), Haute Authorité de Santé (HAS), Institute for Clinical and Economic Review (ICER) y el portal BRISA (Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas). Adicionalmente, se realizó búsqueda de evidencia en sitios web de organizaciones internacionales en anestesiología o de instituciones que estén desarrollando protocolos para el manejo de pacientes con COVID-19. RESULTADOS: En la búsqueda de la evidencia no se identificaron estudios que evalúen la eficacia y seguridad de dexmedetomidina, comparado con lidocaína y fentanilo, para el destete de ventilación mecánica invasiva, en pacientes con COVID-19. Sin embargo, se identificaron: tres GPC o consensos de expertos elaborados por la Safe Airway Society, Alfred ICU y la Difficult Airway Society e instituciones colaboradoras; una RS con metaanálisis en red realizada por Tung et al., así como dos ensayos clínicos controlados, aleatorizados (ECA) que no fueron incluidos en la RS. Se debe precisar que esta RS y estos ECA no fueron realizados en la población de interés del presente reporte breve (pacientes con COVID-19); por lo que fueron incluidos como evidencia indirecta. CONCLUSIONES: En el presente documento, se evaluó la mejor evidencia científica disponible hasta la actualidad sobre eficacia y seguridad de dexmedetomidina comparado con lidocaína y fentanilo para destete de ventilación mecánica en pacientes con COVID-19. Se encontraron: tres GPC o consensos de expertos, una RS y dos ECA. La RS y los ECA incluidos aportan al reporte breve como evidencia indirecta; al no haber sido desarrollados en pacientes con COVID-19. Las guías de la Safe Airway Society (SAS), Alfred ICU y de la Difficult Airway Society (DAS) e instituciones colaboradoras que fueron elaboradas para dar recomendaciones para el proceso de extubación en pacientes con COVID-19, hacen mención a dexmedetomidina (SAS, Alfred ICU), opioides como el fentanilo (SAS y DAS) y la lidocaína (SAS, DAS) para reducir la tos durante el proceso de extubación, aunque precisan la ausencia de evidencia sobre el uso de este medicamentos en pacientes con COVID-19, señalando que se debe evaluar el balance riesgo-beneficio para el uso de los mismos. En general, las recomendaciones descritas en estos documentos proceden de consensos por opinión de expertos, y no establecen una preferencia de un medicamento sobre los otros. En cuanto a los resultados de la RS con MA en red de Tung et al., y los ECA de Kothari et al., y Hu et al., no han podido encontrar evidencia que apoye la hipótesis que el efecto de la dexmedetomidina sea superior al de lidocaína y fentanilo sobre el manejo de la tos (esto es, no se encontraron diferencias entre estos). Estos resultados deben ser interpretados con cautela debido a que la población de estudio de los mismos no son pacientes COVID-19. No obstante, la información que proporcionan puede ayudar a tener una idea del efecto que se podría esperar con el uso de cada uno de los medicamentos mencionados, tanto en eficacia como en seguridad. Al respecto, frente a una ausencia de diferencia entre dexmedetomidina en comparación con lidocaína y fentanilo, se tiene evidencia que la primera tiene un mayor riesgo de bradicardia que los dos últimos. Esto se condice con la literatura previa acerca de dicho medicamento (dexmedetomidina), donde además se describe que los adultos mayores y personas con comorbilidades presentan una mayor proporción de eventos de bradicardia atribuibles al uso de dexmedetomidina lo que, siendo que estos grupos poblacionales son los más afectados por COVID-19, sería esperable una mayor presencia de bradicardia como evento adverso en pacientes con COVID-19 que reciben dexmedetomidina, lo que llama a la precaución cuando se considera el uso de esta tecnología en estos pacientes. De este modo, la mejor evidencia disponible a la fecha (24 de agosto del 2020), procedente de tres GPC o consensos de expertos, una RS con metaanálisis en red y dos ECA, apunta a que el balance de riesgo-beneficio del empleo de dexmedetomidina comparado con el uso de lidocaína o fentanilo, en la reducción de la tos durante el destete de ventilación mecánica en pacientes con COVID-19 es de alta incertidumbre, especialmente por el hecho que la dexmedetomidina está asociada a un mayor riesgo de reacciones adversas frente a los otros dos medicamentos, especialmente en lo referente a bradicardia. Por ello, con este cuerpo de evidencia, el IETSI no ha encontrado sustento técnico que pueda apoyar una recomendación a favor del uso de dexmedetomidina por sobre el de lidocaína o fentanilo en pacientes COVID-19 para reducir la tos al momento de la extubación.