A Prospective Randomized Trial of Surgeon-Administered Intraoperative Transversus Abdominis Plane Block With Bupivacaine Against Liposomal Bupivacaine: The TINGLE Trial.

BACKGROUND: Transversus abdominis plane blocks are increasingly used to achieve opioid-sparing analgesia after colorectal surgery. Traditionally, bupivacaine was the long-acting analgesic of choice, but the addition of dexamethasone and/or epinephrine to bupivacaine may extend block duration. Liposomal bupivacaine has also been suggested to achieve an extended analgesia duration of 72 hours but is significantly more expensive. OBJECTIVE: The purpose of this study was to compare pain control between laparoscopic transversus abdominis plane blocks using liposomal bupivacaine versus bupivacaine with epinephrine and dexamethasone. DESIGN: This was a parallel-group, single-institution, randomized clinical trial. SETTINGS: The study was conducted at a single tertiary medical center. PATIENTS: Consecutive patients between October 2018 to October 2019, ages 18 to 90 years, undergoing minimally invasive colorectal surgery with multimodal analgesia were included. INTERVENTIONS: Patients were randomly assigned 1:1 to receive a laparoscopic transversus abdominis plane block with liposomal bupivacaine or bupivacaine with epinephrine and dexamethasone. MAIN OUTCOME MEASURES: The primary outcome was total oral morphine equivalents administered in the first 48 hours postoperatively. Secondary outcomes included pain scores, time to ambulation and solid diet, hospital length of stay, and complications. RESULTS: A total of 102 patients (50 men) with a median age of 42 years (interquartile range, 29-60 y) consented and were randomly assigned. The primary end point, total oral morphine equivalents administered in the first 48 hours, was not significantly different between the liposomal bupivacaine group (median = 69 mg) and the bupivacaine with epinephrine and dexamethasone group (median = 47 mg; difference in medians = 22 mg, (95% CI, -17 to 49 mg); p = 0.60). There were no significant differences in pain scores, time to ambulation, time to diet tolerance, time to bowel movement, length of stay, overall complications, or readmission rate between groups. There were no treatment-related adverse outcomes. LIMITATIONS: This study was not placebo controlled or blinded. CONCLUSIONS: This first randomized trial comparing laparoscopic transversus abdominis plane block with liposomal bupivacaine or bupivacaine with epinephrine and dexamethasone showed that a liposomal bupivacaine block does not provide superior or extended analgesia in the era of standardized multimodal analgesia protocols.See Video Abstract at http://links.lww.com/DCR/B533. ESTUDIO PROSPECTIVO Y RANDOMIZADO DE BLOQUEO DEL PLANO MUSCULAR TRANSVERSO DEL ABDOMEN REALIZADO POR EL CIRUJANO CON BUPIVACANA VERSUS BUPIVACANA LIPOSOMAL ESTUDIO TINGLE: ANTECEDENTES:El bloqueo anestésico del plano muscular transverso del abdomen se utiliza cada vez más para lograr una analgesia con menos consumo de opioides después de cirugía colorrectal. Tradicionalmente, la Bupivacaína era el analgésico de acción prolongada de elección, pero al agregarse Dexametasona y/o Adrenalina a la Bupivacaína se puede prolongar la duración del bloqueo. También se ha propuesto que la Bupivacaína liposomal logra una duración prolongada de la analgesia de 72 horas, pero es significativamente más cara.OBJETIVO:Comparar el control del dolor entre bloqueo laparoscópico del plano de los transversos del abdomen usando Bupivacaína liposomal versus Bupivacaína con Adrenalina y Dexametasona.DISEÑO:Estudio clínico prospectivo y randomizado de una sola institución en grupos paralelos.AJUSTE:Centro médico terciario único.PACIENTES:Todos aquellos pacientes entre 18 y 90 años sometidos a cirugía colorrectal mínimamente invasiva con analgesia multimodal, entre octubre de 2018 a octubre de 2019 incluidos de manera consecutiva.INTERVENCIONES:Los pacientes fueron seleccionados aleatoriamente 1:1 para recibir un bloqueo laparoscópico del plano de los transversos del abdomen con Bupivacaína liposomal o Bupivacaína con Adrenalina y Dexametasona.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el total de equivalentes de morfina oral administradas en las primeras 48 horas después de la operación. Los resultados secundarios incluyeron puntuaciones de dolor, inicio de dieta sólida, tiempo de inicio a la deambulación, la estadía hospitalaria y las complicaciones.RESULTADOS:Un total de 102 pacientes (50 hombres) con una mediana de edad de 42 años (IQR 29-60) fueron incluidos aleatoriamente. El criterio de valoración principal, equivalentes de morfina oral total administrada en las primeras 48 horas, no fue significativamente diferente entre el grupo de Bupivacaína liposomal (mediana = 69 mg) y el grupo de Bupivacaína con Adrenalina y Dexametasona (mediana = 47 mg; diferencia en medianas = 22 mg, IC del 95% [-17] - 49 mg, p = 0,60). No hubo diferencias significativas en las puntuaciones de dolor, tiempo de inicio a la deambulación, el tiempo de tolerancia a la dieta sólida, el tiempo hasta el primer evacuado intestinal, la duración de la estadía hospitalaria, las complicaciones generales o la tasa de readmisión entre los grupos. No hubo resultados adversos relacionados con el tratamiento.LIMITACIONES:Este estudio no fue controlado con placebo ni de manera cegada.CONCLUSIONES:Este primer estudio prospectivo y randomizado que comparó el bloqueo del plano de los músculos transversos del abdomen por vía laparoscópica, utilizando Bupivacaína liposomal o Bupivacaína con Adrenalina y Dexametasona, demostró que el bloqueo de Bupivacaína liposomal no proporciona ni mejor analgesia ni un efecto mas prolongado.Consulte Video Resumen en http://links.lww.com/DCR/B533.

Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia.

BACKGROUND: Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food and Drug Administration for treatment of cytokine storm associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use of tocilizumab in patients with SARS-CoV-2 pneumonia. METHODS: We report on a single-center study of tocilizumab in hospitalized patients with SARS-CoV-2 pneumonia. All patients had confirmed SARS-CoV-2 pneumonia and oxygen saturations <90% on oxygen support with most intubated. We examined clinical and laboratory parameters including oxygen and vasopressor requirements, cytokine profiles, and C-reactive protein (CRP) levels pre- and post-tocilizumab treatment. RESULTS: Twenty-seven SARS-CoV-2 pneumonia patients received one 400 mg dose of tocilizumab. Interleukin (IL)-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, 4 patients did not show rapid CRP declines, of whom 3 had poorer outcomes. Oxygen and vasopressor requirements diminished over the first week post-tocilizumab. Twenty-two patients required mechanical ventilation; at last follow-up, 16 were extubated. Adverse events and serious adverse events were minimal, but 2 deaths (7.4%) occurred that were felt unrelated to tocilizumab. CONCLUSIONS: Compared to published reports on the morbidity and mortality associated with SARS-CoV-2, tocilizumab appears to offer benefits in reducing inflammation, oxygen requirements, vasopressor support, and mortality. The rationale for tocilizumab treatment is supported by detection of IL-6 in pathogenic levels in all patients. Additional doses of tocilizumab may be needed for those showing slow declines in CRP. Proof of efficacy awaits randomized, placebo-controlled clinical trials.

Adverse Effects Associated with Patient-Controlled Analgesia with Ketamine Combined with Opioids and Ketamine Infusion with PCA Bolus in Postoperative Spine Patients: A Retrospective Review.

Objective: There has been increasing use of ketamine at subanesthetic doses as an adjunct to opioids in perioperative pain management. There are several known adverse drug effects (ADEs) associated with ketamine. However, the incidence of ADEs with ketamine infusions with patient-controlled analgesia (PCA) boluses compared with combined opioid and ketamine PCAs is not well described. The objectives of this study were to compare the incidence and type of ADEs in postoperative spine surgery patients on ketamine infusions with as-needed PCA boluses to patients on combined opioid and ketamine PCAs. Methods: The medical records of patients who underwent spine surgery between March 2016 and March 2020 who were postoperatively treated with a ketamine infusion and as-needed PCA boluses and parenteral opioids or treated with a combined opioid and ketamine PCA were reviewed. Perioperative information including patient characteristics and preoperative morphine equivalent daily dose (MEDD) were collected. Patient charts were reviewed for ADEs including psychological and neurological side effects, nausea, and new-onset tachycardia. Results: A total of 315 patients met the inclusion criteria and were included in the final analysis. Of these patients, 121 experienced at least one ADE (38%). Sixteen of the 68 ketamine infusion with PCA bolus patients (24%), 77 of the 203 hydromorphone and ketamine patients (38%), and 28 of the 44 morphine and ketamine patients (64%) experienced an ADE [p<0.01]. In patients with preoperative MEDD ≤ 90, nausea was the only ADE that differed significantly among the three groups. Conclusion: This retrospective analysis suggests that postoperative spine patients treated with a ketamine infusion with as-needed PCA boluses and parenteral opioids were associated with fewer ADEs when compared to an intravenous combined opioid and ketamine PCA. In patients with preoperative MEDD ≤ 90, nausea with and without emesis was the only ADE that showed statistically significant difference amongst the three groups.