Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision.

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.

Protamine titration to optimize heparin antagonization after cardiopulmonary bypass.

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.

Diaphragmatic and intercostal electromyographic activity during neostigmine, sugammadex and neostigmine-sugammadex-enhanced recovery after neuromuscular blockade: A randomised controlled volunteer study.

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 50 µg kg neostigmine, 2 mg kg sugammadex or 50 µg kg neostigmine, followed 3 min later by 2 mg kg 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 SpO2 during and after anaesthesia. RESULTS: During weaning, median peak EMGdi was 0.76 (95% confidence interval: 1.20 to 1.80) µV in the neostigmine group, 1.00 (1.23 to 1.82) µV in the sugammadex group and 0.70 (0.91 to 1.21) µV in the neostigmine-sugammadex 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) µV vs. 0.77 (1.15 to 1.51) µV in the sugammadex group and 0.82 (1.28 to 2.38) µV 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. TRIAL REGISTRATION: EudraCT: 2015-001278-16; ClinicalTrials.gov: NCT02403063.

Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers.

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.

Neuromuscular blockade: what was, is and will be.

Non-depolarizing neuromuscular blocking agents (NMBAs) produce neuromuscular blockade by competing with acetylcholine at the neuromuscular junction, whereas depolarizing NMBAs open receptor channels in a manner similar to that of acetylcholine. Problems with NMBAs include malignant hyperthermia caused by succinylcholine, anaphylaxis with the highest incidence for succinylcholine and rocuronium, and residual neuromuscular blockade. To reverse these blocks, anticholinesterases can act indirectly by increasing the amount of acetylcholine in the neuromuscular junction; sugammadex is the only selective relaxant binding agent (SRBA) in clinical use. At all levels of blockade, recovery after sugammadex is faster than after neostigmine. Sugammadex potentially also has some other advantages over neostigmine that are related to neostigmine's increase in the amount of acetylcholine and the necessity of co-administering anticholinergics. However, hypersensitivity reactions, including anaphylaxis, have occurred in some patients and healthy volunteers after sugammadex and remain an issue for the FDA. In the near future, we may see the emergence of new SRBAs and of easier-to-use technologies that can routinely monitor neuromuscular transmissions in daily practice. The nature of the effect of sugammadex on freeing nicotinic acetylcholine receptors located outside the neuromuscular junction from NMBAs is unknown. Moreover, it is uncertain whether the full removal of the competing antagonists (by SRBAs) at the neuromuscular junction impacts the efficiency of acetylcholine transmission. In a recent pilot study in healthy volunteers, we demonstrated increased electromyographic diaphragm activity after sugammadex, compared to neostigmine. Further research is needed to elucidate the role of NMBAs and their reversal agents in the central control of breathing, respiratory muscle activity, and respiratory outcomes.

Management of tight intraoperative glycemic control during off-pump coronary artery bypass surgery in diabetic and nondiabetic patients.

OBJECTIVES: To optimize intra- and postoperative insulin management in cardiac surgical patients. DESIGN: A prospective, randomized, open-label, single-center study. SETTING: A large nonuniversity hospital. PARTICIPANTS: Sixty diabetics and 60 nondiabetics undergoing off-pump cardiac bypass surgery. INTERVENTIONS: Intra- and postoperative tight glycemic control were achieved using different approaches with a modified insulin protocol. MEASUREMENTS AND MAIN RESULTS: Nondiabetics were divided randomly: in the ND-ind group (n = 30), insulin was started at induction according to preinduction blood glucose (BG) concentrations. In group ND >110 (n = 30), insulin was started when BG concentrations exceeded 110 mg/dL during surgery. Up to 85% of the ND >110 group started on insulin intraoperatively. Intraoperatively, the ND-ind group had more BG within target (80-110 mg/dL) (p = 0.002), less BG >130 mg/dL (p = 0.015), and more BG between 70 and 79 mg/dL (p = 0.002). In diabetics, BG concentration was checked every 30 (DM-30), n = 30) versus 60 minutes (DM-60, n = 30) to improve the protocol's performance. Intraoperatively, there were more BG concentrations within target (80-110 mg/dL) (p = 0.02) and less >130 mg/dL (p = 0.0002) in the DM-30 group. During surgery, the hyperglycemic index and the glycemic penalty index were lower in the ND-ind group (p < 0.05). Postoperatively, the mean BG concentrations, hyperglycemic index, and glycemic penalty index in diabetics and nondiabetics were comparable between groups (p < 0.05). In the overall 2,641 BG samples, the lowest BG concentration in the operating room was 71 and in the intensive care unit (ICU) it was 61 mg/dL. CONCLUSIONS: In diabetics and nondiabetics undergoing off-pump coronary artery bypass surgery, tight perioperative glycemic control is feasible and efficient, with minimal risks for hypo- and hyperglycemia. In nondiabetics, starting insulin therapy from induction onwards results in more measurements within target, without affecting the mean BG. In diabetics, decreasing the sampling interval from 60 to 30 minutes results in more measurements within target and in a mean blood glucose within target at ICU arrival.

Residual Neuromuscular Blockade and Postoperative Pulmonary Complications: What Does the Recent Evidence Demonstrate?

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.

Tight perioperative glucose control is associated with a reduction in renal impairment and renal failure in non-diabetic cardiac surgical patients.

INTRODUCTION: Acute renal failure after cardiac surgery increases in-hospital mortality. We evaluated the effect of intra- and postoperative tight control of blood glucose levels on renal function after cardiac surgery based on the Risk, Injury, Failure, Loss, and End-stage kidney failure (RIFLE) criteria, and on the need for acute postoperative dialysis. METHODS: We retrospectively analyzed two groups of consecutive patients undergoing cardiac surgery with cardiopulmonary bypass between August 2004 and June 2006. In the first group, no tight glycemic control was implemented (Control, n = 305). Insulin therapy was initiated at blood glucose levels > 150 mg/dL. In the group with tight glycemic control (Insulin, n = 745), intra- and postoperative blood glucose levels were targeted between 80 to 110 mg/dL, using the Aalst Glycemia Insulin Protocol. Postoperative renal impairment or failure was evaluated with the RIFLE score, based on serum creatinine, glomerular filtration rate and/or urinary output. We used the Cleveland Clinic Severity Score to compare the predicted vs observed incidence of acute postoperative dialysis between groups. RESULTS: Mean blood glucose levels in the Insulin group were lower compared to the Control group from rewarming on cardiopulmonary bypass onwards until ICU discharge (p < 0.0001). Median ICU stay was 2 days in both groups. In non-diabetics, strict perioperative blood glucose control was associated with a reduced incidence of renal impairment (p = 0.01) and failure (p = 0.02) scoring according to RIFLE criteria, as well as a reduced incidence of acute postoperative dialysis (from 3.9% in Control to 0.7% in Insulin; p < 0.01). The 30-day mortality was lower in the Insulin than in the Control group (1.2% vs 3.6%; p = 0.02), representing a 70% decrease in non-diabetics (p < 0.05) and 56.1% in diabetics (not significant). The observed overall incidence of acute postoperative dialysis was adequately predicted by the Cleveland Clinic Severity Score in the Control group (p = 0.6), but was lower than predicted in the Insulin group (1.2% vs 3%, p = 0.03). CONCLUSIONS: In non-diabetic patients, tight perioperative blood glucose control is associated with a significant reduction in postoperative renal impairment and failure after cardiac surgery according to the RIFLE criteria. In non-diabetics, tight blood glucose control was associated with a decreased need for postoperative dialysis, as well as 30-day mortality, despite of a relatively short ICU stay.

Dynamic tight glycemic control during and after cardiac surgery is effective, feasible, and safe.

BACKGROUND: Tight blood glucose control reduces mortality and morbidity in critically ill patients, but intraoperative glucose control during cardiac surgery is often difficult, and risks hypoglycemia. In this study, we evaluated the safety and efficacy of a nurse-driven insulin protocol (the Aalst Glycemia Insulin Protocol) for achieving a target glucose level of 80-110 mg/dL during cardiac surgery and in the intensive care unit (ICU). METHODS: We included 483 nondiabetics and 168 diabetics scheduled for cardiac surgery with cardiopulmonary bypass. To anticipate rapid perioperative changes in insulin requirement and/or sensitivity during surgery, we developed a dynamic algorithm presented in tabular form, with rows representing blood glucose ranges and columns representing insulin dosages based on the patients' insulin sensitivity. The algorithm adjusts insulin dosage based on blood glucose level and the projected insulin sensitivity (e.g., reduced sensitivity during cardiopulmonary bypass and normalizing sensitivity after surgery). RESULTS: A total of 18,893 blood glucose measurements were made during and after surgery. During surgery, the mean glucose level in nondiabetic patients was within targeted levels except during (112 +/- 17 mg/dL) and after rewarming (113 +/- 19 mg/dL) on cardiopulmonary bypass. In diabetics, blood glucose was decreased from 121 +/- 40 mg/dL at anesthesia induction to 112 +/- 26 mg/dL at the end of surgery (P < 0.05), with 52.9% of patients achieving the target. In the ICU, the mean glucose level was within targeted range at all time points, except for diabetics upon ICU arrival (113 +/- 24 mg/dL). Of all blood glucose measurements (operating room and ICU), 68.0% were within the target, with 0.12% of measurements in nondiabetics and 0.18% in diabetics below 60 mg/dL. Hypoglycemia < 50 mg/dL was avoided in all but four (0.6%) patients (40 mg/dL was the lowest observed value). CONCLUSIONS: The Aalst Glycemia Insulin Protocol is effective for maintaining tight perioperative blood glucose control during cardiac surgery with minimal risk of hypoglycemia.

Sugammadex: Appropriate Use in the Context of Budgetary Constraints.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: An accurate assessment of neuromuscular blockade with monitoring is necessary before selecting neostigmine versus sugammadex for reversal at the end of surgery to overcome incomplete neuromuscular recovery. The main advantages of sugammadex over neostigmine are its predictability and its ability to extend the range of blockade reversal. The cost of sugammadex is greater when higher doses of sugammadex are required for antagonism of deep block. Sugammadex probably has the potential to be cost-effective compared with neostigmine if its time savings are put to productive use in clinical practice. However, to date, the economic benefits of the drug are unknown. SUMMARY: With sugammadex, almost any degree of neuromuscular block can be antagonized within 2-3 min; neostigmine is the only reversal agent effective against benzylisoquinolines and can ideally be used for reversal of lower levels of residual paralysis. The performance of the more expensive sugammadex on improving patient outcomes may depend on several elements of clinical strategy.

Muscle relaxation does not influence venous oxygen saturation during cardiopulmonary bypass.

STUDY OBJECTIVE: To examine whether the omission of neuromuscular blocking drugs during cardiopulmonary bypass (CPB) is associated with increased anesthetic requirements, higher frequency of intraoperative movements, and lower venous oxygen saturation (SvO(2)). DESIGN: Prospective, randomized study. SETTING: Large community hospital. PATIENTS: 30 ASA physical status III and IV patients scheduled for cardiac surgery. INTERVENTIONS: Patients were randomized to one of two groups: group 1 (n = 15) received a 3xED(95) bolus dose of cisatracurium at induction and thereafter no more neuromuscular blocking drug; group 2 (n = 15) received a continuous infusion of cisatracurium during the entire procedure. INTERVENTIONS: Both groups received a standardized anesthetic with bispectral index-guided propofol target-controlled infusion and a remifentanil infusion steered by hemodynamic changes. Venous oxygen saturation was continuously determined during CPB. MEASUREMENTS AND MAIN RESULTS: Propofol consumption was 5.4 +/- 1.7 and 4.4 +/- 1.0 mg/(kg/h) in groups 1 and 2, respectively (P = 0.07). Remifentanil consumption was 0.15 +/- 0.05 and 0.17 +/- 0.05 mug/(kg/min) in groups 1 and 2, respectively (P = 0.19). In groups 1 and 2, no patient recalled any intraoperative phenomena; none moved or had diaphragmatic contractions. During CPB, SvO(2) was 81.3 +/- 3.2% (76%-85%) in group 1 and 80.6 +/- 3.1% (73%-85%) in group 2 (P = 0.53). CONCLUSIONS: Omitting the continuous administration of neuromuscular blocking drugs during CPB did not increase anesthetic requirements. No intraoperative movements occurred, nor was there decreased SvO(2).

Preinduction glycemia and body mass index are important predictors of perioperative insulin management in patients undergoing cardiac surgery.

STUDY OBJECTIVE: To investigate whether preinduction glucose is an important predictor for perioperative insulin management in patients undergoing cardiac surgery. DESIGN: Prospective cohort study. SETTING: Large community hospital. PATIENTS: 80 consecutive patients scheduled for cardiac surgery. INTERVENTIONS: Patients were subdivided into those with a preinduction blood glucose of 110 mg/dL or lower with or without history of diabetes (group 1) and those with a preinduction blood glucose of above 110 mg/dL with or without history of diabetes (group 2). In group 1, there were no known diabetics. In group 2, 31% (11/35) had diabetes (group 2DM), while 24/35 (69%) did not (group 2NDM). An insulin infusion was started intraoperatively and adjusted according to a strict protocol in order to maintain normoglycemia (80-110 mg/dL) until discharge from intensive care. MEASUREMENTS AND MAIN RESULTS: In patients with preinduction glucose above 110 mg/dL, whether or not previously treated for diabetes, perioperative insulin requirements were higher, and intraoperative insulin management was more difficult than in those with lower preinduction glucose. In patients with a preinduction glucose above 110 mg/dL, hospital stay was longer, and inhospital mortality was significantly higher than in those with lower preinduction glucose. Multivariate analyses showed that preinduction glycemia was a good predictor of intraoperative insulin consumption, as was the body mass index (BMI) for intensive care and total insulin needs. CONCLUSIONS: In cardiac surgical patients with a preinduction glucose above 110 mg/dL, even if diabetes was not previously suspected, perioperative insulin requirements were higher, and intraoperative insulin management is more difficult than in those with a preinduction glucose 110 mg/dL or lower. Preinduction glycemia and BMI are good predictors of perioperative insulin management. Preinduction glycemia above 110 mg/dL predicts difficult perioperative glucose control and, moreover, that a preinduction blood glucose of 110 mg/dL or lower is associated with less insulin need.

[Functional respiratory imaging after neostigmine- or sugammadex-enhanced recovery from neuromuscular blockade in the anesthetised rat: a randomised controlled pilot study]. / Imagem funcional da respiração após aceleração da recuperação do bloqueio neuromuscular com neostigmina ou sugamadex em ratos anestesiados: estudo piloto controlado e randomizado.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Intraoperative severity assessment of coronary artery stenosis in patients at risk: the role of transesophageal echocardiography.

A 71-yr-old male was scheduled for infrarenal abdominal aortic aneurysm repair. Although he had only minor clinical predictors for increased perioperative cardiovascular risk with >4 estimated metabolic equivalents for activities, intraoperative transesophageal echocardiography revealed an abnormal maximal-to-prestenotic blood flow velocity ratio in the left main coronary artery. Postoperatively, a severe distal left main coronary artery stenosis was confirmed with coronary angiography. Understanding the flow velocity patterns in the coronary arteries helps the anesthesiologist to detect coronary lesions with transesophageal echocardiography.

Postoperative residual paralysis in outpatients versus inpatients.

Postoperative residual paralysis is an important complication of the use of neuromuscular blocking drugs. In this prospective study, the incidence of residual paralysis detected as a train-of-four response <90% was less frequent in surgical outpatients (38%) than inpatients (47%) (P = 0.001). This might have been the result of the more frequent use of mivacurium for outpatients. Before undertaking tracheal extubation, the anesthesiologists had applied clinical criteria (outpatients, 49%; inpatients, 45%), pharmacological reversal (26%, 25%), neuromuscular transmission monitoring (12%, 11%), or a combination of these. None of these measures seemed to reduce the incidence of residual paralysis except for quantitative train-of-four monitoring. Postoperatively, eight individual clinical tests or a sum of these tests were also unable to predict residual paralysis by train-of-four. Although the incidence of residual paralysis was less frequent in surgical outpatients, predictive criteria were not evident.

Criteria for immediate postoperative extubation in adult recipients following living-related liver transplantation with total intravenous anesthesia.

STUDY OBJECTIVE: To evaluate whether our criteria for immediate postoperative extubation predicts successful extubation in living-related liver transplantation of the right lobe, and to test the effects of our standardized anesthetic technique on the success of immediate postoperative extubation. DESIGN: Open-label, descriptive study. SETTING: University hospital. PATIENTS: 6 ASA physical status III and IV patients with end-stage liver disease undergoing living-related liver transplantation of the right lobe. INTERVENTIONS: Patients received a standardized anesthetic technique with propofol, remifentanil, and cisatracurium. They were extubated when they met our criteria for immediate postoperative extubation: good donor liver function, <10 U packed red blood cells administered, hemodynamic stability, and alveolar-arterial oxygen gradient <200 mmHg. MEASUREMENTS AND MAIN RESULTS: At the end of surgery, four of the six patients fulfilled our criteria for immediate postoperative extubation. They were uneventfully extubated rapidly after surgery and soon arrived in the intensive care unit. Their postoperative stay in the operating room was only 36 minutes (range: 30 to 42 min). No patient required reintubation in the operating room or the intensive care unit. They had no recorded hemodynamic or respiratory problems postoperatively. CONCLUSIONS: Immediate extubation of selected living-related liver transplant recipients can be a safe procedure. Anesthetic management to immediate extubation seems appropriate and the derived guidelines appear acceptable.

Dose requirements and recovery profile of an infusion of cisatracurium during liver transplantation.

STUDY OBJECTIVE: To examine the dose requirements and recovery profile of an infusion of cisatracurium during liver transplantation. DESIGN: Open-label, descriptive study. SETTING: University hospital. PATIENTS: 6 ASA physical status III and IV patients with end-stage liver disease, undergoing liver transplantation. INTERVENTIONS: Neuromuscular transmission was monitored electromyographically. After recovery of T1/T0 to 10%, cisatracurium was infused at an initial rate of 1.5 microg/kg/min. The infusion rate was adjusted to maintain T1/T0 at 10%. At the end of surgery, spontaneous recovery from the neuromuscular block was awaited. MEASUREMENTS AND MAIN RESULTS: The infusion rate of cisatracurium was 1.6 +/- 0.4 microg/kg/min. Before the anhepatic phase, this rate was 1.5 +/- 0.4 microg/kg/min; during the anhepatic phase it was 1.7 +/- 0.5 microg/kg/min; and after reperfusion it was 1.9 +/- 0.4 microg/kg/min. There was a significant difference between the cisatracurium infusion rates before and after the anhepatic phase (p < 0.05). Following termination of the infusion, the time to 25% recovery of T1/T0 was 19.2 +/- 6.1 minutes, the recovery index (25% to 75%) was 28.8 +/- 7.0 minutes, and the time for the train-of-four (TOF) ratio to reach 0.7 was 50.2 +/- 7.1 minutes. The time for the TOF ratio to reach 0.9 was 61.4 +/- 6.6 minutes. There was no difference in body temperature or pH during the consecutive stages of transplantation. CONCLUSIONS: The infusion dose requirement for cisatracurium during liver transplantation tended to be higher than previously reported in healthy patients; recovery appeared prolonged. In continuous infusion of cisatracurium during liver transplantation, the tendency toward higher dose requirements, the protracted duration of infusion, the non-Hofmann elimination and/or other pharmacokinetic changes during transplantation might influence recovery from the neuromuscular block. Potential temperature or pH change during surgery seemed irrelevant in explaining the delayed recovery.