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.

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.

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.

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

Abstract 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 (0.06 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. 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.

Resumo Objetivos 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 o fluxo aéreo. Métodos 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 feitas durante o ciclo respiratório. Modelos tridimensionais dos lobos pulmonares foram gerados com 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. Resultados 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). Conclusão Este estudo piloto com ratos demonstrou uma contribuição relativa aumentada de expansão da parede torácica após neostigmina 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.

[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.

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.

Effect of sugammadex on QT/QTc interval prolongation when combined with QTc-prolonging sevoflurane or propofol anaesthesia.

BACKGROUND: We evaluated the potential for QT/corrected QT (QTc) interval prolongation after sugammadex given with propofol or sevoflurane anaesthesia. METHODS: This was a two-factorial, randomized, parallel-group study in 132 healthy subjects. Anaesthesia was maintained with sevoflurane or propofol. At ~20 min following sevoflurane/propofol initiation, sugammadex 4 mg/kg or placebo was administered. Neuromuscular blocking agents were not administered. Electrocardiograms were recorded regularly. The primary variable was the time-matched mean difference in the Fridericia-corrected QT interval (QTcF) change from baseline for sugammadex versus placebo when combined with propofol or sevoflurane. No relevant QTcF prolongation was concluded if the upper one-sided 95 % confidence interval (CI) was below the 10 ms margin of regulatory non-inferiority, up to 30 min post-study drug. Blood samples were taken for pharmacokinetic analysis. An exploratory analysis evaluated potential QT/QTc effects of neostigmine 50 µg/kg/glycopyrrolate 10 µg/kg in combination with propofol. RESULTS: The estimated mean QTcF differences between sugammadex and placebo ranged from -2.4 to 0.6 ms when combined with either anaesthetic. The largest upper one-sided 95 % CI for the mean QTcF difference between sugammadex and placebo was 2 ms, occurring 2 min post-dosing. Propofol and sevoflurane resulted in mean QTcF increases exceeding 10 and 30 ms, respectively. On top of these prolongations, the effect of sugammadex was negligible at all timepoints. The mean peak sugammadex concentration was 66.5 µg/mL, with exposure similar in the sevoflurane/propofol groups. The mean QTcF changes from baseline following neostigmine/glycopyrrolate in 10 healthy subjects ranged between -1.4 and 3.6 ms. CONCLUSION: Sugammadex 4 mg/kg does not cause clinically relevant QTc interval prolongation versus placebo when combined with propofol or sevoflurane.

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.

Perioperative blood glucose management in patients undergoing tumor hepatectomy.

STUDY OBJECTIVE: To determine whether our institutional insulin management (modified Atlanta) protocol is efficient and safe in controlling blood glucose levels in the perioperative period in surgical patients undergoing tumor hepatectomy. DESIGN: Retrospective study. SETTING: Large community hospital. PATIENTS: 20 consecutive patients undergoing liver resection for hepatocellular carcinoma, liver metastasis, or other hepatobiliary tumors. INTERVENTIONS AND MEASUREMENTS: All patients continuously received intravenous glucose (5% dextrose in water, one mL/kg/hr); insulin was administered according to a strict algorithm, and dose adjustments were based on measurements of whole-blood glucose intraoperatively at one-hour intervals, and in the intensive care unit (ICU). Lower and upper blood glucose limits were set at 85 mg/dL and 110 mg/dL, respectively, in the operating room (OR). In the ICU, lower and upper limits were 90 mg/dL and 140 mg/dL, respectively. MAIN RESULTS: Intraoperatively, 51.3% of measurements were within the target range. In the ICU, 75.2% of measurements showed a blood glucose level of 90 - 140 mg/dL. Two of 78 (2.6%) and two of 363 (0.5%) measurements had a blood glucose level < 70 mg/dL in the OR and ICU, respectively. The lowest blood glucose levels were 65 mg/dL (OR) and 66 mg/dL (ICU). CONCLUSIONS: The modified Atlanta protocol is efficient and safe in controlling blood glucose levels in the perioperative period of hepatic tumor resection. Because of decreased insulin needs in the ICU, the use of a more liberal algorithm successfully reduced the risk of hypoglycemia.

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.

Endoscopic cardiac tumor resection.

BACKGROUND: The purpose of this study is to report our 9 years' experience with endoscopic cardiac tumor resection using the port access approach. METHODS: From March 1997 to December 2005, 27 patients (mean age, 56.2 +/- 16.9 years; 70% female) underwent endoscopic cardiac tumor resection using endocardiopulmonary bypass and endoaortic-balloon clamp technique. Nineteen (70%) patients presented in New York Heart Association class I, 4 patients presented with embolic stroke, and 4 patients presented with atrial arrhythmias. All patients underwent echocardiography on admission, intraoperatively, at discharge, and at follow-up evaluation. Eight patients additionally required mitral valve replacement (n = 1), tricuspid valve replacement (n = 1), mitral valve repair (n = 2), mini-maze (n = 1), and closure of patent foramen ovale (n = 3). Mean follow-up was 3.4 +/- 2.7 years. RESULTS: Mean endoaortic-balloon clamp and endocardiopulmonary bypass times were 68.8 +/- 30.8 minutes and 112.2 +/- 41.5 minutes, respectively. There were no conversions to sternotomy. Tumors resected were classified as left atrial myxoma (n = 20), right atrial myxoma (n = 3), lipoma (n = 1), intravenous leiomyoma involving the inferior vena cava and the tricuspid valve (n = 1), plexiform tumor of the sinoatrial node (n = 1), and papillary fibroelastoma of aortic valve noncoronary cusp (n = 1). There were no hospital deaths. Mean intensive care unit and hospital stays were 1.4 +/- 1.1 days and 7.3 +/- 3.4 days, respectively. Postoperative complications were evolving stroke (n = 1), re-exploration for bleeding (n = 1), and myocardial ischemia requiring stenting (n = 1). Follow-up failed to demonstrate residual or recurrent tumor. One patient had a small residual atrial septal defect. Ninety-two percent of patients appreciated the cosmetic result and fast recovery. CONCLUSIONS: Endoscopic cardiac tumor resection is feasible and a valid oncologic approach with an attractive cosmetic advantage over median sternotomy.

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).