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.

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.

Evaluation of the New SingularityTM Air versus Ambu® Aura GainTM: A Randomized, Crossover Mannequin Study.

Background: This randomised crossover mannequin study aimed to compare the insertion time for the newly developed SingularityTM Air and the Ambu® AuraGainTM. The SingularityTM Air includes a bendable tube in order to allow optimal passform. Methods: Fifty anaesthetists with a minimum of 100 supraglottic airway device insertions were recruited and randomly assigned to start either with the SingularityTM Air or with the Ambu® AuraGainTM. Participants watched a tutorial video the day before the assessment and received a standardized introduction immediately before the assessment. The primary outcome was the time for successful insertion. Secondary parameters were the overall insertion success rate, the numbers of insertion attempts (maximum three), the glottic view through a flexible bronchoscope, and the success rate for gastric tube insertion. Results: Fifty participants were eventually recruited and randomly assigned to insert both devices according to the randomization. The insertion time was 24 s for SingularityTM Air as compared to 20 s for Ambu® AuraGainTM (p < 0.001). Overall insertion rate was 92% for the SingularityTM Air as compared to 100% for the Ambu® AuraGainTM (p could not be derived as one variable is a constant). The primary insertion success rate was better for the Ambu® AuraGainTM than for the SingularityTM Air (94% versus 68%; p: 0.002, respectively). Conclusion: The time for successful insertion and the insertion success rate for the newly developed SingularityTM Air is inferior to that for the Ambu® AuraGainTM.

WITHDRAWN: Comment on "Comparison of the clinical performance of the i-gelTM, LMA SupremeTM, and Ambu AuraGainTM in adult patients during general anesthesia: a prospective and randomized study"

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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 impact of dexamethasone as a perineural additive to ropivacaine for PECS II blockade in patients undergoing unilateral radical mastectomy - A prospective, randomized, controlled and double-blinded trial.

STUDY OBJECTIVE: Dexamethasone is commonly used as an adjuvant to local anesthetics to prolong duration of peripheral nerve blocks with minimal side-effects. The present study investigates the efficacy of dexamethasone added to ropivacaine 0.2% as compared to ropivacaine 0.2% alone for pectoral nerves block II (PECS II) in unilateral radical mastectomy. DESIGN: A prospective, randomized, controlled and double-blinded trial. SETTING: The study was performed at Innsbruck Medical University Hospital, Austria, between January 2019 and October 2020. PATIENTS: Sixty female patients with an American Society of Anesthesiologists Score I-II (18-90 years, BMI 18-35) scheduled for unilateral radical mastectomy without one-stage immediate autologous breast reconstruction were randomly assigned to receive PECS II block with ropivacaine 0.2% with or without dexamethasone 8 mg. INTERVENTIONS: Patients were randomly assigned to receive PECS II block with ropivacaine 0.2% with or without dexamethasone 8 mg. MEASUREMENTS: Primary outcome parameter was the cumulative opioid consumption during the first 72 postoperative hours. Secondary outcome parameters were the duration of analgesia and the course of the visual analogue scale (VAS) and the area under the curve VAS (AUC-VAS). MAIN RESULTS: There was no difference in cumulative opioid consumption after 72 h between the ropivacaine 0.2% plus dexamethasone group and the ropivacaine 0.2% plus placebo group (11.89 vs 11.90 morphine milligram equivalent, respectively; p 0.831). Duration of analgesia also did not differ significantly between the ropivacaine 0.2% plus dexamethasone group and the ropivacaine 0.2% plus placebo group (12.75 versus 8.75 h, respectively; p 0.680). There also was no difference in the course of VAS and AUC-VAS. CONCLUSIONS: Dexamethasone 8 mg when added to ropivacaine 0.2% for PECS II block in unilateral radical mastectomy was not found to reduce total opioid consumption over 72 postoperative hours or to prolong duration of analgesia as compared to pure ropivacaine 0.2%.