Optimizing neuromuscular blockade management for improving patient safety and peri-operative outcomes: a pilot phase of a quality improvement initiative.

INTRODUCTION: Although quantitative monitoring of neuromuscular blockade (NMB) is recommended, it is not routinely used in daily practice. The optimizing NMB management to improve patient safety and perioperative outcomes (OBISPO) quality improvement (QI) initiative intends to address this issue and change clinicians' behaviors. MATERIAL AND METHODS: A pilot phase of the prospective QI intervention was conducted. The primary objective was implement clinical practice change that emphasizes improving NMB monitoring in patients undergoing elective cardiac surgery who are eligible for fast-track extubation between February 2021 and December 2021. The secondary objective was to reduce the train-of-four ratio (TOFR) < 0.9 incidence before tracheal extubation to less than 20%. The intervention included educational sessions for teams. RESULTS: A total of 859 patients underwent elective cardiac surgery, 40% were eligible for fast-track extubation. From our cohort of fast-track cardiac cases, 69% had reported TOFR; 47% of them had residual paralysis (TOFR < 0.9) on arrival to PACU, 22% persisted with residual paralysis after extubation, and 27% were extubated without monitoring. The survey identified cognitive biases, knowledge gaps, unfamiliarity, and lack of trust in quantitative monitoring devices. Workflow disruptions imposed by COVID and changes in NMB monitoring devices have negatively affected our initiative. CONCLUSIONS: Our study showed that changes in clinician behavior are among the most challenging issues in perioperative medicine. Continuous teaching and QI initiatives, focused on quantitative NMB monitors and adequate reversal agent use, are mandatory to improve perioperative outcomes. Therefore, new proposals are required to promote changes in current practices.

Erector spinae plane block, neuropathic pain and quality of life after video-assisted thoracoscopy surgery. Pilot, observational study.

BACKGROUND: The erector spinae plane block (ESPB) is a valuable alternative for pain management after video-assisted thoracoscopy surgery (VATS). The incidence of postoperative chronic neuropathic pain (CNP) is high while the quality of life (QoL) after VATS remains unknown. We hypothesised that patients with ESPB would have a low incidence of acute and CNP and would report a good QoL up to three months after VATS. METHODS: We conducted a single-centre prospective pilot cohort study from January to April 2020. ESPB after VATS was the standard practice. The primary outcome was the incidence of CNP three months postoperatively. Secondary outcomes included QoL assessed by the EuroQoL questionnaire three months after surgery and pain control at the Post-Anaesthesia Care Unit (PACU), 12 and 24 hours postoperatively. RESULTS: We conducted a single-centre prospective pilot cohort study from January to April 2020. ESPB after VATS was the standard practice. The primary outcome was the incidence of CNP three months postoperatively. Secondary outcomes included QoL assessed by the EuroQoL questionnaire three months after surgery and pain control at the Post-Anaesthesia Care Unit (PACU), 12 and 24 hours postoperatively. CONCLUSIONS: We conducted a single-centre prospective pilot cohort study from January to April 2020. ESPB after VATS was the standard practice. The primary outcome was the incidence of CNP three months postoperatively. Secondary outcomes included QoL assessed by the EuroQoL questionnaire three months after surgery and pain control at the Post-Anaesthesia Care Unit (PACU), 12 and 24 hours postoperatively.

Therapeutic drug monitoring of tranexamic acid in plasma and urine of renally impaired patients using solid phase microextraction.

The purpose of the research was to develop an improved solid phase microextraction (SPME)-based sampling protocol for the therapeutic drug monitoring of tranexamic acid (TXA) from plasma and urine of patients with chronic renal dysfunction (CRD) in order to correct the current dosing schedule to accommodate these patients. A 12-fold improvement in sampling efficiency (25 min for 96 samples -22 s per sample) was achieved with the use of hydrophilic-lipophilic balance (HLB)-coated SPME devices, thereby enabling high throughput profiling of TXA in the plasma and urine of 49 CRD patients undergoing cardiac surgery. A limit of quantification of 10 µg/mL and 25 µg/mL was obtained for plasma and urine respectively while a method accuracy of 103-105% and a precision of less than 8% was achieved. The results from this study were ultimately used by clinicians at the Toronto General Hospital to design a corrective pharmacokinetic dosing schedule for CRD patients. This green method further presents potential application in the clinical field for the fast high throughput monitoring of TXA not only in plasma but also in urine - a biological matrix seldom explored for the analysis of TXA - without the need for solvent-assisted extraction, extensive sample pre-treatment or clean-up, derivatization or excessive pH adjustment to improve amenability for analytical separation.

Untargeted metabolomics profiling of skeletal muscle samples from malignant hyperthermia susceptible patients.

PURPOSE: Malignant hyperthermia (MH) is a potentially fatal hypermetabolic condition triggered by certain anesthetics and caused by defective calcium homeostasis in skeletal muscle cells. Recent evidence has revealed impairment of various biochemical pathways in MH-susceptible patients in the absence of anesthetics. We hypothesized that clinical differences between MH-susceptible and control individuals are reflected in measurable differences in myoplasmic metabolites. METHODS: We performed metabolomic profiling of skeletal muscle samples from MH-negative (control) individuals and MH-susceptible patients undergoing muscle biopsy for diagnosis of MH susceptibility. Cellular metabolites were extracted from 33 fresh and 87 frozen human muscle samples using solid phase microextraction and Metabolon® untargeted biochemical profiling platforms, respectively. Ultra-performance liquid chromatography-high resolution mass spectrometry was used for metabolite identification and validation, followed by analysis of differences in metabolites between the MH-susceptible and MH-negative groups. RESULTS: Significant fold-change differences between the MH-susceptible and control groups in metabolites from various pathways were found (P value range: 0.009 to < 0.001). These included accumulation of long chain acylcarnitines, diacylglycerols, phosphoenolpyruvate, histidine pathway metabolites, lysophosphatidylcholine, oxidative stress markers, and phosphoinositols, as well as decreased levels of monoacylglycerols. The results from both analytical platforms were in agreement. CONCLUSION: This metabolomics study indicates a shift from utilization of carbohydrates towards lipids for energy production in MH-susceptible individuals. This shift may result in inefficiency of beta-oxidation, and increased muscle protein turnover, oxidative stress, and/or lysophosphatidylcholine levels.

RéSUMé: OBJECTIF : L'hyperthermie maligne (HM) est une condition hypermétabolique potentiellement mortelle déclenchée par certains agents anesthésiques et causée par une homéostasie calcique perturbée des cellules musculaires squelettiques. Des données probantes récentes ont mis en lumière une atteinte de diverses voies biochimiques chez les patients susceptibles à l'HM en l'absence d'anesthésiques. Nous avons émis l'hypothèse que les différences cliniques entre les individus susceptibles à l'HM et des témoins se refléteraient dans des différences mesurables de métabolites myoplasmiques. MéTHODE : Nous avons réalisé un profilage métabolomique d'échantillons de muscles squelettiques provenant de personnes négatives à l'HM (témoins) et de patients susceptibles à l'HM subissant une biopsie musculaire dans le but de poser un diagnostic de susceptibilité à l'HM. Les métabolites cellulaires ont été extraits de 33 échantillons de muscles humains frais et de 87 échantillons congelés à l'aide d'une microextraction en phase solide et des plateformes de profilage biochimique non ciblées Metabolon®, respectivement. La chromatographie en phase liquide à haute performance et la spectrométrie de masse à haute résolution ont été utilisées pour l'identification et la validation des métabolites, puis suivies d'une analyse des différences dans les métabolites entre les groupes susceptibles à l'HM et les groupes négatifs à l'HM. RéSULTATS : Des différences significatives ont été observées entre les groupes susceptibles à l'HM et les groupes témoins dans les métabolites issus de diverses voies (P : de 0,009 à < 0,001). Ces différences comprenaient l'accumulation d'acylcarnitines à longue chaîne, de diacylglycérols, de phosphoénolpyruvate, de métabolites de la voie d'histidine, de lysophosphatidylcholine, de marqueurs de stress oxydatif, et de phosphoinositols, aussi bien que des taux réduits de monoacylglycérols. Les résultats des deux plateformes analytiques concordaient. CONCLUSION : Cette étude métabolomique indique un changement de l'utilisation des glucides vers les lipides pour la production d'énergie chez les personnes susceptibles à l'HM. Ce changement pourrait entraîner une inefficacité de la bêta-oxydation, ainsi qu'une augmentation du renouvellement des protéines musculaires, du stress oxydatif, et/ou des taux de lysophosphatidylcholine.

Personalized Ventilation to Multiple Patients Using a Single Ventilator: Description and Proof of Concept.

OBJECTIVES: To design and test a ventilator circuit that can be used for ventilation of two or more patients with a single ventilator, while allowing individualization of tidal volume, fractional concentration of oxygen, and positive end-expiratory pressure to each patient, irrespective of the other patient's respiratory system mechanics. DESIGN: Description and proof of concept studies. SETTINGS: Respiratory therapy laboratory. SUBJECTS: Ventilation of mechanical test lungs. INTERVENTIONS: Following a previously advocated design, we used components readily available in our hospital to assemble two "bag-in-a-box" breathing circuits. Each patient circuit consisted of a flexible bag in a rigid container connected via one-way valve to a test lung, along with an inline positive end-expiratory pressure valve, connected to the ventilator's expiratory limb. Compressed gas fills the bags during "patient" exhalation. During inspiration, gas from the ventilator, in pressure control mode, enters the containers and displaces gas from the bags to the test lungs. We varied tidal volume, "respiratory system" compliance, and positive end-expiratory pressure in one lung and observed the effect on the tidal volume of the other. MEASUREMENTS AND MAIN RESULTS: We were able to obtain different tidal volume, dynamic driving pressure, and positive end-expiratory pressure in the two lungs under widely different compliances in both lungs. Complete obstruction, or disconnection at the circuit connection to one test lung, had minimal effect (< 5% on average) on the ventilation to the co-ventilated lung. CONCLUSIONS: A secondary circuit "bag-in-the-box" system enables individualized ventilation of two lungs overcoming many of the concerns of ventilating more than one patient with a single ventilator.

Recent advances in nonoperating room anesthesia for cardiac procedures.

PURPOSE OF REVIEW: The number of complex procedures performed in the cardiac catheterization laboratory (CCL) is rapidly increasing. Because of their complexity, they frequently require the assistance of an anesthesiologist. The CCL is primarily designed to facilitate a percutaneous cardiac intervention; therefore, it might be a challenging workplace for an anesthesiologist. The aim of this review is to briefly present tasks and challenges of providing anesthesia in the CCL and to provide a concise description of common cardiac procedures performed there. RECENT FINDINGS: Recent literature indicates that many complicated cardiac procedures can be performed in CCL under monitored anesthesia care. At the same time several of them (e.g. transcatheter aortic valve replacement) are quickly becoming a viable alternative for surgical valve replacement. The most recent expansion of CCL procedures is related to rapidly growing population of grown-ups with congenital heart disease. All aforementioned developments present new challenges to an anesthesiologist. SUMMARY: New and fast development of percutaneous cardiac interventions has created a new working place for the anesthesiologist - the CCL. Our expertise in complex cardiac pathophysiology allows conduct of complicated procedures outside of the operating theater. For the same reasons, there is ongoing discussion whether anesthesia support in CCL should be provided by a general or cardiac anesthesiologist.

Intubation outside of the operating room: new challenges and opportunities in COVID-19 era.

PURPOSE OF REVIEW: Airway management in patients outside the operating room is associated with increased difficulties and risks, and the setting of the COVID-19 global pandemic adds another layer of complexity. Therefore, endotracheal intubation (ETT) of a patient who is presumptive COVID-19 or COVID-19 positive presents an additional challenge to an anesthesiologist. The aim of this review is to summarize the important principles of airway management outside of the operating room during the COVID-19 pandemic. RECENT FINDINGS: Several professional societies have formulated guidelines on airway management COVID-19 suspect and proven patients. Additionally, anesthesiologists working in hospitals treating many infected patients have developed specialized teams responsible for airway management outside the operating room. These documents and protocols focus on the importance of wearing personal protective equipment and the skills of the providers responsible for securing the airway. Staff safety is always a priority when performing ETT outside operating room. SUMMARY: The COVID-19 pandemic redefined the management of patients requiring aerosol generating procedures (droplet and airborne precautions). ETT is one of them and anesthesiologists are experts in performing airway management. Although the operating room is a highly controlled environment, airway management outside of this setting is not always the easiest task.

Review of the Transitional Pain Service as a method of postoperative opioid weaning and a service aimed at minimizing the risk of chronic post-surgical pain.

Opioid use and prescribing have become a subject of increasing focus and scrutiny. The ongoing "opioid epidemic" in North America has further increased interest in this area. In patients presenting for surgery, the prescribing of opioids during and following admission to hospital is commonplace and has been identified as a potential contributor to the growing opioid problem in North America. This review aims to present the timeline of the "opioid epidemic" as well as to introduce the concept of a "Transitional Pain Service". The Transitional Pain Service is a multidisciplinary service originating at Toronto General Hospital that employs a multi-faceted approach to monitoring opioid use after discharge from surgery, and aims to safely wean patients from opioids while maintaining effective pain management. This approach and its results will be discussed in this review.

The opioid crisis in North America: facts and future lessons for Europe.

Over the past two decades, opioid-related hospitalizations and deaths in North America have reached the level of a public health emergency. Initially, the epidemic of opioid misuse was largely driven by pharmaceutical companies and initiated by their spread of misinformation, which led physicians to engage in overzealous prescribing behaviour. This was followed by significant harms as deaths related to overdoses on prescription and illicit opioids rose steadily throughout the 1990s and early 2000s. This review examines the historical context of the opioid crisis in the United States and Canada, the role of physicians, the contributions of the pharmaceutical industry and the evolution of the epidemic in response to the introduction of highly potent synthetic opioids now recognized as the main culprits in opioid overdose and death. This article further explores the evidence surrounding the effectiveness of various treatment strategies and harm-reduction interventions designed to curtail the morbidity and mortality associated with opioid use. Finally, the magnitude of the opioid epidemic in North America is compared to that in European countries. This paper describes the differences in North American and European experiences with opioid overdose and the evidence-based approaches that can be implemented to reduce the mortality and morbidity linked to opioids while simultaneously ensuring adequate pain control for patients.

Current Evidence and Future Directions of Tranexamic Acid Use, Efficacy, and Dosing for Major Surgical Procedures.

Tranexamic acid reduces blood loss and transfusion requirements with no significant thrombotic adverse effects. Postoperative seizures have been seen in cardiac surgical patients in association with patient (advanced age, underlying neurologic disease, chronic kidney disease); surgical (open cardiac procedures, long bypass times); and drug (high tranexamic acid dose) risk factors. Tranexamic acid dosing regimens should be decreased in patients with chronic kidney dysfunction secondary to reduced clearance and drug accumulation. Optimal dosing for cardiac surgical patients has been recommended. Additional research is required to determine dosing regimens in major noncardiac surgery and plasma concentration levels associated with inducing seizures.

Intraoperative and Early Postoperative Management of Heart Transplantation: Anesthetic Implications.

The gold standard treatment for end-stage heart failure, with 50% mortality within 5 years of diagnosis, is considered heart transplantation. Despite the improvements in immunosuppression, the period of highest mortality risk in the heart transplantation population is during the first year post-transplantation, with primary graft dysfunction being the leading cause of mortality. After adequate preoperative assessment of the recipient, including patients on mechanical support, the intraoperative care of heart transplantation patients requires extensive monitoring followed by proficient management of anesthesia induction and maintenance, ventilation, and fluid therapy. The focus on weaning from cardiopulmonary bypass should be on preventing right ventricular failure and high pulmonary vascular resistances, with protocolized blood conservation strategies and transfusion protocols. The early postoperative care of a heart transplantation patient is focused on the post-cardiopulmonary bypass and transplantation status, with particular attention to the presence of primary graft dysfunction, right ventricular performance, pulmonary pressures, and vasoplegia. The aim is early extubation, inotropic and chronotropic support weaning, and chest tube removal to facilitate discharge of the patient from the intensive care unit. The increased complexity of heart transplantation recipients, including the incremental use of pre- transplantation mechanical circulatory support and extended criteria donor hearts, requires extensive and sophisticated preparation of the cardiac anesthesiologist. This article aims to provide an overview of the intraoperative and early postoperative anesthesia management of heart transplantation patients.

Solid phase microextraction coupled to mass spectrometry via a microfluidic open interface for rapid therapeutic drug monitoring.

Tranexamic acid (TXA) is an antifibrinolytic used during cardiac surgery that presents high inter-patient variability. High plasma concentrations have been associated with post-operative seizures. Due to the difficulties with maintaining acceptable concentrations of TXA during surgery, implementation of a point-of-care strategy for testing TXA plasma concentration would allow for close monitoring of its concentration during administration. This would facilitate timely corrections to the dosing schedule, and in effect tailor treatment for individual patient needs. In this work, a method for the rapid monitoring of TXA from plasma samples was subsequently carried out via biocompatible solid-phase microextraction (Bio-SPME) coupled directly to tandem mass spectrometry via a microfluidic open interface (MOI). MOI operates under the concept of a flow-isolated desorption volume and was designed with aims to directly hyphenate Bio-SPME to different detection and ionization systems. In addition, it allows the desorption of Bio-SPME fibers in small volumes while it concurrently continues feeding the ESI with a constant flow to minimize cross-talking and instabilities. The methodology was used to monitor six patients with varying degrees of renal dysfunction, at different time points during cardiac surgery. MOI proves to be a reliable and feasible tool for rapid therapeutic drug monitoring. Affording total times of analysis as low as 30 seconds per sample in its high throughput mode configuration while the single sample turn-around time was 15 minutes, including sample preparation. In addition, cross-validation against a standard thin film solid phase microextraction using liquid chromatography coupled to tandem mass spectrometry (TFME-LC-MS/MS) method was performed. Bland-Altman analysis was used to cross-validate the results obtained by the two methods. Data analysis demonstrated that 92% of the compared data pairs (n = 63) were distributed within the acceptable range. The data was also validated by the Passing Bablok regression, demonstrating good statistical agreement between these two methods. Finally, the currently presented method offers comparable results to the conventional liquid chromatography with acceptable RSDs, while only necessitating a fraction of the time. In this way, TXA concentration in plasma can be monitored in a close to real time throughput during surgery.

Predictor parameters of liver viability during porcine normothermic ex situ liver perfusion in a model of liver transplantation with marginal grafts.

Normothermic ex situ liver perfusion (NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters (biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart-beating donors (HBD), and from donors with 30 minutes (donation after cardiac death [DCD]30'), 70 minutes (DCD70'), and 120 minutes (DCD120') of warm ischemia were studied. The HBD, DCD30', and DCD70'-groups had 100% survival. In contrast, 70% developed primary nonfunction (PNF) and died in the DCD120'-group. Hepatocellular function during NEsLP showed low lactate (≤1.1 mmol/L) in all the groups except the DCD120'-group (>2 mmol/L) at 4 hours of perfusion (P = .04). The fold-urea increase was significantly lower in the DCD120'-group (≤0.4) compared to the other groups (≥0.65) (P = .01). As for cholangiocyte function, bile/perfusate glucose ratio was significantly lower (<0.6) in all the groups except the DCD120'-group (≥0.9) after 3 hours of perfusion (<0.01). Bile/perfusate Na+ ratio was significantly higher (≥1.2) after 3 hours of perfusion in all the groups except for the DCD120'-group (≤1) (P < .01). Three hours after transplantation, the DCD120'-group had a significantly higher international normalized ratio (>5) compared to the rest of the groups (≤1.9) (P = .02). Rocuronium levels were higher at all the time-points in the animals that developed PNF during NEsLP and after transplantation. This study demonstrates that biomarkers and markers of hepatocellular and cholangiocyte function during NEsLP correlate with the degree of ischemic injury and posttransplant function.

Comparison of propofol-based versus volatile-based anaesthesia and postoperative sedation in cardiac surgical patients: a prospective, randomized, study.

BACKGROUND: Clinical trials have shown conflicting results regarding the use of volatile anaesthesia before or after an ischaemic insult in cardiac surgical patients and its effect on myocardial injury. This may be attributable to the failure of continuing volatile agents into the early postoperative period. We hypothesised that combined volatilebased anaesthesia and postoperative sedation would decrease the extent of myocardial injury after coronary artery bypass grafting (CABG) when compared with an intravenous, propofol-based approach. This study aimed to assess the feasibility of the perioperative protocol and investigate whether volatile anaesthesia provides cardioprotection in patients undergoing CABG. METHODS: Randomized, controlled trial enrolling 157 patients with preserved left ventricular function scheduled for elective or urgent on-pump CABG. Patients received either volatile- or propofol-based anaesthesia and postoperative sedation. Volatile sedation in the ICU was provided with the use of the AnaConDa® device (Sedana Medical, Uppsala, Sweden). The primary outcome was myocardial injury measured by serial troponin measurement at the beginning of surgery, 2, 4 and 12-16 h after ICU admission. The secondary outcome was cardiac performance expressed as cardiac index (CI) and the need for inotropic and vasopressor drug support. The peak postoperative troponin level was defined as the highest level at any time in the first 16 h after surgery. RESULTS: 127 patients completed the study protocol, 60 patients in the volatile group and 67 patients in the propofol group. Troponin levels were similar between groups at all of the measured time points. There were no differences in cardiac index or vasoactive drug support except for the immediate post- cardiopulmonary bypass (CPB) period when patients in the volatile group had low systemic vascular resistance, high CI and required more vasopressors. There was no difference in postoperative kidney function, intensive care unit discharge or hospital discharge time. CONCLUSIONS: The use of volatile-based anaesthesia and postoperative sedation did not confer any cardioprotection compared with propofol-based anaesthesia and sedation in patients who had good left ventricular function and were undergoing CABG.