Crystallization of mixtures of local anesthetics with and without select adjuvants: a semiquantitative light microscopy analysis.

INTRODUCTION: Injecting mixtures of local anesthetics with or without adjuvants is a common practise in regional and particularly obstetric anesthesia to decrease block onset time and/or augment epidural analgesia for cesarean section. While evidence on the efficacy of this practise is equivocal, little is known about its safety in terms of the pharmacologic compatibility of local anesthetics. METHODS: We assessed the grade of crystallization in individual mixtures of seven local anesthetics (bupivacaine, ropivacaine, lidocaine, procaine, chloroprocaine, mepivacaine, prilocaine) with or without four adjuvants (sodium bicarbonate, dexamethasone, clonidine, fentanyl) using a semiquantitative light microscopy scale (ranging from 0 to 5), repeatedly for up to 60 min and performed correlation analysis between grade of crystallization and initial solution pH. RESULTS: Of the 50 mixtures tested, 26 showed grades of crystallization ≥4 at admixture and 41 showed grades of crystallization ≥4 after 60 min. The addition of adjuvants to local anesthetic mixtures did not substantially change the grades of crystallization. Bupivacaine has a slightly lower precipitation tendency, compared with ropivacaine. A moderate relationship was found between initial pH and grade of crystallization after 15 min for the adjuvant mixtures (R=0.33, p=0.04), but not at other time points. DISCUSSION: The preparation of local anesthetic (±adjuvant) mixtures leads to high grades of crystallization, which increase over 60 min and appear independent of solution pH. The risk of mixing medications with unknown physical or chemical compatibility profiles in regional anesthesia should be critically appraised and its clinical significance elucidated in future translational research.

Trends of liposomal bupivacaine utilization in major lower extremity total joint arthroplasty in the USA: a population-based study.

INTRODUCTION: Liposomal bupivacaine has been marketed for the achievement of long-acting local or regional anesthesia after major lower extremity total joint arthroplasty. However, it is comparatively expensive and controversy remains regarding its ability to decrease healthcare costs. With mounting evidence suggesting non-superiority in efficacy, compared with plain bupivacaine, we sought to investigate trends in liposomal bupivacaine use and identify changes in practice. METHODS: We identified adult patients from the Premier Healthcare Database who underwent elective total joint arthroplasty between 2012 and 2021. Prevalence and trends of liposomal bupivacaine utilization were compared on the individual patient and hospital levels. Log-rank tests were performed to assess the influence of location, teaching status, or hospital size on time to hospital-level liposomal bupivacaine termination. RESULTS: Among 103,165 total joint arthroplasty cases, liposomal bupivacaine use increased between 2012 and 2015 (from 0.4% to 22.8%) and decreased by approximately 1%-3% annually thereafter (15.7% in 2021). Liposomal bupivacaine was ever used in approximately 60% of hospitals. Hospital-level initiation of liposomal bupivacaine use peaked in 2014 and decreased thereafter (from 32.8% in 2013 to 4.3% in 2021), while termination rates increased (from 1.4% in 2014 to 9.9% in 2019). Non-teaching hospitals and those located in the South and West regions were more likely to retain liposomal bupivacaine longer than teaching or Midwest/Northeast hospitals, respectively (p=0.023 and p=0.014). DISCUSSION: Liposomal bupivacaine use peaked around 2015 and has been declining thereafter on individual patient and hospital levels. How these trends correlate with health outcomes and expenditures would be a strategic target for future research.

The impact of PECS II blockade in patients undergoing minimally invasive cardiac surgery-a prospective, randomized, controlled, and triple-blinded trial.

BACKGROUND: Classic neuraxial techniques, such as thoracic epidural anesthesia, or alternative approaches like the paravertebral block, are not indicated in cardiac surgery due to increased bleeding risk. To provide satisfactory analgesia without the need for excessive opioid use, novel ultrasound techniques gained popularity and are of growing interest. The pectoralis nerve block II (PECS II) has been shown to provide good postoperative analgesia in modified radical mastectomy and might also be suitable for minimally invasive cardiac surgery. METHODS: In a single center, prospective, triple-blinded, two-group randomized trial, 60 patients undergoing elective, unilateral minimal invasive cardiac surgery will be randomized to receive a PECS II with 30 ml of ropivacaine 0.5% (intervention group) or sodium chloride 0.9% (placebo group). The primary outcome parameter is the overall opioid demand given as intravenous morphine milligram equivalents (MME) during the first 24 h after extubation. Secondary endpoints are the visual analog scale (VAS) 2, 4, 6, 8, 12, and 24 h after extubation, the Overall Benefit of Analgesia Score (OBAS) after 24 h, the interval until extubation, and intensive care unit (ICU) discharge within 24 h, as well as the length of hospital stay (LOS). DISCUSSION: This prospective randomized, controlled, and triple-blinded trial aims to assess if a PECS II with ropivacaine 0.5% helps to decrease the opioid demand in the first 24 h and increases postoperative pain control after minimally invasive cardiac surgery. TRIAL REGISTRATION: www.clinicaltrialsregister.eu ; EudraCT Nr: 2021-005452-11; Lukas Gasteiger MD, November 18, 2021.

Academic anaesthesiology: a global perspective on training, support, and future development of early career researchers.

As anaesthesiologists face increasing clinical demands and a limited and competitive funding environment for academic work, the sustainability of academic anaesthesiologists has never been more tenuous. Yet, the speciality needs academic anaesthesiologists in many roles, extending beyond routine clinical duties. Anaesthesiologist educators, researchers, and administrators are required not only to train future generations but also to lead innovation and expansion of anaesthesiology and related specialities, all to improve patient care. This group of early career researchers with geographically distinct training and practice backgrounds aim to highlight the diversity in clinical and academic training and career development pathways for anaesthesiologists globally. Although multiple routes to success exist, one common thread is the need for consistent support of strong mentors and sponsors. Moreover, to address inequitable opportunities, we emphasise the need for diversity and inclusivity through global collaboration and exchange that aims to improve access to research training and participation. We are optimistic that by focusing on these fundamental principles, we can help build a more resilient and sustainable future for academic anaesthesiologists around the world.

COVID-19 Pandemic Did not Influence Number of Oncologic and Emergency Surgeries: A Retrospective Cohort Study from a Tertiary Hospital in Austria.

BACKGROUND: Many articles described a massive decline in surgical procedures during the COVID-19 pandemic waves. Especially the reduction in oncologic and emergency procedures led to the concern that delays and cancelling surgical activity might lead to a substantial increase in preventable deaths. METHODS: Overall numbers and types of surgery were analysed in a tertiary hospital in Austria during the winter period (October-April) from 2015/16 to 2021/22. The half-years 2019/20, 2020/21 and 2021/22 were defined as pandemic half-years and were compared with the mean results of the previous, four, pre-pandemic half-years. RESULTS: A reduction was found for overall numbers and elective surgeries during 2019/20 (4.62%; p < 0.0001 and 12.14; p < 0.0001 respectively) and 2021/22 (14.94%; p < 0.0001 and 34.27; p < 0.0001 respectively). Oncologic surgery increased during 2021/22 (- 12.59%; p < 0.0001) and remained unchanged during the other periods. Emergency surgeries increased during 2019/20 (- 6.97%; p < 0.0001) and during 2021/22 (- 9.44%; p < 0.0001) and remained unchanged during 2020/21. CONCLUSIONS: The concern that the pandemic led to a decrease in oncologic and emergency surgeries cannot be supported with the data from our hospital. A flexible, day-by-day, resource allocation programme with central coordination adhering to hospital resilience recommendations may have helped to adapt to the impact of the COVID-19 pandemic during the first three pandemic half-years.

Crystallization of short-acting and intermediate-acting local anesthetics when mixed with adjuvants: a semiquantitative light microscopy analysis.

INTRODUCTION: The addition of adjuvants to short-acting local anesthetics (LA) is common practice in clinical routine to speed up block onset and decrease pain on injection. In a previous study, we observed the development of microscopic crystal precipitations after bupivacaine or ropivacaine were mixed with adjuvants; this follow-up study is intended to clarify whether crystallization (A) also occurs in short-acting or intermediate-acting LA-adjuvant mixtures, (B) changes over time, and (C) is associated with the solutions' pH. METHODS: Lidocaine 2%, prilocaine 2%, mepivacaine 2%, procaine 2% and chloroprocaine 2% were individually mixed with clonidine, dexamethasone, dexmedetomidine, epinephrine, fentanyl, morphine or sodium bicarbonate 8.4% in clinically established ratios. For each mixture, we measured initial pH and recorded crystallization patterns at 0, 15, 30 and 60 min using a standardized, semiquantitative light microscopy approach. RESULTS: Lidocaine 2% and mepivacaine 2% plus sodium bicarbonate 8.4%, and mepivacaine 2% plus dexamethasone developed delayed grade 5 crystallization over 1 hour. Prilocaine-based, procaine-based and chloroprocaine-based mixtures showed much less pronounced crystallization, with a maximum of grade 2. Initial pH and grade of crystallization showed weak monotonic relationships at time points t0, t15 and t30 (ρ=-0.17, 0.31 and 0.32, (all p>0.05)) and a moderate relationship time point t60 (ρ=0.57 (p=0.0003)) CONCLUSIONS: Our study revealed high grades of crystallization in lidocaine/mepivacaine-bicarbonate and mepivacaine-dexamethasone mixtures, although these were previously considered safe for local, perineural or neuraxial use. Our findings cast particular doubt on the safety of preparing these formulations for later use.

Peripheral Regional Anesthesia Using Local Anesthetics: Old Wine in New Bottles?

During the past decade, numerous efforts were undertaken aiming at prolonging the analgesic effect of regional anesthesia. With the development of extended-release formulations and enhanced selectivity for nociceptive sensory neurons, a very promising contribution to the development of pain medications has been achieved. At present, liposomal bupivacaine is the most popular, non-opioid, controlled drug delivery system, but its duration of action, which is still controversially discussed, and its expensiveness have decreased initial enthusiasm. Continuous techniques can be seen as an elegant alternative for providing a prolonged duration of analgesia, but for logistic or anatomical reasons, they are not always the best choice. Therefore, focus has been directed towards the perineural and/or intravenous addition of old and established substances. As for perineural application, most of these so-called 'adjuvants' are used outside their indication, and their pharmacological efficacy is often not or only poorly understood. This review aims to summarize the recent developments for prolonging the duration of regional anesthesia. It will also discuss the potential harmful interactions and side effects of frequently used analgesic mixtures.

Minimally Invasive Approaches for Traumatic Rupture of the Pancreas in Children-A Case Series.

Pancreatic trauma in children is rare; therefore, both scientific knowledge and clinical experience regarding its management are limited. Abdominal sonography and subsequent computed tomography (CT) imaging are the diagnostic mainstay after severe abdominal trauma in many pediatric trauma centers. However, the diagnosis of pancreatic injury is missed on the initial imaging in approximately one third of cases, with even higher numbers in young children. While conservative treatment is preferred in low-grade injuries, surgical interventions may be indicated in more severe injuries. We present a case series including four patients with high-grade pancreatic injury. Two patients were treated surgically with open laparotomy and primary suture of the head of the pancreas and pancreatico-enterostomy, one patient underwent endoscopic stenting of the pancreatic duct and one received conservative management including observation and secondary endoscopic treatment. We want to emphasize the fact that using a minimally invasive approach can be a feasible option in high-grade pancreatic injury in selected cases. Therefore, we advocate the necessity of fully staffed and equipped high-level pediatric trauma centers.

Improving Safety of Bilateral Knee Arthroplasty: Impact of Selection Criteria on Perioperative Outcome.

Background: Bilateral total knee arthroplasty (BTKA) procedures are associated with an increased risk of complications when compared with unilateral approaches. In 2006, in an attempt to reduce this risk, our institution implemented selection criteria that specified younger and healthier patients as candidates for BTKA. Questions/Purpose: We sought to investigate the effect of these selection criteria on perioperative outcomes. Methods: In a retrospective cohort study, we used institutional data to identify patients who underwent BTKA between 1998 and 2014. Patients were divided into 2 groups: those who underwent surgery before the 2006 introduction of our selection criteria (1998-2006) and those who underwent surgery after (2007-2014). Groups were compared in terms of demographics, comorbidity burden, and incidence of perioperative complications. Regression analysis was performed, calculating incidence rate ratios to evaluate changes in complication rates. Results: Before the selection criteria were implemented in 2006, patients who underwent BTKA were older and had a higher comorbidity burden. The rate of major complications per 1000 hospital days decreased from 31.5 in 1998 to 7.9 in 2014. A reduction in cardiac complications was the most significant contributor to this decrease in major complications. Conclusion: After stringent criteria for BTKA candidates were implemented at our institution, selection of younger patients with lower comorbidity burden was accompanied by a reduction in the incidence of operative complications. This suggests that introducing such criteria can be associated with a reduction in adverse perioperative outcomes.

Crystallization of ropivacaine and bupivacaine when mixed with different adjuvants: a semiquantitative light microscopy analysis.

INTRODUCTION: Amino-amide local anesthetics precipitate when mixed with some commonly used adjuvants, carrying the risk of perineural or vascular crystal deposition. The aim of this study was to evaluate whether crystallization occurs with routinely used local anesthetic-adjuvant combinations and if a relation with the solution's pH exists. METHODS: All substances used in this trial were first visually investigated undiluted under tenfold magnification. Grade of crystallization was assessed using a 6 point grading system.Ropivacaine (0.2%, 0.75% and 1%) and bupivacaine (0.25% and 0.5%) were mixed in a 1:1 solution with the following adjuvants: dexamethasone, dexmedetomidine, clonidine, fentanyl, sodium bicarbonate 8.4% and sodium chloride 0.9%. Subsequently, ropivacaine (0.2% and 0.75%) and bupivacaine (0.25% and 0.5%) were mixed with adjuvants in concentrations commonly used in clinical practice and then serially assessed at several time points up to 1 hour. pH of all substances/combinations was assessed and correlated with crystallization grade. RESULTS: All pure substances-except the reference standards sterile water and triamcinolon-showed crystallization grades ranging from grade 1 to grade 4. Addition of adjuvants lead to variable, unpredictable changes in crystal depositions. Addition of sodium bicarbonate 8.4% produced heavy crystallization in all combinations. Grade of crystallization was weakly positively related to the pH of the solution in 1:1 mixtures and clinically relevant concentrations, but not in pure substances. DISCUSSION: Our study showed that crystallization is present in pure local anesthetics and may be increased or decreased by admixture of adjuvants. Higher pH of mixtures was weakly associated with more crystallization. Further research is necessary to translate these findings into clinical practice.

The 'long shadow' of perioperative complications: association with increased risk of death up to one year after surgery.

Thirty-day mortality is widely used in medical and surgical outcomes research as a quality indicator, and as an endpoint in perioperative clinical trials. However, the validity of this metric has recently been questioned. In this issue of the British Journal of Anaesthesia, Fowler and colleagues quantify, update, and put into perspective the looming suspicion that perioperative adverse events cast a 'long shadow' of increased mortality, far beyond the 30-day time frame. Their work not only raises important questions on how we should think about, analyse, and report 'perioperative' complications and mortality, but also stresses anaesthesiologist and surgeon roles as key stakeholders in patient long-term survival.

Association between use of enhanced recovery after surgery protocols and postoperative complications in colorectal surgery in Europe: The EuroPOWER international observational study.

STUDY OBJECTIVE: Assess the relationship between the Enhanced Recovery After Surgery (ERAS®) pathway and routine care and 30-day postoperative outcomes. DESIGN: Prospective cohort study. SETTING: European centers (185 hospitals) across 21 countries. PATIENTS: A total of 2841 adult patients undergoing elective colorectal surgery. Each hospital had a 1-month recruitment period between October 2019 and September 2020. INTERVENTIONS: Routine perioperative care. MEASUREMENTS: Twenty-four components of the ERAS pathway were assessed in all patients regardless of whether they were treated in a formal ERAS pathway. A multivariable and multilevel logistic regression model was used to adjust for baseline risk factors, ERAS elements and country-based differences. RESULTS: A total of 1835 patients (65%) received perioperative care at a self-declared ERAS center, 474 (16.7%) developed moderate-to-severe postoperative complications, and 63 patients died (2.2%). There was no difference in the primary outcome between patients who were or were not treated in self-declared ERAS centers (17.1% vs. 16%; OR 1.00; 95%CI, 0.79-1.27; P = 0.986). Hospital stay was shorter among patients treated in self-declared ERAS centers (6 [5-9] vs. 8 [6-10] days; OR 0.82; 95%CI, 0.78-0.87; P < 0.001). Median adherence to 24 ERAS elements was 57% [48%-65%]. Adherence to ERAS-pathway quartiles (≥65% vs. <48%) suggested that patients with the highest adherence rates experienced a lower risk of moderate-to-severe complications (15.9% vs. 17.8%; OR 0.71; 95%CI, 0.53-0.96; P = 0.027), lower risk of death (0.3% vs. 2.9%; OR 0.10; 95%CI, 0.02-0.42; P = 0.002) and shorter hospital stay (6 [4-8] vs. 7 [5-10] days; OR 0.74; 95%CI, 0.69-0.79; P < 0.001). CONCLUSIONS: Treatment in a self-declared ERAS center does not improve outcome after colorectal surgery. Increased adherence to the ERAS pathway is associated with a significant reduction in overall postoperative complications, lower risk of moderate-to-severe complications, shorter length of hospital stay and lower 30-day mortality.

Differential Perioperative Outcomes in Patients With Obstructive Sleep Apnea, Obesity, or a Combination of Both Undergoing Open Colectomy: A Population-Based Observational Study.

BACKGROUND: An increasing body of evidence demonstrates an association between obstructive sleep apnea (OSA) and adverse perioperative outcomes. However, large-scale data on open colectomies are lacking. Moreover, the interaction of obesity with OSA is unknown. This study examines the impact of OSA, obesity, or a combination of both, on perioperative complications in patients undergoing open colectomy. We hypothesized that while both obesity and OSA individually increase the likelihood for perioperative complications, the overlap of the 2 conditions is associated with the highest risk. METHODS: Patients undergoing open colectomies were identified using the national Premier Healthcare claims-based Database (2006-2016; n = 340,047). Multilevel multivariable models and relative excess risk due to interaction (RERI) analysis quantified the impact of OSA, obesity, or both on length and cost of hospitalization, respiratory and cardiac complications, intensive care unit (ICU) admission, mechanical ventilation, and inhospital mortality. RESULTS: Nine thousand twenty-eight (2.7%) patients had both OSA and obesity diagnoses; 10,137 (3.0%) had OSA without obesity; and 33,692 (9.9%) had obesity without OSA. Although there were overlapping confidence intervals in the binary outcomes, the risk increase was found highest for OSA with obesity, intermediate for obesity without OSA, and lowest for OSA without obesity. The strongest effects were seen for respiratory complications: odds ratio (OR), 2.41 (2.28-2.56), OR, 1.40 (1.31-1.49), and OR, 1.50 (1.45-1.56), for OSA with obesity, OSA without obesity, and obesity without OSA, respectively (all P < .0001). RERI analysis revealed a supraadditive effect of 0.51 (95% confidence interval [CI], 0.34-0.68) for respiratory complications, 0.11 (-0.04 to 0.26) for cardiac complications, 0.30 (0.14-0.45) for ICU utilization, 0.34 (0.21-0.47) for mechanical ventilation utilization, and 0.26 (0.15-0.37) for mortality in patients with both OSA and obesity, compared to the sum of the conditions' individual risks. Inhospital mortality was significantly higher in patients with both OSA and obesity (OR [CI], 1.21 [1.07-1.38]) but not in the other groups. CONCLUSIONS: Both OSA and obesity are individually associated with adverse perioperative outcomes, with a supraadditive effect if both OSA and obesity are present. Interventions, screening, and perioperative precautionary measures should be tailored to the respective risk profile. Moreover, both conditions appear to be underreported compared to the general population, highlighting the need for stringent perioperative screening, documentation, and reporting.

Regional anesthesia and pain management in patients with sleep apnea: can they improve outcomes?

PURPOSE OF REVIEW: In several guidelines, regional anesthesia and analgesia have been suggested as safer alternatives for general anesthesia and systemic analgesia for their safety profile in patients suffering from obstructive sleep apnea (OSA). However, the underlying scientific basis is still evolving. The present review is intended to provide an up-to-date account on the question whether the use of regional anesthesia improves outcomes in patients with OSA. RECENT FINDINGS: A number of studies found favorable effects of regional anesthesia used in patients with OSA, including reduced incidence of major perioperative complications such as the need for mechanical ventilation, reintubation and pulmonary/cardiac complications. No negative effects of regional anesthesia specific to patients with OSA were found. Regional anesthesia was most effective when used as a sole technique, but also carried benefits when added to general anesthesia. The majority of available literature focuses on orthopedic surgery and neuraxial anesthesia. SUMMARY: Regional anesthesia can be recommended as a good strategy to treat patients with OSA whenever feasible, as it reduces the incidence of potentially catastrophic perioperative complications. However, the breadth of both surgical and regional anesthetic techniques analyzed is limited; further research should focus on extending the knowledge base beyond neuraxial anesthesia and orthopedics.

Effectiveness of intravenous acetaminophen for postoperative pain management in hip and knee arthroplasties: a population-based study.

BACKGROUND AND OBJECTIVES: The significance of intravenous over oral acetaminophen (APAP) as part of multimodal analgesic protocols is contested, particularly when considering its relatively high price and use in a surgical cohort such as total hip or knee arthroplasty (THA/TKA), which generally tolerates oral medications. This study aims to elucidate APAP's effectiveness in a large, population-based patient sample. METHODS: 1 039 647 THA/TKA procedures were sampled from the Premier Healthcare claims database 2011-2016. APAP use was categorized by intravenous/oral and use on the day of surgery, postoperative day 1 and thereafter. Outcomes were opioid utilization (in oral morphine equivalents), length and cost of hospitalization, and opioid-related adverse effects (respiratory, gastrointestinal, and naloxone use as a proxy). Mixed-effects models measured the associations between intravenous/oral APAP use and outcomes. Percent (%) change and 95% CIs are reported. RESULTS: Overall, 23.6% (n=245 454) of patients received intravenous APAP; of these, 56.3% (n=138 180) received just one dose on the day of surgery. After adjustment for relevant covariates, particularly use of >1 dose of intravenous APAP (compared with no use) on postoperative day 1 was associated with -6.0% (CI -7.2% to -4.7%) reduced opioid utilization; this was -10.7% (CI -11.4% to -9.9%) for use of > 1 dose oral APAP on postoperative day 1. Further comparisons regarding other outcomes also favored oral (over intravenous) APAP. CONCLUSIONS: These results do not support the routine use of intravenous APAP in patients undergoing lower joint arthroplasty, especially since oral APAP shows more beneficial outcome patterns.

Changes in the augmentation index and postoperative orthostatic intolerance in orthopedic surgery: a prospective cohort study.

BACKGROUND: Postoperative orthostatic intolerance (OI) can be a major obstacle to early ambulation and its determinants are poorly understood. We aimed to study postoperative changes in vascular tone and their potential association with OI in various orthopedic surgical settings. METHODS: In this prospective cohort study, 350 patients undergoing total joint arthroplasty under neuraxial anesthesia or spine surgery under general anesthesia were enrolled. We determined the augmentation index (AI) as a measure of vascular tone and studied symptoms of OI using a validated questionnaire at various postoperative time points. RESULTS: The AI was significantly reduced postoperatively (at spinal resolution in patients with neuraxial anesthesia or two hours postoperatively in general anesthesia) compared with baseline values in all procedures and did not subsequently return to baseline throughout the postoperative period in the majority of patients [252/335 (75.2%); P < 0.001]. The majority [260/342 (76.0%); P < 0.001] of patients had postoperative symptoms of OI. Nevertheless, no association was found between postoperative change in AI from baseline and postoperative symptoms of OI. CONCLUSIONS: A significantly prolonged decrease in AI and symptoms of OI are common after orthopedic surgery. Nevertheless, an association between the two measures was not observed. While compensatory mechanisms may limit the influence of an AI decrease on symptoms of OI, more research is needed to understand the contributing factors and aid in the identification of patients at risk of OI.