Liposomal Bupivacaine Transversus Abdominis Plane Block Versus Epidural Analgesia in a Colon and Rectal Surgery Enhanced Recovery Pathway: A Randomized Clinical Trial.

BACKGROUND: Multimodal pain management is an integral part of enhanced recovery pathways. The most effective pain management strategies have not been determined. OBJECTIVE: The purpose of this study was to compare liposomal bupivacaine transversus abdominis plane block with epidural analgesia in patients undergoing colorectal surgery. DESIGN: This is a single-institution, open-label randomized (1:1) trial. SETTING: This study compared liposomal bupivacaine transversus abdominis plane block with epidural analgesia in patients undergoing elective open and minimally invasive colorectal surgery in an enhanced recovery pathway. PATIENTS: Two hundred were enrolled. Following randomization, allocation, and follow-up, there were 92 patients with transversus abdominis plane block and 87 patients with epidural analgesia available for analysis. INTERVENTIONS: The interventions comprised liposomal bupivacaine transversus abdominis plane block versus epidural analgesia. MAIN OUTCOME MEASURES: The primary outcomes measured were numeric pain scores and the overall benefit of analgesia scores. RESULTS: There were no significant differences in the Numeric Pain Scale and Overall Benefit of Analgesia Score between groups. Time trend analysis revealed that patients with transversus abdominis plane block had higher numeric pain scores on the day of surgery, but that the relationship was reversed later in the postoperative period. Opioid use was significantly less in the transversus abdominis plane block group (206.84 mg vs 98.29 mg, p < 0.001). There were no significant differences in time to GI recovery, hospital length of stay, and postoperative complications. Cost was considerably more for the epidural analgesia group. LIMITATIONS: This study was conducted at a single institution. CONCLUSIONS: This randomized trial shows that perioperative pain management with liposomal bupivacaine transversus abdominis plane block is as effective as epidural analgesia and is associated with less opioid use and less cost. These data and the more favorable risk profile suggest that liposomal bupivacaine transversus abdominis plane block is a viable multimodal perioperative pain management option for this patient population in an established enhanced recovery pathway. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov (NCT02591407). See Video Abstract at http://links.lww.com/DCR/A737.

Cardiocirculatory intraoperative assessment during single-shot caudal anaesthesia in children: comparison between levobupivacaine and ropivacaine.

BACKGROUND: Caudal block with levobupivacaine or ropivacaine is the most commonly used regional anaesthesia in children. METHODS: The aim of study was to compare the cardiocirculatory profile induced in two matched groups of young patients, submitted to caudal anaesthesia with levobupivacaine or ropivacaine for an elective subumbilical surgery. Sixty children were enrolled: thirty received levopubivacaine 0.25% and thirty ropivacaine 0.2%. Intraoperative heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) were monitored at following times: Ta0 (after anaesthesia induction), Tal (after caudal anaesthesia), Ta2 (five minutes later), Ta3 (ten minutes later), Ts1 (at surgical incision), Ts2, Ts3, Ts4, Ts5 (every 10 minutes during surgery), Taw (at the awakening). RESULTS: In both groups the cardiocirculatory trend remained within normal ranges at all times considered, demonstrating the safety of the method with both drugs. Both groups showed a similar trend at the different monitoring times: low decrease in HR, SBP and DBP after caudal block, slight increase in parameters after skin incision, slight decrease during surgery, increase at awakening. Regarding SBP and DBP, the levobupivacaine group children generally showed higher levels compared to the ropivacaine group, especially for DBP. CONCLUSIONS: Paediatric caudal anaesthesia is an effective method with an very infrequent complication rate. Possible hypotheses for differing haemodynamic behaviour could include a stronger vasoconstriction reflex of innervated areas during caudal anaesthesia with levobupivacaine and a lower levobupivacaine induced block of the sympathetic fibers, related to different pharmacokinetic profile of low concentrations of the local anaesthetics used in paediatric epidural space.

Auditory evoked potential index does not correlate with observer assessment of alertness and sedation score during 0.5% bupivacaine spinal anesthesia with nitrous oxide sedation alone.

PURPOSE: The aim of this study was to evaluate the auditory evoked potential (AEP) index as a hypnosis monitor during nitrous oxide (N(2)O) sedation added to spinal analgesia. METHODS: Forty-five patients scheduled to undergo surgery under spinal anesthesia were recruited after giving informed consent. Adequate anesthesia levels were confirmed, and a disposable AEP index sensor (aepEX, Medical Device Management) was placed. A tight facemask was fitted, and a fresh gas flow of 100% oxygen 10 L/min was provided. AEP index monitoring was then initiated, and measurements and observer assessment of alertness/sedation (OAA/S) scores were recorded manually. N(2)O was administered in stepwise increases in the end-tidal concentration of 33%, 50%, and 67%. Paired AEP index and OAA/S scores were obtained immediately before each change in N(2)O concentration. RESULTS: Sixteen patients were excluded from final analysis because of nausea, vomiting, or abnormal excitatory behaviors. The increases in N(2)O concentration induced significant decreases in OAA/S scores and no substantial AEP index changes. Although OAA/S scores of 1 and 2 were observed in only two and five patients, respectively, a reduction in the OAA/S score from 5 to 1 was associated with a significant decrease in AEP index to the level indicative of moderate sedation. CONCLUSION: The AEP index might not be a suitable indicator of light hypnosis as defined by an OAA/S score of ≥3 during sedation with N(2)O alone.

The beneficial effects of preperitoneal catheter analgesia following colon and rectal resections: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: Preperitoneal catheter analgesia following abdominal surgery has attracted interest in the last decade. We conducted this study to evaluate the benefits of preperitoneal catheter analgesia in managing pain after abdominal colon and rectal resections. METHODS: A total of 50 patients undergoing colon and rectal resections for benign and malignant diseases received analgesic medicines via an epidural catheter placed just prior to surgery and a preperitoneal catheter placed at the end of the surgical procedure. Patients were instructed to use the epidural patient-controlled analgesia (PCA) device freely and were randomized into two groups after obtaining the approval of the Institutional Review Board: Group A received 10 ml of levobupivacaine twice a day postoperatively via preperitoneal catheter and group B received only 10 ml of saline. Demographics, surgical characteristics, pain scores recorded four days following surgery, analgesic volume used from the epidural PCA, clinical outcomes (length of stay, time to first bowel movement, time to first passage of gas or stool, time to first oral intake) and respiratory function test results (preoperative vs. postoperative) were compared. RESULTS: There were no significant differences in demographics or surgical characteristics between both groups. Pain scores were similar. Clinical outcomes and respiratory functions were comparable. The use of analgesic volume via epidural catheter was significantly lower in group A than in group B (P = 0.032). CONCLUSIONS: Preperitoneal catheter analgesia significantly decreased the need for epidural drug consumption and proved to be a beneficial adjunct for postoperative pain management of patients who underwent colon and rectal resections.

In vitro assessment of human chondrocyte viability after treatment with local anaesthetic, magnesium sulphate or normal saline.

PURPOSE: Local anaesthetic agents are often used as an intra-articular analgesic following arthroscopic procedures. However, there is increasing evidence of a potential toxic effect to chondrocytes within the articular cartilage. The aim of this study was to compare the effect on human chondrocyte viability of treatment with bupivacaine, levobupivacaine and ropivacaine. The second aim was to compare the effect on chondrocyte viability of the local anaesthetics with magnesium, a potential alternative analgesic agent. METHODS: Chondrocytes were exposed to one of the local anaesthetic agents (levobupivacaine 0.13, 0.25, 0.5%; bupivacaine 0.13, 0.25, 0.5%; ropivacaine 0.19, 0.38, 0.75%), normal saline or 10% magnesium sulphate for 15 min. Cells exposed to cell culture media served as controls. Twenty-four hours after exposure, cell viability was assessed using the CellTiter 96® AQueous One Solution Cell Proliferation Assay. RESULTS: There was no significant difference in chondrocyte viability after treatment with either normal saline or magnesium sulphate. With the exception of 0.13% levobupivacine, all local anaesthetic treatment showed significantly greater toxic effects than either normal saline or magnesium sulphate. Statistically significant dose-dependent responses of decreasing cell viability were found with increasing local anaesthetic concentration. CONCLUSIONS: A dose-dependent reduction in chondrocyte viability after treatment with common local anaesthetic agents was confirmed. Local anaesthetic agents had a greater deleterious effect on chondrocytes than did 10% magnesium sulphate. These findings suggest the need for continuing caution with the use of intra-articular local anaesthetic. Magnesium sulphate is a potential alternative intra-articular analgesic agent.

Epidural analgesia after scoliosis surgery: electrophysiologic and clinical assessment of the effects of bupivacaine 0.125% plus morphine versus ropivacaine 0.2% plus morphine.

STUDY OBJECTIVE: To study the electrophysiologic and clinical effects of epidural morphine combined with either bupivacaine 0.125% or ropivacaine 0.2%. DESIGN: Comparative, randomized, double-blind study. SETTINGS: Intensive care unit and hospital ward of a university hospital. PATIENTS: 18 adult ASA physical status I and II patients with degenerative or idiopathic scoliosis, undergoing posterior spinal fusion with instrumentation. INTERVENTIONS: Patients received epidural administration of 10-mL bolus of either bupivacaine or ropivacaine followed by a 6-mL/h infusion for 48 hours of unlabeled local anesthetic. In all patients, epidural morphine 5 mg was added daily. MEASUREMENTS: Assessment was focused mainly on somatosensory cortical evoked potentials, soleus H-reflex, and F waves. These electrophysiologic data were recorded before and after epidural medications. Second, respiratory rate, Paco(2), visual analog score (VAS), and side effects such as postoperative nausea and vomiting (PONV), gastrointestinal (GI) transit delay, and urinary retention were noted. MAIN RESULTS: Bupivacaine 0.125% + morphine was given to 9 patients, and ropivacaine 0.2% + morphine was given to 9 other patients. H-reflex, F waves, and somatosensory cortical evoked potential recording remained unchanged across the time of assessment. Respiratory rate and Paco(2) values were normal. VASs were indifferently low at rest, but they were lower with bupivacaine than with ropivacaine on mobilization. The frequency of PONV was indifferently high. No altered GI transit or urinary retention was noted. CONCLUSION: After epidural administration during the study conditions, bupivacaine 0.125% and ropivacaine 0.2% combined with morphine allow for neurologic examination.

Bispectral index does not correlate with observer assessment of alertness and sedation scores during 0.5% bupivacaine epidural anesthesia with nitrous oxide sedation.

The bispectral index (BIS) has been used as a measure of the degree of sedation and level of hypnosis for IV hypnotics and sedatives, potent volatile anesthetics. We evaluated the effect of increasing concentrations of nitrous oxide (N2O) on BIS and compared it with the Observer's Assessment of Alertness and Sedation (OAA/S) scale in patients undergoing regional anesthesia. We studied 48 unpremedicated, ASA physical status I-II adult patients scheduled for lower extremity surgery under lumbar epidural anesthesia. N2O was given in oxygen to achieve measured end-tidal concentrations of 33%, 50%, and 67% N2O by a tight-fitting facemask, and each N2O concentration was maintained for 20 min. Paired measurements of BIS and OAA/S scores were obtained just before each increase in N2O concentration. Forty of the 48 subjects completed the study. Increasing N(2)O concentrations produced no changes in BIS despite a significant decrease in OAA/S scores at 50% and 67% N2O concentrations. The prediction probability for BIS and OAA/S calculated by Somers' d(x.y) were 0.60 and 0.84, respectively. Anesthesiologists should be aware that the BIS monitor may not be sensitive enough to provide an adequate measure of the depth of sedation and hypnosis when using N2O alone for sedation. It may be better to monitor sedation clinically (e.g., with the OAA/S scale) to determine the dose requirement and the adequacy of depth of sedation and hypnosis.

Comparative assessment of conduction anesthesia produced by procaine, marcaine, richlocaine, and RU-353.

Conduction anesthesia of the vagus nerve produced by procaine (0.5%), marcaine (0.25%), richlocaine (0.5%), and imidazobenzoimidazole derivative RU-353 (0.25%) was compared in acute experiments on cats. RU-353 produced the most long-term local anesthesia (assessed by inhibition of cardiochronotropic effect of vagus nerve).

Cardiac and CNS toxicity of levobupivacaine: strengths of evidence for advantage over bupivacaine.

Bupivacaine is currently the most widely used long-acting local anaesthetic. Its uses include surgery and obstetrics; however, it has been associated with potentially fatal cardiotoxicity, particularly when given intravascularly by accident. Levobupivacaine, a single enantiomer of bupivacaine, has recently been introduced as a new long-acting local anaesthetic with a potentially reduced toxicity compared with bupivacaine. Numerous preclinical and clinical studies have compared levobupivacaine with bupivacaine and in most but not all studies there is evidence that levobupivacaine is less toxic. Advantages for levobupivacaine are seen on cardiac sodium and potassium channels, on isolated animal hearts and in whole animals, anaesthetised or awake. In particular the intravascular dose of levobupivacaine required to cause lethality in animals is consistently higher compared with bupivacaine. In awake sheep, for example, almost 78% more levobupivacaine was required to cause death. In contrast, in anaesthetised dogs no differences were seen in the incidence of spontaneous or electrical stimulation- induced ventricular tachycardia and fibrillations among animals exposed to levobupivacaine or bupivacaine. The reversibility of levobupivacaine-induced cardiotoxicity has also been assessed. Some data point to an advantage of levobupivacaine over bupivacaine but this potential advantage was not confirmed in a recent study in anaesthetised dogs. Three clinical studies have been conducted using surrogate markers of both cardiac and CNS toxicity. In these studies levobupivacaine or bupivacaine were given by intravascular injection to healthy volunteers. Levobupivacaine was found to cause smaller changes in indices of cardiac contractility and the QTc interval of the electrocardiogram and also to have less depressant effect on the electroencephalogram. Assuming that levobupivacaine has the same local anaesthetic potency as bupivacaine, then, all things being equal, it is difficult to argue that levobupivacaine should not displace bupivacaine as the long-acting local anaesthetic of choice. It would appear, however, that levobupivacaine has not yet significantly displaced bupivacaine from the markets in which it is sold. This may be due to a lack of perceived safety benefit and/or consideration of the additional costs that are associated with switching to levobupivacaine, which is approximately 57% more expensive than bupivacaine. If the price of levobupivacaine were closer to bupivacaine then the argument to switch to levobupivacaine would undoubtedly be much stronger. With the continued clinical use of levobupivacaine the database available to make comparisons will increase and this may allow cost-benefit arguments to be made more forcefully for levobupivacaine in the future.

Does prior administration of enoxaparin influence the effects of levobupivacaine on blood clotting? Assessment using the Thrombelastograph.

The low molecular weight heparin, enoxaparin (by inhibition of factors Xa and IIa) and amide local anaesthetics (by altering platelet function) exert anti-clotting effects. Although these agents are often used in combination during the perioperative period, their potential interactive effect on clotting has not been defined. Blood from 10 ASA I-II patients who received enoxaparin 0.5 mg kg(-1) s.c. was studied using a Thrombelastograph (TEG) either alone or in combination with levobupivacaine (2.5 mg ml(-1) or 2.5 microg ml(-1)) or saline (50% dilution). In blood from patients who had received enoxaparin 0.5 mg kg(-1) s.c. 12 h previously, levobupivacaine 2.5 mg ml(-1) (but not 2.5 microg ml(-1)) produced significant changes in TEG clotting parameters (mean (SD) 15.7 (4.8) mm, 29.6 (25.6) mm, 34.4 (14.6) mm, 34.3 (12.2) degrees compared with control values of 6.1 (1.3) mm, 2.5 (0.5) mm, 63.5 (6.4) mm and 74.1 (2.9) degrees for r, K, MA, and alpha angle respectively).

Valoración cinética y dinámica de la Bupivacaina al 0.5 por ciento con adrenalina al 1: 200.000 en anestesia infiltrativa / Kinetic and dynamic valuation of bupivacaine at 0.5 with adrenaline at 1: 200.000 in infiltration anesthetic

En la práctica odontológica se plantea la necesidad de utilizar anestésicos locales cuyo comportamiento farmacológico permita desarrollar intervenciones de duración prolongada. Propósito: evaluar el período de latencia, profundidad anestésica y duración del efecto en la Bupivacaína al 0.5 por ciento con adrenalina al 1:200.000 en anestesia dental infiltrativa. Método: mediante evaluación subjetiva y la utilización de un vitalómetro digital se valoraron los parámetros cinéticos y la farmacodinamia de la Bupivacaína, después de su administración infiltrativa de 4.5 mcg de adrenalina en un volumen de 0.9 ml. Resultados: el período de latencia se ubicó entre 45-120 segundos. La duración del efecto anestésico se situó entre 120-300 minutos y la profundidad anestésica fluctuó entre 120 y 270 minutos. Conclusiones: la Bupivacaína al 0.5 por ciento con adrenalina al 1:200.000 ofrece una alternativa viable para procedimientos odontológicos que requieran de un efecto anestésico prolongado.

Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine. Assessment with closed spinal window technique.

BACKGROUND: Ropivacaine produces a vasoconstriction of cutaneous vessels in contrast to vasodilation produced by bupivacaine. To evaluate direct spinal microvascular actions of these local anesthetics, the authors investigated the concentration-related effects of ropivacaine and bupivacaine on spinal pial vascular diameters using the spinal window technique. METHODS: Anesthetized dogs (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were prepared for measurement of spinal pial vessel diameters by intravital microscopy in a spinal window preparation. The authors administered six concentrations of each drug (10(-8)-10(-3) M) under the window and directly measured the spinal pial arteriolar and venular diameters at sequential times. Physiologic data including mean arterial blood pressure (MAP) and heart rate (HR) were determined before and after topical application of each concentration of the drugs. In additional experiments (n = 18), the action of topical ropivacaine and bupivacaine solution on spinal vessels was evaluated in the presence of yohimbine, prazosin, and propranolol. RESULTS: Ropivacaine significantly constricted whereas bupivacaine dilated pial arterioles and venules, both in a concentration-dependent manner. Microvascular alteration was not blocked with any of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each of which per se did not affect pial vessel diameters. Topical application of ropivacaine or bupivacaine did not induce any change in MAP or HR. CONCLUSIONS: The present results indicate that ropivacaine constricts and bupivacaine dilates the pial vessels of the spinal cord in a concentration-dependent fashion, and the mechanisms involved in such actions do not seem to be mediated via alpha- or beta-adrenoceptor of spinal vasculature.

Control del dolor postoperatorio con bupivacaina intrapleural sin cateter / Pain control post-operatorio fron intrapleural Bupivacain non-cateter

Se operaron 25 pacientes con patología torácica, sin dolor torácico preoperatorio inmediato y con estados físicos grados II ó III de las normas ASA. Todos tenían estudios funcionales respiratorios y gasometría arterial preoperatorios. Se los instruyó para valorar la intensidad del dolor postoperatorio mediante una escala analógica y fueron informados del uso intraoperatorio de anestésicos con efecto postoperatorio. Este anestésico se instiló sobre la cadena simpática en solución de bupivacaína-adrenalina al 0,5%. Todos recibieron el mismo analgésico en el postoperatorio. Hubo un grupo control que no recibió la solución anestésica. Existieron diferencias significativas entre ambos grupos, con disminución subjetiva del dolor, que se mantuvo durante todo el postoperatorio inmediato. Menos dosis de analgésicos necesitaron los enfermos que habían recibido la solución de bupivacaína. No hubo complicaciones por este procedimiento.

Caudal analgesia for pediatric day case surgery: assessment of motor function prior to discharge.

The benefits of caudal analgesia are well recognized in the prevention of postoperative pain following pediatric surgery. The possibility of motor weakness may deter anesthetists from using this technique. This study investigates motor function prior to discharge in boys who, as day case patients, received caudal analgesia for pain relief following circumcision. Motor function was assessed using a simple and clinically relevant scale. Three different dosage regimens of bupivacaine were compared. No important motor weakness was demonstrated, and there was no difference with respect to motor block in the three groups. Caudal analgesia may be recommended as a suitable technique for day case patients.