Super-refractory status epilepticus, rhabdomyolysis, central hyperthermia and cardiomyopathy attributable to spinal anesthesia: a case report and review of literature.

BACKGROUND: There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine was administered to all six of them and to our case. Pathophysiology ensuing such cases remains unclear. CASE PRESENTATION: A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy. Her current pregnancy was uneventful. Her American Society of Anesthesiologists (ASA) grade was 2. She underwent spinal anesthesia and adequate anesthesia was achieved. After 5-7 min she developed a progressive myoclonus. After delivery of a healthy baby, she developed generalized tonic clonic seizures that continued despite the induction of general anesthesia. She had rhabdomyolysis, one brief cardiac arrest and resuscitation, followed by stress cardiomyopathy and central hyperthermia. She died on day four. There were no significant macroscopic or histopathological changes in her brain that explain her super refractory status epilepticus. Heavy bupivacaine samples of the same batch used for this patient were analyzed by two specialized laboratories. National Medicines Quality Assurance Laboratory of Sri Lanka reported that samples failed to confirm United States Pharmacopeia (USP) dextrose specifications and passed other tests. Subsequently, Therapeutic Goods Administration of Australia reported that the drug passed all standard USP quality tests applied to it. Nonetheless, they have detected an unidentified impurity in the medicine. CONCLUSIONS: After reviewing relevant literature, we believe that direct neurotoxicity by bupivacaine is the most probable cause of super-refractory status epilepticus. Super-refractory status epilepticus would have led to her other complications and death. We discuss probable patient factors that would have made her susceptible to neurotoxicity. The impurity in the drug detected by one laboratory also would have contributed to her status epilepticus. We propose several possible mechanisms that would have led to status epilepticus and her death. We discuss the factors that shall guide investigators on future such cases. We suggest ways to minimize similar future incidents. This is an idiosyncratic reaction as well.

Bupivacaine pleural effusion mimicking a hemothorax after a thoracoscopic microdiscectomy with epidural anesthesia.

PURPOSE: Post-operative pain after video-assisted thoracoscopic surgery is often treated using thoracic epidural analgesics or thoracic paravertebral analgesics. This article describes a case where a thoracic disc herniation is treated with a thoracoscopic microdiscectomy with post-operative thoracic epidural analgesics. The patient developed a bupivacaine pleural effusion which mimicked a hemothorax on computed tomography (CT). METHODS: The presence of bupivacaine in the pleural effusion was confirmed using a high performance liquid chromatography method. RESULTS: The patient underwent a re-exploration to relieve the pleural effusion. The patient showed a long-term recovery similar to what can be expected from an uncomplicated thoracoscopic microdiscectomy. CONCLUSION: A pleural effusion may occur when thoracic epidural analgesics are used in patents with a corridor between the pleural cavity and epidural space.

Opioid-Sparing Effects of the Bupivacaine Pleural Catheter in Surgical Decompression of the Thoracic Outlet.

BACKGROUND: Rib resection in thoracic outlet decompression can result in significant postoperative pain requiring high levels of opioid medications. We evaluated the impact of a bupivacaine infusing pleural catheter on postoperative pain and opioid usage in patients undergoing rib resection for thoracic outlet syndrome. We hypothesized that delivery of local anesthetic via the pleural catheter would improve postoperative pain control compared to standard multimodal analgesia, and that the use of the catheter would decrease opioid use during the index hospitalization and prescriptions for opioid pain medications at discharge. METHODS: We conducted a single-center retrospective cohort study of 26 patients who underwent rib resection for thoracic outlet decompression. Primary outcome was opioid consumption during the index hospitalization, measured in morphine milligram equivalents (MME). Secondary outcomes were MME prescribed at discharge and pain scores during the index hospitalization before and after the pleural drain and pleural catheter were removed. RESULTS: Patients in the bupivacaine infusion pleural catheter group (n = 11) had significantly lower MME usage during the index hospitalization (22.5 [1.9, 65.6] vs. 119.8 [76.5, 167.4]), and significantly lower MME prescribed at discharge (0 [0, 37.5] vs. 225 [183, 315]), compared to standard multimodal analgesia in controls (n = 15). Only 3 patients in the bupivacaine pleural catheter group were discharged with any opioid prescriptions (27%), compared to 14 patients in the control group (93%). There was no difference in postoperative pain scores between groups before or after removal of the pleural drain, which was placed in all cases (P = 0.31 and P = 0.76, respectively). CONCLUSIONS: Intraoperative placement of a bupivacaine infusion pleural catheter significantly reduced opioid use during the index hospitalization and opioid prescribing at discharge. Anesthetic infusion pleural catheters should be the treatment modality of choice for postoperative pain management in patients undergoing thoracic outlet decompression.

TRANSCARUNCULAR DOUBLE INJECTION TECHNIQUE FOR PERIBULBAR ANESTHESIA IN VITREORETINAL SURGERY.

PURPOSE: Local anesthesia is commonly adopted in vitreoretinal surgery to reach painless and akinesia surgical condition. Currently, peribulbar anesthesia (PBA) and subtenon injection (STN) are the most widely used methods. We propose a transcaruncular double injection peribulbar technique (TRS) and aim to compare it with both standard PBA and STN injections. METHODS: A total of 105 patients underwent TRS, PBA, or STN. A numerical rating scale was used to assess preoperative, postoperative, and intraoperative pain. Best akinesia score and onset and duration of akinesia were evaluated by two independent graders. The need for supplementary injection was also registered. RESULTS: TRS group was characterized by a lower intraoperative numerical rating scale variation and absolute numerical rating scale score both at the beginning of surgery ( P 0.046), after 30 minutes ( P 0.032), and at the end of surgery ( P 0.002) compared with the other groups. The TRS group also showed better akinesia score ( P 0.004), fastest onset ( P 0.002), and longer duration ( P 0.042) compared with both PBA and STN. No injection-related complications were reported in the three groups. CONCLUSION: The newly proposed transcaruncular PBA provided superior pain control and akinesia level with no additional adverse events.

Anesthesia characteristic of an algorithm of bupivacaine dose based on height in caesarean section under spinal anesthesia: a retrospective cohort study.

BACKGROUND: An algorithm of bupivacaine dose based on height is applied to reduce maternal hypotension in caesarean section under spinal anesthesia. This study is designed to further verify whether the algorithm of bupivacaine dose based on height is suitable. METHODS: The parturients were grouped according to height. The comparison of anesthesia characteristic among subgroups was carried out. The univariate and multivariate binary logistic regressions were executed to reanalyze the interference factor for the anesthesia characteristic. RESULTS: When the dose of bupivacaine was adjusted by using the height based dosing algorithm, except for weight (P < 0.05), other general data did not present statistical changes with height (P > 0.05); the incidences of complications, characteristics of sensory or motor block, quality of anesthesia and neonatal outcome were of no statistical difference among parturients with different heights (P > 0.05); the height, weight and body mass index were not related with maternal hypotension (P > 0.05). When the dose of bupivacaine is constant, except for weight and body mass index (P > 0.05), the height was the independent risk factor for maternal hypotension (P < 0.05). CONCLUSIONS: Except for weight and body mass index, the height has an influence on the bupivacaine dose. It is reasonable that the bupivacaine dose is adjusted by using this dosing algorithm based on height. TRIAL REGISTRATION: This study was registered at http://clinicaltrials.gov (13/04/2018, NCT03497364).

Postoperative injectable opioid use and incidence of surgical site complications after use of liposomal bupivacaine in canine gastrointestinal foreign body surgery.

OBJECTIVE: To compare postoperative analgesic use and postoperative complications between dogs that received liposomal bupivacaine (LB) during surgical gastrointestinal foreign body (GIFB) removal and those that did not. STUDY DESIGN: Retrospective study. ANIMALS: Two hundred five dogs. METHODS: Medical records for all dogs with GIFB removal at the Purdue University Veterinary Hospital between May 2017 and August 2021 were searched. Incomplete records and dogs with less than 2 weeks' veterinary follow up were excluded. Data collected included: patient information, time until surgery, intraoperative findings, surgical data (including perforation at time of surgery, linear vs. solid, enterotomy vs. enterectomy), use of LB (including time and manner of administration), time to extubation after surgery, in-hospital postoperative analgesic use and duration, and postoperative complications. Fentanyl was noted as used/not used, quantified as mean hourly rate over 12 h intervals. All analyses were performed using commercial statistical software with p < .05 as the significance level. RESULTS: Dogs that received LB were heavier (n = 65, median 28.5 kg) than those that did not (n = 140, median 24.4 kg) (p = .005). Postoperative fentanyl use (p < .05 between 13 and 72 h) and hourly rates (p < .05 between 13 and 48 h) were less, and postoperative time in the intensive care unit (ICU) (p < .001) and hospital were shorter (p < .001) in dogs receiving LB. Postoperative wound complications were seen in 7/65 dogs (10.8%, 95% CI = 4.4-21.0%) with LB and 4/140 (2.9%, 95% CI = 0.8-7.2%) without LB (p = .039). CONCLUSION: Use of LB was associated with reduced postoperative analgesic use, and shortened ICU and hospital stay but also with wound complications. CLINICAL SIGNIFICANCE: Caution should be used when using LB in (clean) contaminated surgeries.

Plasma concentrations of levobupivacaine in neonates during caudal epidural analgesia maintained over 48 hours.

BACKGROUND: Differences in neonatal pharmacokinetics are known to cause systemic accumulation of levobupivacaine with adverse effects during epidural analgesia. Therefore, it is not recommended to surpass 48 hours of administration in neonates. Free and total levobupivacaine levels are considered as predictors of toxicity. OBJECTIVE: The aim of the LEVON pilot study was to detect the accumulation of levobupivacaine during epidural analgesia exceeding 48 hours in neonates. METHODS: Ten neonates received a loading dose of levobupivacaine (1.25 mg/kg) followed by a continuous infusion (0.2 mg/kg/hour) epidurally. Free and total levobupivacaine concentrations were measured 0.5, 1, 6, 12, 36, 72 and 144 hours after the start of infusion. Cumulative doses of levobupivacaine, pain scores and clinical signs of toxicity were used for assessing efficacy and safety. RESULTS: The median concentrations of total levobupivacaine were 586.0, 563.0, 837.5, 957.0, 1930.0, 708.5 and 357.5 ng/ml. The median concentrations of free levobupivacaine were 4.0, 3.6, 5.5, 3.6, 5.5, 0.8 and 0.0 ng/ml. Three patients reached concerning concentrations of total levobupivacaine. Levels of free levobupivacaine remained low. No signs of toxicity were observed. CONCLUSION: Caudal epidural analgesia with levobupivacaine lasting longer than 48 hours appears to be safe providing that free levobupivacaine levels are below the presumed threshold for toxicity (Tab. 1, Fig. 1, Ref. 29). Text in PDF www.elis.sk Keywords: free levobupivacaine, total levobupivacaine, neonate, caudal continuous epidural analgesia, postoperative pain.

Local infiltration of HYR-PB21, a sustained-release formulation of bupivacaine, provides analgesia and reduces opioid requirement after haemorrhoidectomy: a randomised controlled trial.

BACKGROUND: HYR-PB21 is a new sustained-release formulation of bupivacaine indicated for controlling postoperative pain. The objectives of this study were to investigate the analgesic efficacy and safety profile of HYR-PB21 in patients after haemorrhoidectomy. METHODS: This was a multicentre, randomised, double-blind, positive-controlled trial. Patients were assigned randomly to receive a single dose of HYR-PB21 (150 mg or 300 mg) or bupivacaine HCl (75 mg) after surgery for prolapsing haemorrhoids. Postoperative pain was evaluated using a numeric rating scale at rest to calculate a cumulative pain score. Total rescue opioid usage and the proportion of subjects receiving rescue opioid were also assessed. RESULTS: We enrolled 72 patients with haemorrhoidectomy, and 71 patients completed the study. The average cumulative pain score through 72 h after surgery in the 300 mg HYR-PB21 group (87 scores) was lower than in the bupivacaine HCl group (166 scores) in an intention-to-treat analysis (P<0.001). There was a dose-response effect in reducing total opioid usage and the proportion of rescue opioid use between the 150 mg and 300 mg HYR-PB21 groups, with bupivacaine HCl as a reference group. The HYR-PB21 groups did not show more adverse effects than the bupivacaine HCl group. CONCLUSIONS: Local infiltration of a single dose of HYR-PB21 sustained-release bupivacaine had better efficacy in controlling postoperative pain, with similar adverse effects, compared with a single dose of bupivacaine HCl in patients after haemorrhoidectomy. CLINICAL TRIAL REGISTRATION: ChiCTR2000041318 (Chinese Clinical Trial Registry).

The Bupivacaine Story: A Tribute to George A. Albright, MD (1931-2020).

In 1979, George A. Albright, MD (1931-2020) published a controversial editorial in Anesthesiology that raised the question of bupivacaine cardiotoxicity. In it, he presented several cases of rapid cardiovascular collapse after administration of the highly lipophilic local anesthetic and called for further investigation. Although the scientific community initially resisted Dr Albright's idea, his editorial would ultimately lead to several important advancements in anesthesiology. In 1983, the US Food and Drug Administration issued a black box warning that recommended against the use of 0.75% bupivacaine in obstetric anesthesia. This warning would remain in place until 1999. In addition, Dr Albright's article led to the following changes: laboratory research that proved the cardiotoxicity of bupivacaine; the development of safer, stereoselective agents like ropivacaine; and the acceptance of lipid emulsion as a treatment for local anesthetic toxicity. In this article, C. Philip Larson, Jr, MDCM, Editor-in-Chief of Anesthesiology at the time of publication of Albright's manuscript, provides a unique perspective on the bupivacaine story.

Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats.

BACKGROUND: Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics. METHODS: Anesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg-1·min-1 normal saline, group LE received 2 ml·kg-1·min-1 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg-1·min-1 until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated. RESULTS: All three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4-20.7] versus 7.2 [5.9-8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0-29.1] versus 11.3 [10.7-13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9-11.7] versus 5.6 [4.5-7.0], p = 0.060). CONCLUSIONS: Our data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.

Comparison of equipotent doses of intrathecal hyperbaric prilocaine 2% and hyperbaric bupivacaine 0.5% for elective caesarean section: A prospective, randomised, controlled, two-centre clinical trial.

BACKGROUND: Elective caesarean section is performed mainly under spinal anaesthesia using hyperbaric bupivacaine combined with opioids. Despite rapid onset, good quality anaesthesia, bupivacaine provides a long duration of motor block and is related to maternal hypotension. Current policies appeal for implementation of enhanced recovery procedures after caesarean section. Hyperbaric prilocaine is an intermediate-acting local anaesthetic known for its efficacy in ambulatory surgery. Evidence on the clinical relevance of intrathecal prilocaine use for caesarean section is currently lacking. OBJECTIVES: We aimed to investigate whether hyperbaric prilocaine would offer a shorter motor block and recovery than bupivacaine, when comparing equipotent doses. We also assessed the characteristics of sensory block, maternal haemodynamics and side effects for both mother and newborn. DESIGN: Prospective, randomised, double-blind, controlled, two-centre, clinical trial. SETTING: One university teaching hospital and one general teaching hospital in Brussels, Belgium. PATIENTS: American Society of Anesthesiologists' physical status 2 parturients (n = 40) undergoing caesarean section under spinal anaesthesia. INTERVENTIONS: Patients were randomly assigned to receive spinal anaesthesia using hyperbaric prilocaine 50 mg or hyperbaric bupivacaine 10 mg, both given with sufentanil 2.5 µg and morphine 100 µg. An epidural catheter was introduced as a backup in case of failure. MAIN OUTCOMES: The primary outcome was the motor block regression (modified Bromage scale 1 to 6). Secondary outcomes included sensory block characteristics, first unassisted ambulation, maternal side effects, newborns' parameters and overall satisfaction. RESULTS: Median [IQR] motor block was significantly shorter in the hyperbaric prilocaine group (110 [104 to 150] min versus 175 [135 to 189] min, P = 0.001). First unassisted ambulation was achieved earlier after prilocaine (204.5 [177 to 246.5] min versus 314 [209.25 to 400] min, P = 0.007), and the incidence of maternal hypotension was significantly higher with bupivacaine (P = 0.033). No supplementary epidural analgesia was needed. CONCLUSION: Prilocaine provides shorter motor block, faster recovery and better haemodynamic stability than bupivacaine while offering equivalent surgical anaesthesia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02973048, EudraCT: 2016-003010-26.

Incidence and severity of short-term incisional complications after intraoperative local infiltration of liposomal bupivacaine in dogs.

OBJECTIVE: To report the incidence of short-term incisional complications in dogs receiving intraoperative local infiltration of liposomal bupivacaine. STUDY DESIGN: Retrospective study. ANIMALS: Client-owned dogs (n = 218). METHODS: Medical records were searched for dogs whose surgical site was infiltrated with liposomal bupivacaine. Records were reviewed for complications within 20 days postoperatively. Cases were categorized by: (1) surgical wound classification (clean, clean-contaminated, contaminated); (2) labeled versus off-label use in orthopedic surgery - stifle surgery to address cranial cruciate ligament (CCL) disease versus other orthopedic procedures; and (3) orthopedic versus soft-tissue surgery. RESULTS: Complications were documented in 43/218 (19.7%) records, including 27/218 (12.4%) complications that resolved spontaneously or with topical treatment. The incidence of short-term incisional complications did not differ between surgical wound classifications (P = 0.55) or between labeled versus off-label use in orthopedic surgery (P = 0.21). Complications seemed more common after soft-tissue procedures (32/123; 26.0%) than orthopedic procedures (11/95; 11.6%) (P < 0.01). CONCLUSION: Surgical wound classification or type of orthopedic procedure did not seem to influence incisional complications of infiltrated surgical sites. Complications were more common after soft-tissue procedures than orthopedic procedures. CLINICAL SIGNIFICANCE: Infiltration of surgical sites with liposomal bupivacaine seems safe in a broader range of orthopedic procedures than currently labeled. The results also justify further investigation in soft-tissue surgery.

CLINICAL EFFECTS OF HYPERBARIC LIDOCAINE AND BUPIVACAINE IN SPINAL ANESTHESIA - OUR EXPERIENCE.

Introduction: Various side effects and complications in the perioperative period can occur with the use of hyperbaric lidocaine and bupivacaine. Goal: Comparative presentation of the occurrence of side effects and complications of hyperbaric lidocaine and bupivacaine during spinal anesthesia in our patients. Methods: The study was retrospective and included 178 patients of both sexes. Patients were divided into two groups. In Group I (n-98) hyperbaric lidocaine 5% was used for spinal block. Group II (n-80) was divided into 2 subgroups, A- where hyperbaric Markain 0.5% was used (n-51), and B (n-29) where hyperbaric Sensorkain 0.75% was used. In the study, we analyzed gender, age, block onset, and complications. Results: There were 98 patients in Group I, 79 males and 19 females. There were 80 patients in Group II, 69 males and 11 females. The mean age of patients in Group I was 44.96 and in Group II 48.16 years. There was no statistically significant difference in the age of patients in both groups p> 0.05 (p = 0.2321). The occurrence of spinal block occurred significantly faster in Group I compared to group II (p <0.0001), and in subgroup B faster than in subgroup A (p <0.005). The clinical occurrence of complications and side effects during spinal anesthesia is somewhat more common in spinal block with 5% lidocaine. Conclusion: The compared incidence of adverse perioperative clinical effects and complications after administration of hyperbaric lidocaine and bupivacaine in spinal anesthesia was not statistically significant.

Changes in the microvascular reactivity during spinal anesthesia.

PURPOSE: Anesthesia alters microcirculation and tissue oxygen saturation (StO2). We sought to examine changes in StO2 using near-infrared spectroscopy and a vascular occlusion test (VOT) during spinal anesthesia. METHODS: This prospective observational study was included 51 patients without comorbidities who underwent elective surgery under spinal anesthesia. We measured the StO2 in the lower extremity during VOT before and after intrathecal injection. RESULTS: The baseline, minimum, and maximum StO2 values during VOT significantly increased after intrathecal injection (baseline StO2 from 68.6 ± 7.3% to 77.1 ± 10.1%, minimum StO2 from 39.7 ± 14.9% to 48.8 ± 17.6%, and maximum StO2 from 74.2 ± 7.5% to 80.2 ± 10.0%, all P < 0.0001). The occlusion slope and ischemic stimulus did not significantly change after intrathecal injection. The reperfusion slope was 1.38 ± 0.69%/sec before intrathecal injection and significantly decreased to 1.15 ± 0.61%/sec after intrathecal injection (P = 0.0001). CONCLUSIONS: Our results showed that despite an increased perfusion, reperfusion rate was significantly decreased by spinal anesthesia. Further studies are required to confirm how these contradictory results (improving oxygenation while reducing microvascular reactivity) actually affect the clinical impact of spinal anesthesia on microvascular function.

Exaggerated activities of TRPM7 underlie bupivacaine-induced neurotoxicity in the SH-SY5Y cells preconditioned with high glucose.

Hyperglycemia is considered a risk factor for the enhancement of local anesthetic-induced neurotoxicity. Transient receptor potential melastatin 7 (TRPM7), a kinase-coupled cation channel, has been implicated in a variety of neuropathological processes, including intracellular calcium disturbance and high glucose-induced neuropathy. In this study, we investigated whether TRPM7-related pathophysiology is involved in bupivacaine-induced neurotoxicity in SH-SY5Y cells and how hyperglycemia acts as a risk factor. For initial neurotoxicity evaluation, it was confirmed that cell damage and apoptosis induced by acute exposure to bupivacaine were dependent on its concentration and glucose preconditioning. High glucose preconditioning facilitated the bupivacaine-induced fast and temporary rise in intracellular free calcium concentration ([Ca2+ ]i ), which was attributed to both calcium influx through TRPM7 and calcium store release. Additionally, bupivacaine was shown to increase TRPM7-like currents, particularly in cells preconditioned with high glucose. Bupivacaine-induced neurotoxicity in hyperglycemia was correlated with extracellular signal-regulated kinase (ERK), but not protein kinase B (AKT) activation. Inhibition of TRPM7 and ERK activity alleviates bupivacaine neurotoxicity. These results suggest that therapeutically targeting TRPM7-related pathophysiological changes could be a potential strategy for treating local anesthetic-induced neurotoxicity exacerbated by hyperglycemia.

Hesperidin alleviates bupivacaine anesthesia-induced neurotoxicity in SH-SY5Y cells by regulating apoptosis and oxidative damage.

Local anesthetic with bupivacaine (BV) administration may cause severe neurotoxicity and neurological complications in developing neurons. Any substances that can mitigate the toxic effects of BV are of great importance in surgical procedures and pain management. The present study attempted to investigate if hesperidin (HN) could inhibit or prevent BV-induced neurotoxicity in SH-SY5Y cells. Exposure of BV at 5 mM resulted in a significant decrease of cell viability and a remarkable increase of lactate dehydrogenase release via the induction of apoptosis and production of reactive oxygen species. Moreover, a loss of mitochondrial membrane potential, decreased Bcl-2 protein expression, as well as increased expression of cytoplasmic cytochrome c, Bax, and cleaved caspase-3 protein was also observed in BV-stimulated SH-SY5Y cells. In addition, BV stimulation impaired the balance of oxidation-reduction and inflammation system, as evidenced by the increased malondialdehyde content, decreased superoxide dismutase and catalase activity, and reduced level of reduced glutathione, interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α. However, these iatrogenic changes were all reversed by the HN (5, 10, and 20 µM) supplement for 48 h in a concentration-dependent manner. In conclusion, HN can protect SH-SY5Y cells against BV-stimulated neurotoxicity via the inhibition of apoptosis, oxidative stress, and inflammation response. The present findings suggested that HN may be an effective alternative agent to inhibit or prevent BV-induced neurotoxicity in human patients.

Association Between Hyperbaric Bupivacaine Dose and Maternal Hypotension: Retrospective Database Study of 8226 Women Undergoing Cesarean Delivery Under Spinal Anesthesia.

BACKGROUND: Low-dose (≤8 mg) hyperbaric bupivacaine for spinal anesthesia during cesarean delivery results in reduced efficacy, yet as a secondary outcome was associated with reduced frequency of spinal-induced hypotension. Our primary aim was to investigate the relationship between hyperbaric bupivacaine dose and the occurrence of spinal-induced hypotension for cesarean delivery. METHODS: Retrospective study of cesarean delivery under spinal or combined spinal anesthesia with hyperbaric bupivacaine in 1 academic institution (2 centers-tertiary and district) from 2012 to 2018. Data were retrieved from the anesthesia information management systems (Metavision, iMDsoft, Tel Aviv, Israel) and the hospital information system, including potential confounding factors, maternal age and weight, hypertensive disease of pregnancy, single/multiple gestation, gestational age, vasopressor administration, planned/urgent surgery, position during anesthesia placement (sitting/lateral), and anesthesiologist seniority. Spinal-induced hypotension was defined as systolic blood pressure that either dropped >20% from baseline or <100 mm Hg. The primary outcome of interest was the incidence of spinal-induced hypotension according to hyperbaric bupivacaine dose. Logistic regression was used to characterize the association between the dose of hyberbaric bupivacaine and spinal-induced hypotension after adjusting for confounding factors. RESULTS: A total of 8226 women were identified. The hyperbaric bupivacaine dose administered was <9 mg for 2395 (29.1%), 9-9.5 mg for 1031 (12.5%), 10 mg for 4155 (50.5%), and >10 mg for 645 (7.8%). We used a cutoff (<10 vs ≥10 mg) to assess for the primary outcome, using multivariable logistic regression. The incidence of at least 1 spinal-induced hypotension episode was higher in patients who received ≥10 mg hyperbaric bupivacaine, 75.8% vs 62.9% for doses below 10 mg, P < .0001; however, even women with lower doses had hypotension. Hyperbaric bupivacaine dose <10 mg was associated with a lower incidence of spinal hypotension, adjusted odds ratio (OR) of 0.774, 95% confidence interval (CI), 0.669-0.897, and P = .0006, adjusted for confounding factors.Umbilical cord pH was available for 2684 (32.6%) cases. There were significantly more neonates with pH < 7.2, among women who received hyperbaric bupivacaine ≥10 mg (10.1%) versus women who received <10 mg (6.8%), P = .0032; however, in the adjusted model, hyperbaric bupivacaine dose ≥10 mg was not associated with pH < 7.2 and an OR of 0.955 (95% CI, 0.631-1.446, P = .829). CONCLUSIONS: Our major finding was that hypotension occurred at all doses of hyperbaric bupivacaine, yet occurrence of spinal hypotension was significantly associated with doses ≥10 mg after adjustment for potential confounders.

Comparison of the Analgesic Duration of 0.5% Bupivacaine With 1:200,000 Epinephrine Versus 0.5% Ropivacaine Versus 1% Ropivacaine for Low-Volume Ultrasound-Guided Interscalene Brachial Plexus Block: A Randomized Controlled Trial.

BACKGROUND: Bupivacaine and ropivacaine are the preferred long-acting local anesthetics for peripheral nerve blocks as they provide prolonged analgesia in the postoperative period. No studies have directly compared the analgesic duration of these commonly used local anesthetics in the setting of low-volume ultrasound-guided interscalene block (US-ISB). This study was designed to determine which local anesthetic and concentration provides superior analgesia (duration and quality) for low-volume US-ISB. METHODS: Sixty eligible patients scheduled for arthroscopic shoulder surgery were randomized (1:1:1) to receive US-ISB (5 mL) with 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine. All individuals were blinded including study participants, anesthesiologists, surgeons, research personnel, and statistician. All participants received a standardized general anesthetic and multimodal analgesia. The primary outcome was duration of analgesia defined as the time from the end of injection to the time that the patients reported a significant increase in pain (>3 numeric rating scale [NRS]) at the surgical site. RESULTS: The mean duration of analgesia for 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine was 14.1 ± 7.4, 13.8 ± 4.5, and 15.8 ± 6.3 hours, respectively (analysis of variance [ANOVA], P = .51). There were no observed differences in analgesic duration or other secondary outcomes between the 3 groups with the exception of a difference in cumulative opioid consumption up to 20h00 on the day of surgery in favor of ropivacaine 0.5% over bupivacaine of minimal clinical significance. CONCLUSIONS: In the context of single-injection low-volume US-ISB, we have demonstrated a similar efficacy between equal concentrations of ropivacaine and bupivacaine. In addition, increasing the concentration of ropivacaine from 0.5% to 1% did not prolong the duration of US-ISB.

Efficacy and Safety of a Surgeon-Performed Laparoscopic-Guided, 4-point Transversus Abdominis Plane Block: A retrospective review.

We performed a retrospective chart review from October 2017 to March 2019 to demonstrate the safety and efficacy of a surgeon-performed, laparoscopically guided, transversus abdominis plane (TAP) blocks for robot-assisted gynecologic procedures. A total of 116 patients who underwent robot-assisted gynecologic surgery, at 1 academic hospital, with administration of a 4-point TAP block were included. A 4-point TAP block was performed under laparoscopic visualization, by the same surgeon, after induction of anesthesia and immediately after placement of the laparoscope. Liposomal bupivacaine (20 mL) and 0.5% bupivacaine (20 mL) mixed with saline were used as the injectant. All information from the surgical admission and the postoperative follow-up were reviewed. Data were presented in our descriptive study. A total of 116 patients were included with a mean age of 40.6 years (19-80 years) and a mean body mass index of 30.6 kg/m2 (17.2-53.3 kg/m2). Of the patients, 70.7% were discharged to home on the day of surgery. Of the 29.3% of patients who were admitted, 20.6% were admitted because of pain control. Those who were admitted for pain control comprised 6.0% of the total of all study participants. There were no adverse events in our cohort and no readmissions because of pain control. A surgeon-performed TAP block, under laparoscopic visualization, is a safe and efficacious intervention to reduce postoperative pain and may add to a multimodal approach for enhanced recovery protocols.

Pharmacokinetics and safety of liposomal bupivacaine after local infiltration in healthy Chinese adults: a phase 1 study.

BACKGROUND: Liposomal bupivacaine (LB) is a long-acting formulation of bupivacaine. The safety and efficacy of LB has been demonstrated across surgical procedures. However, pharmacokinetic (PK) parameters and safety of LB in the Chinese population have not been assessed. METHODS: In this single-arm, single center, phase 1, open-label study, PK and safety of local infiltration with LB 266 mg were assessed in healthy Chinese adults. Eligible participants were aged 18 to 55 years with biologic parents and grandparents of Chinese ethnicity, in generally good health (i.e., no clinically significant abnormalities), and with a body mass index (BMI) 19.0 to 24.0 kg/m2 (inclusive) and body weight ≥ 50 kg. RESULTS: Participants (N = 20) were predominantly men (80 %); mean age was 32 years; and mean BMI was 21.8 kg/m2. After LB administration, mean plasma levels of bupivacaine rapidly increased during the first hour and continued to increase through 24 h; plasma levels then gradually decreased through 108 h followed by a monoexponential decrease through 312 h. Geometric mean maximum plasma concentration was 170.9 ng/mL; the highest plasma bupivacaine concentration detected in any participant was 374.0 ng/mL. Twenty-two treatment-emergent adverse events were reported (mild, n = 21; moderate, n = 1). CONCLUSIONS: After single-dose administration of LB, PK measures were similar to a previously reported profile in US adults. The highest observed peak plasma concentration of bupivacaine was several-fold below the plasma concentration threshold accepted as being associated with neurotoxicity or cardiotoxicity (2000-4000 ng/mL). These data support that LB is well tolerated and safe in individuals of Chinese descent. TRIAL REGISTRATION: NCT04158102 (ClinicalTrials.gov identifier), Date of registration: November 5, 2019.