OBJECTIVES:To optimize protamine titration for heparin antagonization after weaning from cardiopulmonary bypass (CPB). DESIGN:A prospective, observational trial. SETTING:Single-center, non-university teaching hospital. PARTICIPANTS:Forty patients presenting for elective on-pump coronary artery bypass grafting with or without single valve surgery. INTERVENTIONS:At the end of CPB, the residual amount of heparin in the patient was estimated using a Bull-curve. The total protamine dose was calculated as 1 unit of protamine for 1 unit of heparin. Protamine was administered as 5 aliquots containing 20% of the total protamine dose each, with 2-min intervals. MEASUREMENTS AND MAIN RESULTS:Activated Clotting Time (ACT) values were measured 2 min after administration of each aliquot. ROTEM(®)-analysis was performed after the full dose of protamine had been administered. After 60% of the total protamine dose had been administered, ACT values were normalized in 86.5% of patients. After the complete dose of protamine had been administered, 61.1% of patients displayed signs of protamine overdose on ROTEM(®)-analysis. CONCLUSIONS:In patients who present for on-pump coronary artery bypass grafting with or without single valve surgery, a 0.6-to-1 ratio of protamine-to-heparin to antagonize heparin may be sufficient and beneficial for patients.

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59-74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51, 789-808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.

Intubation in patients with cervical spine injury with neurological deficits needing urgent surgery mandates and careful airway management. Video laryngoscopy-guided intubation in an awake patient can be a useful option as the patient can himself participate in the airway management. The patient can follow commands, protrude the tongue, and indicate discomfort or pain during inadvertent or excessive head extension. We wish to report our experience of 10 patients with documented neurological compromise needing urgent surgery after cervical spine trauma where we used the King Vision video laryngoscope for awake tracheal intubation. Nine out of 10 patients were successfully intubated with the King Vision but we could not intubate one patient for which fibreoptic bronchoscope-guided intubation was performed. Three patient needed gum elastic bougie assistance for intubation. The mean time for intubation ranged from 1.2 minutes to 2.6 minutes. Pain and discomfort during the intubation attempt were noted to be acceptable.

Residual neuromuscular block (NMB) may persist in the post-anaesthesia care unit (PACU). Studies in our department found that our incidence of postoperative residual NMB was approximately 40% in 2006 and 14% in 2012. We would like to report the results of a follow-up study of residual NMB in our department in 2018. The primary objective of this study was to evaluate the incidence of residual NMB, defined by a train-of-four ratio (TOFR)< 0.9 on PACU arrival. This observational study involved patients undergoing different types of elective surgery that required general anaesthesia with neuromuscular blocking agents (NMBAs). The anaesthetic technique and the management of NMB in the operating room were conducted at the discretion of the attending anaesthetist and were performed in accordance with our standard clinical practice and with reference to published practice guidelines for the intraoperative management of NMB. After signed informed consent, 587 patients were prospectively and successively enrolled in our study. The study was approved by the Ethics Committee of the Onze-Lieve-Vrouw Ziekenhuis, Aalst, Belgium (Approval 2017/077, Chairperson Dr A Leloup) on 6 October 2017 and is registered at ClinicalTrials.gov (ID: NCT03665805). On arrival in the PACU, a nurse trained in TOFR monitoring (TOFscan, iDMed, Marseille, France) recorded the acceleromyographic responses of the adductor pollicis muscle (as the TOFR) on TOF stimulation of the ulnar nerve. The stimulus current was set at 30 mA for the purpose of tolerance. Two consecutive TOF measurements (separated by 15 seconds) were obtained, and the average of the two values was registered. We recorded whether neuromuscular transmission (NMT) monitoring was used before extubation of the trachea in the operating room and whether extubation in the operating room was preceded by pharmacological reversal with either neostigmine or sugammadex. Patients’ characteristics and perioperative data, as well as the management of NMB, and the incidence of residual NMB were retrieved from the 2012 results, and the same variables were collected for the 2018 study. We compared the variables between the two periods using Mann–Whitney tests for continuous variables and chi-square tests for categorical variables. In addition, we divided the 2018 TOFR results into six subgroups: a) patients not monitored with NMT and not reversed with reversal agents (n1⁄4 112); b) patients who had no NMT monitoring but had reversal with neostigmine (n1⁄4 33); c) patients monitored but not reversed (n1⁄4 181); d) patients monitored and reversed with neostigmine (n1⁄4 181); e) patients monitored and reversed with sugammadex (n1⁄4 75); and f) patients monitored and reversed with both neostigmine and sugammadex (n1⁄4 5). We then calculated how many patients in each subgroup had a TOFR between 0.7 and 0.9 and how many had a TOFR< 0.7. Table 1 shows the characteristics of the patients and their intraoperative NMB monitoring, reversal management and the incidence of residual NMB for the 2012 and the 2018 studies. Both the use of neuromuscular monitoring and the proportion of patients who had NMB reversed pharmacologically increased between 2012 and 2018. Surprisingly, however, there was no significant decrease in the proportion of patients with residual NMB. The incidence of a TOFR< 0.9 remained at 14% for both periods. Moreover, despite literature

Purpose of Review The purpose of this review is to assess how residual neuromuscular block impacts postoperative pulmonary complications and whether we can modify the risk by improving certain aspects in daily clinical care. Recent findings Postoperative respiratory impairment may be due to various causes, such as age, surgery type, comorbidity, smoking, preoperative anemia, and general anesthesia. However, increasing evidence suggests that residual neuromuscular block is an important risk factor for postoperative pulmonary complications and may affect the outcome. Conflicting data from some recent reports show that the use of quantitative neuromuscular monitoring alone does not preclude residual neuromuscular block and that improvements in the interpretation of neuromuscular monitoring may be required. Pulmonary complications seem to be reduced for train-of-four ratios > 0.95 before tracheal extubation compared with > 0.9. Summary This review stresses the need for appropriate management of neuromuscular block in the prevention of postoperative pulmonary complications but acknowledges that the causes are multifactorial.

Editor, Muscle weakness is a common finding in ICU patients and occurs especially when patients are mechanically ventilated for more than 24 h.1,2 Few data are available on the monitoring of neuromuscular transmission (NMT) in the ICU, as quantitative NMT monitoring may fail, as many factors can interfere with its accuracy.3 Moreover, there might be a difference in accuracy and performance of the train-of-four ratio (TOFR) due to pre-existing TOF fade in association with acquired muscle weakness or severe diseases of the peripheral nervous system.4 We therefore proposed to investigate and compare the optimal neuromuscular monitoring techniques (acceleromyography vs. electromyography) and the optimal muscle monitoring site (peripheral-adductor pollicis or abductor digiti minimi vs. central-corrugator supercilii muscles) in ICU patients who require prolonged mechanical ventilation. This prospective observational feasibility study was approved by the ethical committee of the Onze-Lieve-Vrouw Ziekenhuis, Aalst, Belgium (Approval Number: 2018/091, Chairperson Dr A. Leloup) on 17 December 2018 and was registered with ClinicalTrials.gov (ref: NCT03778749). Written informed consent was obtained from each patient's healthcare proxy. Twelve ICU patients, mechanically ventilated for at least 24 h, and who were expected to require mechanical ventilation for at least 72 additional hours, were recruited consecutively. None of the patients had received neuromuscular blocking agents (NMBAs) in the preceding 24 h. In the first eight appropriately sedated patients, we recorded the TOFR at the corrugator supercilii muscle [measured with the eye probe of the TofScan accelerometer (iDMed, Marseille, France)], at the adductor pollicis [measured with the Stimpod (Xavant Technology Ltd, Pretoria, South Africa) accelerometer], and at the adductor pollicis [using the electromyography-based TetraGraph (Senzime AB, Uppsala, Sweden) NMT monitor]. The current intensity for all neurostimulation was 30 mA; the stimulation pattern of both ulnar and facial nerves was TOF delivered every 1 min, and the mean of three consecutive measurements was calculated as the TOFR. Patients were tested every 24 h, once per day, at the same time, for 72 consecutive hours. In another four patients, we performed a TOFR measurement with the electromyography-based TetraGraph at two muscle sites: the corrugator supercilii (eyebrow) and at the abductor digiti minimi muscle of the hand. In this small group of mechanically ventilated and sedated ICU patients, TOFR values varied considerably in each individual patient at the different monitoring sites, as well as between patients at the different monitoring sites, and with the different monitoring devices (Tables 1 and 2). We could not demonstrate TOFR reproducibility with the three monitors and, although we were able to get more recordings after acceleromyography of the corrugator supercilii, this was not confirmed by electromyography of the muscle.Table 1: Electromyographic and acceleromyographic neuromuscular monitoring recordings (mean train-of-four ratio) with 30 mA current at different muscle sites in eight ventilated ICU patientsTable 2: Electromyographic neuromuscular monitoring recordings (mean train-of-four ratio) at different muscle sites in four ventilated ICU patientsICU-acquired neuropathy and oedema could be responsible for the poor response to peripheral neurostimulation. Moreover, the typical ICU setting that includes periods of weaning and increasing/decreasing sedation may have been responsible for technical and interpretative issues during the study, as spontaneous muscle movement in partly sedated patients and the high likelihood of direct facial muscle stimulation may have been confounding the recordings. In addition, the neurostimulation current intensity of 30 mA likely was insufficient to achieve meaningful muscle responses in critically ill patients due to peripheral tissue oedema. In conclusion, this study did not establish the optimal NMT monitor or current intensity for use in the ICU setting: neither the newer generation of quantitative electromyographic and acceleromyographic monitors, nor using sites other than the adductor pollicis increased the success rate of NMT monitoring in mechanically ventilated ICU patients. The clinical usefulness of the information provided was thus limited. Future investigations should focus on optimising the total charge (current intensity x pulse duration) delivered peripherally in order to obtain clinically useful neuromuscular function information for the benefits of ICU patients.

After cardiac surgery, a certain degree of myocardial injury is common. The arbitrarily proposed biomarker cut-off point in the Third Universal Definition for diagnosing coronary artery bypass grafting (CABG)–related perioperative myocardial infarction (PMI) is controversial and unvalidated for non-CABG surgery. Minimally invasive cardiac surgery is often thought to be associated with less myocardial damage compared to conventional surgical approaches. We conducted a real-life prospective study with serial sampling of high-sensitivity cardiac troponin T (hs-cTnT) in patients undergoing conventional and minimally invasive cardiac surgery. Four different types of cardiac surgery were performed in 400 patients (February 2014–January 2015): CABG, aortic valve replacement, minimally invasive mitral/tricuspid valve surgery through the HeartPort (HP) technique and combined CABG/valve surgery. Each group was further subdivided for comparison between the different surgical techniques. Blood samples were collected consecutively at intensive care unit (ICU) admission and 3, 6, 9, 12, 18, 24 and 48 h thereafter. The hs-cTnT values by peak timepoint differed significantly depending on the surgical approach. The overall peak timepoint for hs-cTnT occurred 6 h after ICU admission. The combined surgery and multiple-valve HP groups had the highest values (medians of 1067.5 (744.9–1455) ng/L and 1166 (743.7–2470) ng/L, respectively). The peak hs-cTnT values for patients developing PMI showed high variability. Differentiation between cardiac surgery–related necrosis and PMI remains challenging. This study emphasizes the importance of a clinically reliable biomarker cut-off value in addition to electrocardiography and echocardiography to optimize PMI diagnosis.

Background : The incidence of postoperative residual weakness remains unacceptably high and essentially unchanged over decades. It is puzzling why anesthesiologists are resistant to accept the concepts of safe management of neuromuscular blockade and reversal. It appears that pervasive misconceptions regarding appropriate implementation of neuromuscular blockade monitoring and management continue to be a substantial obstacle in addressing this issue. Methods : We conducted a 10-question survey composed of true/false options to determine the respondents' knowledge regarding neuromuscular blockade management. Surveys were made available during an unannounced 90 minute period of a national anesthesiology conference in Belgium. Participants were also asked to rate their confidence in their responses. Results : One hundred and fifty-seven anesthesiologists (69 certified anesthesiologists and 88 anesthesiologists- in-training) completed the 10-question survey. Respondents were correct 72% of the time, yet rated their mean confidence significantly higher as 80%. Conclusions : The surveyed anesthesia providers conveyed overconfidence in their understanding of neuromuscular blockade management. Such misconceptions represent a substantial challenge to improving the standards of neuromuscular blockade management throughout the anesthesia community.

The purpose of this review is to assess how sugammadex impacts postoperative residual curarization using appropriate doses based on neuromuscular transmission monitoring and whether the advantages of sugammadex versus neostigmine outweigh its higher cost.

This pilot study in rats demonstrated an increased relative contribution of chest wall expansion after neostigmine compared with sugammadex or saline. This smaller relative contribution of diaphragm movement may be explained by a neostigmine-induced decrease in phrenic nerve activity or by remaining occupied acetylcholine receptors after neostigmine.

Reductions in diaphragm activity are associated with the postoperative development of atelectasis. Neostigmine reversal is also associated with increased atelectasis. We assessed the effects of neostigmine, sugammadex, and spontaneous reversal on regional lung ventilation and airway flow.Six Sprague-Dawley rats were paralysed with rocuronium and mechanically ventilated until recovery of the train-of-four ratio to 0.5. We administered neostigmine (0.06mg.kg-1), sugammadex (15mg.kg-1), or saline (n=2 per group). Computed tomography scans were obtained during the breathing cycle. Three-dimensional models of lung lobes were generated using functional respiratory imaging technology, and lobar volumes were calculated during the breathing cycle. The diaphragmatic surface was segmented for the end-expiratory and end-inspiratory scans. The total change in volume was reported by the lung volume change from the end-expiratory scan to the end-inspiratory scan. Chest wall movement was defined as the lung volume change minus the volume change that resulted from diaphragm excursion.The two rats that received neostigmine exhibited a smaller relative contribution of diaphragm movement to the total change in lung volume compared with the two rats that received sugammadex or saline (chest wall contribution (%): 26.69 and 25.55 for neostigmine; -2.77 and 15.98 for sugammadex; 18.82 and 10.30 for saline).This pilot study in rats demonstrated an increased relative contribution of chest wall expansion after neostigmine compared with sugammadex or saline. This smaller relative contribution of diaphragm movement may be explained by a neostigmine-induced decrease in phrenic nerve activity or by remaining occupied acetylcholine receptors after neostigmine.

Reductions in diaphragm activity are associated with the postoperative development of atelectasis. Neostigmine reversal is also associated with increased atelectasis. We assessed the effects of neostigmine, sugammadex, and spontaneous reversal on regional lung ventilation and airway flow. Six Sprague–Dawley rats were paralysed with rocuronium and mechanically ventilated until recovery of the train-of-four ratio to 0.5. We administered neostigmine (0.06 mg.kg−1), sugammadex (15 mg.kg−1), or saline (n = 2 per group). Computed tomography scans were obtained during the breathing cycle. Three-dimensional models of lung lobes were generated using functional respiratory imaging technology, and lobar volumes were calculated during the breathing cycle. The diaphragmatic surface was segmented for the end-expiratory and end-inspiratory scans. The total change in volume was reported by the lung volume change from the end-expiratory scan to the end-inspiratory scan. Chest wall movement was defined as the lung volume change minus the volume change that resulted from diaphragm excursion. The two rats that received neostigmine exhibited a smaller relative contribution of diaphragm movement to the total change in lung volume compared with the two rats that received sugammadex or saline (chest wall contribution (%): 26.69 and 25.55 for neostigmine; −2.77 and 15.98 for sugammadex; 18.82 and 10.30 for saline). This pilot study in rats demonstrated an increased relative contribution of chest wall expansion after neostigmine compared with sugammadex or saline. This smaller relative contribution of diaphragm movement may be explained by a neostigmine-induced decrease in phrenic nerve activity or by remaining occupied acetylcholine receptors after neostigmine. As reduções da atividade do diafragma estão associadas ao desenvolvimento de atelectasia no período pós-operatório. A reversão com neostigmina também está associada ao aumento de atelectasia. Avaliamos os efeitos de neostigmina, sugamadex e da reversão espontânea sobre a ventilação pulmonar regional e fluxo aéreo. Seis ratos Sprague-Dawley foram paralisados com rocurônio e mecanicamente ventilados até a recuperação da sequência de quatro estímulos atingir relação 0,5. Administramos neostigmina (0,06 mg.kg−1), sugamadex (15 mg.kg−1) ou solução salina (n = 2 por grupo). As tomografias foram realizadas durante o ciclo respiratório. Modelos tridimensionais dos lobos pulmonares foram gerados usando a tecnologia de imagem funcional respiratória e os volumes lobares foram calculados durante o ciclo respiratório. A superfície diafragmática foi segmentada para as varreduras expiratória final e inspiratória final. A alteração total no volume foi relatada pela alteração do volume pulmonar da varredura expiratória final para a varredura inspiratória final. O movimento da parede torácica foi definido como a variação do volume pulmonar menos a alteração no volume resultante da excursão do diafragma. Os dois ratos que receberam neostigmina apresentaram uma contribuição relativa menor do movimento do diafragma para a alteração total do volume pulmonar em comparação com os dois ratos que receberam sugamadex ou solução salina (contribuição da parede torácica (%): 26,69 e 25,55 para neostigmina; -2,77 e 15.98 para sugamadex; 18,82 e 10,30 para solução salina). Este estudo piloto com ratos demonstrou uma contribuição relativa aumentada de expansão da parede torácica após neostigmine em comparação com sugamadex ou solução salina. Essa contribuição relativa menor de movimento do diafragma pode ser explicada por uma redução induzida por neostigmina na atividade do nervo frênico ou por receptores de acetilcolina permanecerem ocupados após a administração de neostigmina.

BACKGROUND Electromyographic activity of the diaphragm (EMGdi) during weaning from mechanical ventilation is increased after sugammadex compared with neostigmine.OBJECTIVE To determine the effect of neostigmine on EMGdi and surface EMG (sEMG) of the intercostal muscles during antagonism of rocuronium block with neostigmine, sugammadex and neostigmine followed by sugammadex.DESIGN Randomised, controlled, double-blind study.SETTING Intensive care research unit.PARTICIPANTS Eighteen male volunteers.INTERVENTIONS A transoesophageal EMGdi recorder was inserted into three groups of six anaesthetised study participants, and sEMG was recorded on their intercostal muscles. To reverse rocuronium, volunteers received 50mg kg(-1) neostigmine, 2mg kg(-1) sugammadex or 50mg kg(-1) neostigmine, followed 3 min later by 2mg kg(-1) sugammadex.MAIN OUTCOME MEASURES We examined the EMGdi and sEMG at the intercostal muscles during recovery enhanced by neostigmine or sugammadex or neostigmine-sugammadex as primary outcomes. Secondary objectives were the tidal volume, PaO2 recorded between the onset of spontaneous breathing and extubation of the trachea and SpO(2) during and after anaesthesia.RESULTS During weaning, median peak EMGdi was 0.76 (95% confidence interval: 1.20 to 1.80) mV in the neostigmine group, 1.00 (1.23 to 1.82) mV in the sugammadex group and 0.70 (0.91 to 1.21) mV in the neostigminesugammadex group (P<0.0001 with EMGdi increased after sugammadex vs. neostigmine and neostigmine-sugammadex). The median peak intercostal sEMG for the neostigmine group was 0.39 (0.65 to 0.93) mV vs. 0.77 (1.15 to 1.51) mV in the sugammadex group and 0.82 (1.28 to 2.38) mV in the neostigmine-sugammadex group (P<0.0001 with sEMG higher after sugammadex and after neostigmine-sugammadex vs. neostigmine).CONCLUSION EMGdi and sEMG on the intercostal muscles were increased after sugammadex alone compared with neostigmine. Adding sugammadex after neostigmine reduced the EMGdi compared with sugammadex alone. Unlike the diaphragm, intercostal EMG was preserved with neostigmine followed by sugammadex.

BACKGROUND:The use of neuromuscular blocking agents has been associated with severe postoperative respiratory morbidity. Complications can be attributed to inadequate reversal, and reversal agents may themselves have adverse effects. OBJECTIVE:To compare the electromyographic activity of the diaphragm (EMGdi) during recovery from neuromuscular blockade using neostigmine and sugammadex. The hypothesis was that there would be better neuromuscular coupling of the diaphragm when sugammadex was used. DESIGN:A randomised, controlled, parallel-group, single-centre, double-blinded study. SETTING:District general hospital in Belgium. PARTICIPANTS:Twelve healthy male volunteers. INTERVENTIONS:Individuals were anaesthetised with propofol and remifentanil. After rocuronium 0.6 mg kg, a transoesophageal electromyography (EMG) recorder was inserted. For reversal of neuromuscular blockade, volunteers received sugammadex 2 mg kg (n = 6) or neostigmine 70 μg kg (n = 6). MAIN OUTCOME MEASURES:EMGdi, airway pressure and flow were continuously measured during weaning from the ventilator until tracheal extubation. Arterial blood gas samples were obtained for PaO2 and PaCO2 analysis at the first spontaneous breathing attempt and after tracheal extubation. RESULTS:During weaning, 560 breaths were retained for analysis. The median (95% CI) peak EMGdi was 1.1 (0.9 to 1.5) μV in the neostigmine group and 1.6 (1.3 to 1.9) μV in the sugammadex group (P < 0.001). Individuals in the neostigmine group had 125 of 228 (55%) breaths with associated EMGdi at least 1 μV vs. 220 of 332 (66%) breaths in the sugammadex group (P = 0.008). The median (95% CI) tidal volume was 287 (256 to 335) ml after neostigmine and 359 (313 to 398) ml after sugammadex (P = 0.013). The median (95% CI) PaO2 immediately after extubation was 30.5 (22.8 to 37.1) kPa after sugammadex vs. 20.7 (12.9 to 27.5) kPa after neostigmine (P = 0.03). CONCLUSION:EMGdi, tidal volume and PaO2 following tracheal extubation were increased after sugammadex compared with neostigmine, reflecting diaphragm-driven inspiration after sugammadex administration. Sugammadex may free more diaphragmatic acetylcholine receptors than neostigmine, which has an indirect effect. TRIAL REGISTRATION:EudraCT ref: 2013-002078-30.

Hs-cTn is the new standard cardiac biomarker for the diagnosis of myocardial necrosis. We conducted a prospective study to compare the course and values of the Hs-cTn and CK-MB after CABG and OPCAB. We also evaluated the relationship between values >10 × 99th percentile URL of CK-MB and Hs-cTn as a possible marker for perioperative myocardial infarction.

High-sensitive cardiac troponin (Hs-cTn) is the new standard cardiac biomarker for the diagnosis of myocardial necrosis [1].