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|Year : 2008
: 11 | Issue : 2 | Page
|Neuromuscular blockade in cardiac surgery: An update for clinicians
Thomas M Hemmerling, Gianluca Russo, David Bracco
Department of Anaesthesiology, McGill University, Montreal General Hospital, Montreal, Canada
Click here for correspondence address and
| Abstract|| |
There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary) sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.
Keywords: Neuromuscular blockade, review, cardiac surgery
|How to cite this article:|
Hemmerling TM, Russo G, Bracco D. Neuromuscular blockade in cardiac surgery: An update for clinicians. Ann Card Anaesth 2008;11:80-90
|How to cite this URL:|
Hemmerling TM, Russo G, Bracco D. Neuromuscular blockade in cardiac surgery: An update for clinicians. Ann Card Anaesth [serial online] 2008 [cited 2020 Feb 17];11:80-90. Available from: http://www.annals.in/text.asp?2008/11/2/80/41575
| New Developments in Cardiac Surgery|| |
Cardiac surgery has undergone revolutionary changes over the last two decades that are leading to improved treatments, less invasiveness, and better outcome. Cardiac surgery has long been considered as necessitating cardiopulmonary bypass (CPB), cold electrolyte-based cardioplegia, or deep hypothermia to provide "perfect" operating conditions and organ preservation.  This technique is not devoid of complications: CPB triggers a cascade of potentially harmful body reactions, including systemic inflammation, myocardial ischaemia or dysfunction, dysrrhythmias, impairment of organ functions, such as renal, splanchnic, or pulmonary disturbances. These complications have led to the exploration of other surgical modalities that include: off-pump coronary artery bypass grafting (OPCAB), minimally invasive direct coronary artery bypass grafting (MIDCAB), totally endoscopic coronary artery bypass (TECAB), and the equivalent valve repair or replacement surgeries, as well as robotic surgery.
Off-pump coronary artery bypass grafting
The benefits of OPCAB are the elimination of CPB and aortic cannulation, shorter operating time, less use of blood products and haemodilution. In an increasingly aging patient population, the avoidance of aortic cannulation plays a significant role in decreasing postoperative morbidity, such as stroke or neurological dysfunction.  The surgical approach to OPCAB can be via conventional median sternotomy or less invasive approaches, such as thoracotomy or rib-cage lifting technique. Off-Pump Coronary Artery Bypass Grafting has the potential to decrease the time to extubation, reduce intensive care unit (ICU) or hospital length of stay, and decrease overall costs.
Minimally invasive direct coronary artery bypass
In MIDCAB technique, surgeons make an incision that is only about two inches long (as opposed to 10-12 inches fopr standard CABG) on the front of the chest, towards the left side. The approach is limited to patients requiring revascularization to the proximal left anterior descending (LAD) and specific lesions of the right coronary and circumflex arteries. Zenati et al. ,  compared this technique with conventional coronary artery bypass grafting (CABG) via median sternotomy and showed benefits of MIDCAB in terms of length of stay in intensive care unit (ICU) and hospital, as well as transfusion requirements.
In port access surgery,  a small anterior thoracotomy incision and several small "port" incisions are made on the lateral aspect of the chest allowing surgeons to view the heart through endoscopic video cameras and operate using endoscopic instruments placed in the ports [Figure 1].
The heart is either arrested during the procedure and CPB is initiated through femoral artery and vein cannulations  or off-pump methods are used.  A global application of TECAB is slow because of the technical challenges for surgeons and staff training, the prolonged learning curve extending operative and CPB times, and the prohibitive costs associated with acquiring robotic technology. 
Robotics and others
Advancements in surgical instrumentation have increased the interest in endoscopic cardiac surgery, via "keyhole" incisions. Despite some technical challenges, the development of precise and intelligent robotic-enhanced instruments has reached the point where it has become possible to do cardiac surgery that can potentially return patients to functional activity within a week after surgery. 
In addition to coronary surgery, the robotic system is used for heart valve operations, the treatment of heart failure, and rhythm management. This type of surgery might be beneficial because of better stabilization against human hand shaking, lower risk of infection, quicker recovery, and shorter hospital stay.
| Cardiac Anaesthesia|| |
Developments in anaesthesia are very often an adaptation to a changing surgical environment. It is therefore not surprising that the dramatic changes in cardiac surgical practice have caused anaesthesiologists to re-think their perioperative strategies; a faster recovery to normal function requires anaesthetic techniques which avoid a long-lasting impact on physiological functions. This can be influenced by how we manage airways, what sort of techniques we use for maintaining anaesthesia, provide perioperative analgesia, or use of muscle relaxants. On the other hand, some new cardiac surgical techniques, such as robotic surgery, actually require quite extensive anaesthetic interventions, such as single-lung ventilation for long periods of time with subsequent major pathophysiological changes.
Changes in airway management in cardiac anaesthesia
Some new surgical techniques necessitate prolonged single-lung ventilation to optimise exposure. This can cause hypoxia and hypercarbia followed by atelectasis, oedema, and ventilation perfusion mismatch.  Continuous positive airway pressure (CPAP) is applied to the collapsed lung to improve oxygenation and reduce shunt fraction if necessary, but might impair surgical vision. Correction of hypercarbia and hypoxia will be necessary to correct the changes in pulmonary artery pressures. These techniques in airway management necessitate a high level of neuromuscular blockade (NMB). Complete NMB at the diaphragm might be necessary to create an absolutely still surgical field; because NMB of the diaphragm necessitates bigger doses of neuromuscular blocking drugs (NMBDs),  repetitive doses of muscle relaxants of moderate duration of action or a continuous infusion of muscle relaxants might be preferable.
Changes in analgesia in cardiac anaesthesia
Good cardiac analgesia not only mean to provide good intraoperative haemodynamic conditions and stress protection, but also satisfactory postoperative analgesia, especially during the first 48 h after surgery. The (re-)introduction of regional techniques and shorter acting opioids for the intra- and postoperative period ,, have changed our perspective on perioperative pain control in cardiac surgery.  The use of continuous regional techniques , might also influence the necessity for intraoperative NMB which might be substantially reduced if complete analgesia is achieved.
Fast-track cardiac anaesthesia and its impact on the use of NMBDs
Myles et al. ,  consider as "fast track" all techniques, which offer extubation within 1-6 h postoperatively. Most agree with the definition that "fast track" means extubation within 8 h.  Fast-track cardiac anaesthesia incorporates early tracheal extubation, decreased length of ICU and hospital stay, and (ideally) should avoid or reduce complications to safely achieve cost-savings. Fast-track cardiac anaesthesia techniques include the use of short-acting hypnotic drugs and opioids or reduced doses of opioids. Thoracic epidural analgesia is advantageous as adjunctive analgesia to fast-track patients because of superior pain management, reduced opioid requirements, improved pulmonary function, and myocardial protection. , Fast-track cardiac surgery is possible only if short-acting NMBDs are used and normal neuromuscular transmission is achieved at the end of surgery or at the time of extubation few hours after surgery. Olivieri et al. ,  report two cases of prolonged (more than 10 h) NMB after cardiac surgery due to moderate doses of NMBDs (pancuronium 0.16 mg/kg and rocuronium 0.72 mg/kg) in combination with the use of magnesium sulfate and existing moderate renal failure. As documented by Debaene et al.,  cases of residual paralysis (train-of-four (TOF) ratio of <0.9) can occur in patients undergoing general surgery after a single-intubating dose of twice the ED95 of an NMBD with an intermediate duration of action (vecuronium, rocuronium, or atracurium). Some authors have therefore asked whether NMB is needed for cardiac surgery at all. ,,,,
As in other types of surgery with endotracheal intubation, NMB is necessary to facilitate smooth intubation conditions. In addition, NMB can aid mechanical ventilation and avoid patient movement, decrease oxygen consumption, and avoid shivering. However, NMBDs can cause certain problems in cardiac surgery: tachycardia, interaction with magnesium, inhalational agents and antibiotics, allergic reactions and postoperative residual curarisation. It is interesting to note that a national post survey in 2002 by Murphy et al. ,  revealed that pancuronium was still the primary drug used to establish and maintain NMB in patients undergoing cardiac surgery. This seems in contrast to the general practice in anaesthesia where long-acting NMBDs like pancuronium are in decline. ,,
Boluses or continuous infusion of NMBDs in cardiac surgery
Continuous NMB during surgery might precipitate postoperative residual paralysis. ,,,,, It is common, when long-acting NMBDs like pancuronium are used, ,, but is less frequent with the use of intermediate-acting NMBDs, such as cisatracurium or rocuronium. ,, One concept of NMB during cardiac surgery is the use of an initial large bolus of NMBD of intermediate action, e.g., cisatracurium (8X ED95), which then provides NMB for most of the cardiac procedure.  As the need for NMB during hypothermic CPB is significantly decreased, a continuous infusion of NMBD or frequent bolus administration might not be necessary. Cammu et al.  showed that omitting the continuous administration of NMBDs during hypothermic CPB did not increase anaesthetic requirements, the incidence of patient movements, or decrease venous oxygen saturation. The reduction of requirements of NMBDs during hypothermic CPB can be explained by complex changes in drug pharmacokinetics. 
Influence of hypothermia on NMB
Hypothermia alters the distribution and decreases the metabolism of most drugs, including NMBDs. Muscle strength is reduced during hypothermia. In addition, hypothermia has an influence on the detection of the twitch response, e.g., at the adductor pollicis. The adductor pollicis muscle temperature is primarily determined by the temperature of the blood perfusing the muscle (central temperature) and less by surface cooling effects. The muscle twitch response will therefore mainly be influenced by central body cooling. The muscle temperature can be estimated by recording central body temperature, because the difference between the two is 0.5°-1.0°C. The twitch response at the adductor pollicis muscle is proportional to the central body temperature. The duration of action of NMBDs is significantly increased by hypothermia, mainly because of a reduced elimination rate. The duration of action may increase as much as 100% when the central body temperature is reduced as little as 2°C. 
Buzello et al. ,  studied the effect of hypothermia on the characteristics of NMB induced by d-tubocurarine, alcuronium, pancuronium, and vecuronium. They found that vecuronium was the only NMBD with a consistently augmented NMB. They showed that haemodilution due to increased distribution volume was responsible for the rapid decrease of d-tubocurarine and pancuronium during hypothermic CPB. They also speculated that hypothermia might have a direct impact on NMBD action on the neuromuscular junction. Smeulers et al.  found that during hypothermic CPB, the time from the end of injection of a maintenance dose of rocuronium until twitch recovery to 5% of control (DUR5%), was approximately quadrupled, whereas the measured plasma concentration was only halved. During rewarming, the DUR5% was prolonged in comparison to pre-hypothermic CPB values by approximately 50%, whereas the plasma concentration was similar to levels obtained during hypothermic CPB. Consequently, they postulated that rocuronium requirements are greatly reduced during cooling and to a much lesser extent during rewarming.
The impairment of the metabolic function of the kidney as a result of hypoperfusion during CPB is expected to decrease renal elimination. Decreased hepatic blood flow, decreased concentration of binding proteins, and decreased intrinsic activity of the liver are assumed to diminish hepatic clearance of NMBDs during CPB.  A decreased plasma clearance of some NMBDs (rocuronium and vecuronium) during hypothermia may be explained by a change in drug disposition because of redistribution of regional blood flow. , Hypothermia also decreases acetylcholine mobilisation; smaller amounts of NMBDs are sufficient to obtain a certain degree of NMB.
The application of CPB causes electrolyte shifts. In particular, decreased plasma concentrations of magnesium and calcium result in diminished muscle contractility.
Which NMBD is for cardiac surgery?
Murphy et al.  compared pancuronium with rocuronium. Neuromuscular blockade was achieved with pancuronium (0.08-0.1 mg/kg) or rocuronium (0.6-0.8 mg/kg). Anaesthesia was maintained with isoflurane (0.2-2%). Maintenance dosing of NMB was determined on the basis of peripheral nerve stimulation of the facial nerve. The response at the muscles surrounding the eye was observed (orbicularis oculi muscle). One or two responses to TOF stimulation were maintained throughout surgery. When required, 20-30% of the initial dose of NMBD was provided as a bolus to achieve this goal. No NMBD was administered during the last half-an-hour of the case. They found that the use of rocuronium is associated with reductions in tracheal extubation times. Considering TOF ratios >0.9 as complete neuromuscular recovery, all but one of the 40 patients in the rocuronium group achieved adequate clinical recovery but, only six of the 39 patients in the pancuronium group. When weaning of ventilatory support was initiated, significant NMB was present in the pancuronium subjects (TOF ratio: median, 0.14; range: 0.00-1.11) compared with the rocuronium subjects (TOF ratio: median, 0.99; range: 0.87-1.21) ( P < 0.05). A significantly larger number of patients in the pancuronium group (32 of 39) noted at least one symptom of muscle weakness when compared with the rocuronium group (7 of 40). The most prominent symptoms were a sensation of generalised weakness, difficulties in speaking, and visual disturbances. Many patients in the pancuronium group also noted weakness in the muscles of facial expression.
It is known that volatile anaesthetics increase the potency of NMBD.  In recent years, the increased use of higher doses of volatile anaesthetics, such as sevoflurane or isoflurane have decreased the dose of NMBD necessary to maintain a certain degree of NMB.
Pharmacodynamic characteristics of the most widely available NMBD (vecuronium, rocuronium, cisatracurium, and pancuronium) are given in [Table 1].
Which NMBD is best for your needs?
Vecuronium and rocuronium decrease heart rates and might be advantageous in patients with higher baseline heart rate. Vecuronium and rocuronium provide similar intubation conditions but onset is quicker with rocuronium.  The onset time of rocuronium is the fastest onset time of NMBDs.  Cammu et al.  compared recovery time after continuous infusion of cisatracurium and rocuronium. The time interval between the end of infusion and the reappearance of a TOF ratio of 0.9 was 10 ± 9 min for cisatracurium and 18 ± 13 min for rocuronium. Although the difference was not statistically significant, the authors concluded that cisatracurium might be safer after continuous administration. Especially if higher dose of opioids are used for induction - thus creating the possibility of thoracic rigidity - NMBDs with faster onset, such as rocuronium, might be of help.  Therefore, many authors choose between two intermediate acting NMBDs: rocuronium or cisatracurium. Cisatracurium can be administered to facilitate intubation; however, it has a rather long onset time comparable or even longer than vecuronium or pancuronium. However, its recovery index is slightly shorter than for rocuronium or any other NMBD in cardiac surgery. Cisatracurium does provide superior haemodynamic stability, does not release histamine and its metabolism via Hoffman elimination is independent of organ function.
If further relaxation is required, additional boluses can be given adjusting the right dose by neuromuscular monitoring. Boluses are, in general, preferable for all NMBDs. When neuromuscular blockade is not monitored, there might be a delay in neuromuscular recovery, even after NMBD with intermediate duration of action, such as rocuronium. 
Continuous infusion of NMBDs in cardiac surgery
To achieve a constant level of NMB, some authors have advocated the use of continuous infusion of NMBDs [Table 2]. Ouattara  proposed cisatracurium (1.1-3.2 ”g/kg/min) after an i.v. bolus of 0.15-0.3 mg/kg; Cammu  gave cisatracurium (0.1 mg/kg) for induction followed, after 30 min, by an infusion begun at a rate of 1 ”g/kg/min before CPB, continued at a rate of 0.75 ”g/kg/min during CPB, and resumed at 1 ”g/kg/min following CPB. More sophisticated infusion protocols, adapting the infusion rate to different states of cardiac surgery (before, during, and after CPB), have been proposed by Cammu  and Kansanaho  with the purpose to reduce postoperative NMB.
Haemodynamic stability of NMBDs
Pancuronium has been found to have cardiovascular stimulating properties [Table 3]. ,,, These are the result of a vagolytic effect on muscarinic receptors, increases in norepinephrine release, and blockade of norepinephrine re-uptake at the sympathetic nerve terminals. However, tachycardia increases oxygen consumption and compromises coronary flow by reducing diastolic perfusion time. Pancuronium, in dogs, caused an increased pulmonary arterial pressure (PAP) due to increased cardiac output and pulmonary vascular resistance.  Pancuronium's effect on systemic pressure may not be as important as its effects on the heart rate. ,,, Virmani et al. ,  compared pancuronium with rocuronium and vecuronium; they found significant tachycardia 1 min after injection of pancuronium and this effect persisted throughout the study period (up to 5 min after intubation) with a maximum increase to 140.8 ± 35 beats/min, 1 min after intubation. Rocuronium and vecuronium decreased the heart rate 1 min after injection with the maximum decrease at 83.8 ± 19.6 beats/min, 5 min after injection.  In contrast to a case report where the concomitant use of sufentanil and vecuronium caused severe bradycardia and asystole,  Virmani et al. , observed that the decrease in heart rate caused by rocuronium and vecuronium was not clinically significant, and hence did not require any treatment. McCoy et al. and Hudson et al. , , note that both, rocuronium and vecuronium, decrease pulmonary artery pressure. Cisatracurium has no important haemodynamic side effects. One study showed, that there is no evidence of a haemodynamic difference between cisatracurium and vecuronium.  Other studies, as Konstadt et al.  emphasise advantages of cisatracurium compared with vecuronium, particularly when used in patients with significant cardiovascular disease because of its haemodynamic stability.
| Residual Paralysis in Cardiac Surgery|| |
Residual paralysis in cardiac surgery is an important side effect in the postoperative period and an important reason for delayed extubation.  The high incidence of postoperative residual paralyis after cardiac surgery might also be due to the fact that many anaesthetists focus more on haemodynamic management during cardiac surgery, might not always consider fast-tracking patients in the postoperative period as their priority of care and still very often use long-acting NMBDs, such as pancuronium, with potential for accumulation. To exploit the beneficial effects of early extubation, intraoperative neuromuscular monitoring, , and the use of short- or intermediate-acting NMBDs is vital. Van Oldenbeek et al.  studied residual NMB caused by pancuronium after cardiac surgery. Neuromuscular block was measured electromyographically at the adductor pollicis at 5 min intervals until TOF reached 0.8. They found that, in spite of having received only relatively modest doses of pancuronium (median = 0.11 mg/kg total), 13 of 20 patients demonstrated a considerable degree of residual block (median: TOF = 0.23) in the ICU when extubation was planned 2 h after surgery. Baillard et al.  studied postoperative residual paralysis (defined as a TOF ratio <7) after vecuronium in 568 patients undergoing different types of surgery. Thirty-three percent of patients had a TOF ratio <0.7 on arrival in the recovery room. In that study, neuromuscular monitoring was performed in only 11 out of 568 patients. The reason of postoperative residual paralysis in that study might therefore be more caused by the absence of neuromuscular monitoring than the pharmacokinetic proprieties of vecuronium. Murphy in 2002  showed that tracheal extubation was significantly delayed when pancuronium was used (median, 500 min; range: 240-1305 min) compared with rocuronium (median, 350 min; range: 210-1140 min), thus confirming results from previous studies. ,
Similar advantages are found when cisatracurium is compared with pancuronium , and vecuronium  Even when cisatracurium-induced NMB was maintained by a continuous infusion of 1.1-3.2 ”g/kg/min, 83% of patients were successfully extubated at a TOF ratio of >0.9 measured at adductor pollicis muscle within 8 h of cardiac surgery. 
Reversal drugs for NMB
Some authors suggest residual paralysis can be reduced if NMBDs are routinely reversed before extubation is attempted.  In the recent survey by Murphy et al. , about the use of NMB in cardiac surgery, only 9% of the respondents reported that NMB was routinely reversed before tracheal extubation in the ICU.  It is likely that most clinicians believe that neuromuscular function will fully recover spontaneously by the time weaning and tracheal extubation are accomplished; however, when long-acting NMBDs are used, available data do not support this belief. , In addition, communication between ICU staff and cardiac anaesthesiologists may be insufficient, or ICU staff not familiar with reversal of NMBDs.
Most commonly used reversal agents are inhibitors of acetylcholinesterase (AChE), such as neostigmine, edrophonium, and pyridostigmine. The mechanism of action of these drugs is to increase the level of acetylcholine at the neuromuscular junction by inhibiting the breakdown of acetylcholine. The use of AChE inhibitors as reversal agents leads to problems with selectivity, as neurotransmission to all synapses (both somatic and autonomic) involving the neurotransmitter acetylcholine is potentiated. This nonselectivity may lead to side effects, including bradycardia, hypotension, increased salivation, nausea, vomiting, abdominal cramps, diarrhea, and bronchoconstriction. Therefore, these agents should be used only after or together with the administration of glycopyrrolate or atropine to antagonise the muscarinic effects of acetylcholine. The use of a muscarinic acetylcholine receptor (mAChR) antagonist can by itself cause a number of side effects, e.g., tachycardia, dry mouth, blurred vision, difficulties in emptying the bladder, and it may also affect cardiac conduction.
In the early postoperative period, patients with cardiovascular disease are at increased risk of ischaemia secondary to pain, tachycardia, shivering, hypothermia, hypoxia, hypertension, and hypotension.  Thus, impaired parasympathetic control during this high-risk period could increase the risk of ischaemia and dysrrhythmias. Patients with underlying diseases of the cardiovascular system exhibit a baseline impairment of parasympathetic control and cardiac baroreflex sensitivity.  It is conceivable that further deterioration of parasympathetic control in the postoperative period by using reversal drugs could result in a more profound or prolonged state of vulnerability in patients at risk of myocardial ischaemia. However, it should be stressed that although a strong association exists, a cause-and-effect relationship between parasympathetic nervous system impairment and cardiac complications has not been proved.
The effects of glycopyrrolate appear to be of shorter duration; thus, this drug may be preferable in patients at risk of cardiovascular complications. Van Vlymen et al.  showed that the heart rate, blood pressure and respiratory rate remain impaired for at least 120 min into the postoperative period after the administration of atropine (20 ”g/kg) and neostigmine (50 ”g/kg), but were restored quickly after glycopyrrolate (8 ”g/kg) and neostigmine (50 ”g/kg).
Sugammadex in cardiac surgery
Sugammadex is a new, modified g-cyclodextrin compound ready to be launched in 2009.
Because of its mechanism of action, it does not involve direct interaction with the cholinergic system, but acts by rapidly encapsulating a steroidal NMBD, such as rocuronium (to a much less extent vecuronium) and forming a stable complex that prevents the pharmacological action of the NMBD at the neuromuscular junction. Reversal with sugammadex is not accompanied by any cardiovascular adverse effects usually seen with acetylcholinesterase (AChE) inhibitors and does not require the co-administration of anticholinergic agents.  It is effective in reversing NMB induced by single-intubating doses of rocuronium in both healthy volunteers and surgical patients. Shields et al.  studied the dose-response relation and safety of sugammadex for reversal of a prolonged rocuronium-induced NMB in 30 anaesthetised adult patients. They assigned 0.5, 1.0, 2.0, 4.0, or 6.0 mg/kg of sugammadex at recovery of T2 of the TOF-ratio, following at least 2 h of NMB. The main end-point of the study was the time to achieve a sustained recovery of TOF ratio to 0.9. Recovery occurred within 4 min with all doses of sugammadex from 1.0 to 6.0 mg/kg, and within 3 min at doses of 2.0-4.0 mg/kg. Whatever place sugammadex will take in the anaesthetic arsenal in the future, its use in cardiac surgery will certainly be one of its key indications.
Which monitoring is best for NMB in cardiac surgery?
Monitoring in cardiac anaesthesia helps to maintain the right level of NMB during surgery; especially during CPB. It might permit us to give less NMBD and reduce postoperative paralysis. 
It is important to monitor the right muscle to obtain different information. It has been demonstrated that recovery of neuromuscular transmission is best monitored at the adductor pollicis muscle, as it is the last muscle to recover from NMB. During surgery, monitoring the corrugator supercilii muscle reflects best NMB at more profound or central muscles, such as larynx, diaphragm,  or abdominal muscles.  It is best suited to determine the degree of NMB in cardiac surgery at the site of surgery - the thoracic cavity. Proper monitoring should be to use one of the available objective monitoring methods. For clinical routine, acceleromyography and kinemyography are best suited.
Acceleromyography is easy to apply, can be used with data processing devices, and is relatively inexpensive [Figure 2]. It shows good agreement with mechanomyography when the set-up is carefully prepared. However, its use at smaller muscles, such as the corrugator supercilii muscle, necessitates special transducer probes and device set-up. At present, acceleromyography is the best combination of a simple, accurate, and reliable monitoring method commercially available to measure NMB objectively in routine clinical settings. ,
Recently, a neuromuscular monitoring device has entered the market, integrated into the Datex Ohmeda Aestiva anaesthetic machine (Datex Ohmeda Inc, Madison, WI, USA). The device uses kinemyography, and is based on the measuring the movement of thumb [Figure 3]. Kinemyography employs a piezo-electric transducer and consists of a molded plastic device which mirrors the contour of the outstretched thumb and index finger. One study has shown that this device agrees reasonably with mechanomyography for monitoring TOF-ratios, but other pharmacodynamic responses do not agree well with the MMG. The response, especially during the recovery of neuromuscular function, can be misleading.  However, it is reasonably precise and easy-to-use for cardiac surgery; but monitoring the corrugator supercilii muscle is not possible.
| Conclusions|| |
In recent decades, cardiac surgery has delivered fundamental changes and advancements which all impact on how we administer cardiac anaesthesia. Minimally invasive cardiac surgery and OPCAB have changed the practice of cardiac surgery towards faster recovery with less morbidity. These changes affect all aspects of cardiac anaesthesia, including the use of NMBDs and neuromuscular monitoring.
There is common agreement of the need of continuous neuromuscular monitoring during cardiac surgery; this can best be achieved at present - combining ease of use, reliability of results, applicability at different muscles, availability of monitoring device - using acceleromyography. Monitoring sites should include the adductor pollicis muscle, reflecting more peripheral muscles and one of the last muscles to recover from NMB, and the corrugator supercilii muscle, reflecting NMB at more profound, central muscles, such as diaphragm of thoracic cavity muscles.
There is no valid reason for using pancuronium still; its pharmacodynamic and pharmacokinetic profiles make it inappropriate for cardiac surgery. Rocuronium and cisatracurium are the best choices for NMB during cardiac surgery; cisatracurium should be preferred whenever haemodynamic stability and/or organ-independent metabolism is important. Continuous infusions of NMBDs carry the increased risk of postoperative residual muscle paralysis and should therefore be avoided or used with great care and continuous objective neuromuscular monitoring. Reversal after NMB contradicts the concept of titration of NMBDs. Proper management of NMB throughout surgery, pre-emptive thinking whenever NMBDs are applied at later stages of cardiac surgery, and objective neuromuscular monitoring help to avoid the use of reversal drugs which might impair haemodynamic stability. Whether extubation is immediate, early, or late, no patient should be extubated without verification of normal neuromuscular transmission; this might necessitate teaching ICU staff - if they are not anaesthesiologists - the proper use of neuromuscular monitoring devices. Sugammadex might find its place in cardiac surgery, but is no substitute for proper administration and monitoring of current NMBDs.
| References|| |
|1.||Earp JK, Mallia G. Myocardial protection for cardiac surgery: The nursing perspective. AACN Clin Issues 1997;8:20-32. [PUBMED] [FULLTEXT]|
|2.||Yamada T, Ochiai R, Takeda J. Anesthetic management during minimally invasive cardiac surgery with the Port-Access system for closure of atrial septal defect. J Anesth 2000;14:98-101. [PUBMED] [FULLTEXT]|
|3.||Zenati M, Domit TM, Saul M, Gorcsan J 3 rd , Katz WE, Hudson M, et al . Resource utilization for minimally invasive direct and standard coronary artery bypass grafting. Ann Thorac Surg 1997;63:S84-7. |
|4.||Lapierre H, Chan V, Ruel M. Off-pump coronary surgery through mini-incisions: Is it reasonable? Curr Opin Cardiol 2006;21:578-83. [PUBMED] [FULLTEXT]|
|5.||Miga KC. Trends in cardiac surgery: Exploring the past and looking into the future. Crit Care Nurs Clin North Am 2007;19:343-51v. [PUBMED] [FULLTEXT]|
|6.||Dogan S, Aybek T, Mierdl S, Wimmer-Greinecker G. Totally endoscopic coronary artery bypass grafting on the arrested heart is a prerequisite for successful totally endoscopic beating heart coronary revascularisation. Interact Cardiovasc Thorac Surg 2002;1:30-4. [PUBMED] [FULLTEXT]|
|7.||Ganapathy S. Anaesthesia for minimally invasive cardiac surgery. Best Pract Res Clin Anaesthesiol 2002;16:63-80. [PUBMED] |
|8.||Hemmerling TM, Donati F. Neuromuscular blockade at the larynx, the diaphragm and the corrugator supercilii muscle: A review. Can J Anaesth 2003;50:779-94. [PUBMED] [FULLTEXT]|
|9.||Myles PS, McIlroy D. Fast-track cardiac anesthesia: Choice of anesthetic agents and techniques. Semin Cardiothorac Vasc Anesth 2005;9:5-16. [PUBMED] [FULLTEXT]|
|10.||Bracco D, Noiseux N, Dubois MJ, Prieto I, Basile F, Olivier JF, et al . Epidural anesthesia improves outcome and resource use in cardiac surgery: A single-center study of a 1293-patient cohort. Heart Surg Forum 2007;10:E449-58. [PUBMED] [FULLTEXT]|
|11.||Chaney MA. Intrathecal and epidural anesthesia and analgesia for cardiac surgery. Anesth Analg 2006;102:45-64. [PUBMED] [FULLTEXT]|
|12.||Roediger L, Larbuisson R, Lamy M. New approaches and old controversies to postoperative pain control following cardiac surgery. Eur J Anaesthesiol 2006;23:539-50. [PUBMED] [FULLTEXT]|
|13.||Hemmerling TM, Djaiani G, Babb P, Williams JP. The use of epidural analgesia in cardiac surgery should be encouraged. Anesth Analg 2006;103:1592-3. [PUBMED] [FULLTEXT]|
|14.||Myles PS, Daly DJ, Djaiani G, Lee A, Cheng DC. A systematic review of the safety and effectiveness of fast-track cardiac anesthesia. Anesthesiology 2003;99:982-7. [PUBMED] [FULLTEXT]|
|15.||Miller. Miller's anesthesia. Elsevier; 2006; p 1970. |
|16.||Hemmerling TM, Prieto I, Choiniere JL, Basile F, Fortier JD. Ultra-fast-track anesthesia in off-pump coronary artery bypass grafting: A prospective audit comparing opioid-based anesthesia vs thoracic epidural-based anesthesia. Can J Anaesth 2004;51:163-8. |
|17.||Crescenzi G, Covello RD, Landoni G, De Luca M, Fracasso G, Melone M, et al . Thoracic epidural anaesthesia in valvular cardiac surgery. Eur J Anaesthesiol 2008;25:339-40. [PUBMED] [FULLTEXT]|
|18.||Olivieri L, Plourde G. Prolonged (more than ten hours) neuromuscular blockade after cardiac surgery: Report of two cases. Can J Anaesth 2005;52:88-93. [PUBMED] [FULLTEXT]|
|19.||Debaene B, Plaud B, Dilly MP, Donati F. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology 2003;98:1042-8. [PUBMED] |
|20.||Cammu G. How rational is muscle relaxation during cardiac surgery? Acta Anaesthesiol Belg 2007;58:7-14. [PUBMED] |
|21.||Hemmerling TM, Olivier JF. In off-pump cardiac surgery, neuromuscular monitoring should be mandatory and immediate extubation is feasible. Eur J Anaesthesiol 2004;21:322-3. |
|22.||Fleming N. Con: The choice of muscle relaxants is not important in cardiac surgery. J Cardiothorac Vasc Anesth 1995;9:772-4. [PUBMED] [FULLTEXT]|
|23.||Hudson ME, Rothfield KP, Tullock WC, Firestone LL. Haemodynamic effects of rocuronium bromide in adult cardiac surgical patients. Can J Anaesth 1998;45:139-43. [PUBMED] [FULLTEXT]|
|24.||Gueret G, Rossignol B, Kiss G, Wargnier JP, Miossec A, Spielman S, et al . Is muscle relaxant necessary for cardiac surgery? Anesth Analg 2004;99:1330-3. [PUBMED] [FULLTEXT]|
|25.||Murphy GS, Szokol JW, Vender JS, Marymont JH, Avram MJ. The use of neuromuscular blocking drugs in adult cardiac surgery: Results of a national postal survey. Anesth Analg 2002;95:1534-9. [PUBMED] [FULLTEXT]|
|26.||Murphy GS, Szokol JW, Marymont JH, Avram MJ, Vender JS, Rosengart TK. Impact of shorter-acting neuromuscular blocking agents on fast-track recovery of the cardiac surgical patient. Anesthesiology 2002;96:600-6. [PUBMED] |
|27.||McEwin L, Merrick PM, Bevan DR. Residual neuromuscular blockade after cardiac surgery: Pancuronium vs rocuronium. Can J Anaesth 1997;44:891-5. [PUBMED] [FULLTEXT]|
|28.||Murphy GS, Szokol JW, Marymont JH, Vender JS, Avram MJ, Rosengart TK, et al . Recovery of neuromuscular function after cardiac surgery: Pancuronium versus rocuronium. Anesth Analg 2003;96:1301-7. [PUBMED] [FULLTEXT]|
|29.||Ouattara A, Richard L, Charriere JM, Lanquetot H, Corbi P, Debaene B. Use of cisatracurium during fast-track cardiac surgery. Br J Anaesth 2001;86:130-2. |
|30.||Smith CE, Botero C, Holbrook C, Pinchak AC, Hagen JF. Rocuronium versus vecuronium during fentanyl induction in patients undergoing coronary artery surgery. J Cardiothorac Vasc Anesth 1999;13:567-73. [PUBMED] [FULLTEXT]|
|31.||Van Oldenbeek C, Knowles P, Harper NJ. Residual neuromuscular block caused by pancuronium after cardiac surgery. Br J Anaesth 1999;83:338-9. [PUBMED] [FULLTEXT]|
|32.||Cammu G, Coddens J, Hendrickx J, Deloof T. Dose requirements of infusions of cisatracurium or rocuronium during hypothermic cardiopulmonary bypass. Br J Anaesth 2000;84:587-90. [PUBMED] [FULLTEXT]|
|33.||Cammu G, Boussemaere V, Foubert L, Hendrickx J, Coddens J, Deloof T. Large bolus dose vs. continuous infusion of cisatracurium during hypothermic cardiopulmonary bypass surgery. Eur J Anaesthesiol 2005;22:25-9. |
|34.||Cammu G, Cardinael S, Lahousse S, Eecke GV, Coddens J, Foubert L, et al . Muscle relaxation does not influence venous oxygen saturation during cardiopulmonary bypass. J Clin Anesth 2007;19:105-1 [PUBMED] [FULLTEXT]|
|35.||Rosen DA, Rosen KR. Elimination of drugs and toxins during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997;11:337-40. [PUBMED] [FULLTEXT]|
|36.||Heier T, Caldwell JE. Impact of hypothermia on the response to neuromuscular blocking drugs. Anesthesiology 2006;104:1070-80. [PUBMED] [FULLTEXT]|
|37.||Buzello W, Schluermann D, Pollmaecher T, Spillner G. Unequal effects of cardiopulmonary bypass-induced hypothermia on neuromuscular blockade from constant infusion of alcuronium, d-tubocurarine, pancuronium, and vecuronium. Anesthesiology 1987;66:842-6. [PUBMED] |
|38.||Smeulers NJ, Wierda JM, van den Broek L, Gallandat Huet RC, Hennis PJ. Effects of hypothermic cardiopulmonary bypass on the pharmacodynamics and pharmacokinetics of rocuronium. J Cardiothorac Vasc Anesth 1995;9:700-5. [PUBMED] [FULLTEXT]|
|39.||Buylaert WA, Herregods LL, Mortier EP, Bogaert MG. Cardiopulmonary bypass and the pharmacokinetics of drugs: An update. Clin Pharmacokinet 1989;17:10-26. [PUBMED] |
|40.||Smeulers NJ, Wierda JM, van den Broek L, Gallandat Huet RC, Hennis PJ. Hypothermic cardiopulmonary bypass influences the concentration-response relationship and the biodisposition of rocuronium. Eur J Anaesthesiol Suppl 1995;11:91-4. [PUBMED] |
|41.||Cammu G. Interactions of neuromuscular blocking drugs. Acta Anaesthesiol Belg 2001;52:357-63. [PUBMED] |
|42.||Sparr HJ, Beaufort TM, Fuchs-Buder T. Newer neuromuscular blocking agents: How do they compare with established agents? Drugs 2001;61:919-42. [PUBMED] |
|43.||Cammu G, de Baerdemaeker L, den Blauwen N, de Mey JC, Struys M, Mortier E. Postoperative residual curarization with cisatracurium and rocuronium infusions. Eur J Anaesthesiol 2002;19:129-34. [PUBMED] |
|44.||Kansanaho M, Hynynen M, Olkkola KT. Model-driven closed-loop feedback infusion of atracurium and vecuronium during hypothermic cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997;11:58-61. [PUBMED] [FULLTEXT]|
|45.||Ferres CJ, Carson IW, Lyons SM, Orr IA, Patterson CC, Clarke RS. Haemodynamic effects of vecuronium, pancuronium and atracurium in patients with coronary artery disease. Br J Anaesth 1987;59:305-11. [PUBMED] |
|46.||Virmani S, Tempe DK, Datt V, Tomar AS, Banerjee A, Minhas HS, et al . Effect of muscle relaxants on heart rate, arterial pressure, intubation conditions and onset of neuromuscular block in patients undergoing valve surgery. Ann Card Anaesth 2006;9:37-43. |
|47.||Sethna DH, Starr NJ, Estafanous FG. Cardiovascular effects of non-depolarizing neuromuscular blockers in patients with aortic valve disease. Can J Anaesth 1987;34:582-8. [PUBMED] [FULLTEXT]|
|48.||Paulissian R, Mahdi M, Joseph NJ, Salem MR, Pavlovich B, Crystal GJ. Hemodynamic responses to pancuronium and vecuronium during high-dose fentanyl anesthesia for coronary artery bypass grafting. J Cardiothorac Vasc Anesth 1991;5:120-5. [PUBMED] |
|49.||Du H, Orii R, Yamada Y, Hayashida M, Kin N, Suwa K, et al . Pancuronium increases pulmonary arterial pressure in lung injury. Br J Anaesth 1996;77:526-9. [PUBMED] [FULLTEXT]|
|50.||Starr NJ, Sethna DH, Estafanous FG. Bradycardia and asystole following the rapid administration of sufentanil with vecuronium. Anesthesiology 1986;64:521-3. [PUBMED] |
|51.||McCoy EP, Maddineni VR, Elliott P, Mirakhur RK, Carson IW, Cooper RA. Haemodynamic effects of rocuronium during fentanyl anaesthesia: Comparison with vecuronium. Can J Anaesth 1993;40:703-8. [PUBMED] [FULLTEXT]|
|52.||Searle NR, Thomson I, Dupont C, Cannon JE, Roy M, Rosenbloom M, et al . A two-center study evaluating the hemodynamic and pharmacodynamic effects of cisatracurium and vecuronium in patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth 1999;13:20-5. [PUBMED] [FULLTEXT]|
|53.||Konstadt SN, Reich DL, Stanley TE 3 rd , DePerio M, Chuey C, Schwartzbach C, et al . A two-center comparison of the cardiovascular effects of cisatracurium (Nimbex) and vecuronium in patients with coronary artery disease. Anesth Analg 1995;81:1010-4. |
|54.||Wong DT, Cheng DC, Kustra R, Tibshirani R, Karski J, Carroll-Munro J, et al . Risk factors of delayed extubation, prolonged length of stay in the intensive care unit, and mortality in patients undergoing coronary artery bypass graft with fast-track cardiac anesthesia: A new cardiac risk score. Anesthesiology 1999;91:936-44. [PUBMED] [FULLTEXT]|
|55.||Gatke MR, Viby-Mogensen J, Rosenstock C, Jensen FS, Skovgaard LT. Postoperative muscle paralysis after rocuronium: Less residual block when acceleromyography is used. Acta Anaesthesiol Scand 2002;46:207-13. |
|56.||Baillard C, Gehan G, Reboul-Marty J, Larmignat P, Samama CM, Cupa M. Residual curarization in the recovery room after vecuronium. Br J Anaesth 2000;84:394-5. [PUBMED] [FULLTEXT]|
|57.||O'Connor JP, Ramsay JG, Wynands JE, Ralley FE, Casey WF, Smith CE, et al . The incidence of myocardial ischemia during anesthesia for coronary artery bypass surgery in patients receiving pancuronium or vecuronium. Anesthesiology 1989;70:230-6. [PUBMED] |
|58.||Rauch H, Jung I, Fleischer F, Bauer H, Martin E, Motsch J. Cisatracurium in coronary bypass operations-a comparison with pancuronium: Hemodynamic and neuromuscular effects in patients under chronic beta blocker treatment. Anaesthesist 2001;50:87-93. [PUBMED] [FULLTEXT]|
|59.||Reich DL, Hollinger I, Harrington DJ, Seiden HS, Chakravorti S, Cook DR. Comparison of cisatracurium and vecuronium by infusion in neonates and small infants after congenital heart surgery. Anesthesiology 2004;101:1122-27. [PUBMED] |
|60.||van Vlymen JM, Parlow JL. The effects of reversal of neuromuscular blockade on autonomic control in the perioperative period. Anesth Analg 1997;84:148-54. [PUBMED] [FULLTEXT]|
|61.||Nicholson WT, Sprung J, Jankowski CJ. Sugammadex: A novel agent for the reversal of neuromuscular blockade. Pharmacotherapy 2007;27:1181-8. [PUBMED] [FULLTEXT]|
|62.||hields M, Giovannelli M, Mirakhur RK, Moppett I, Adams J, Hermens Y. Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block. Br J Anaesth 2006;96:36-43. [PUBMED] [FULLTEXT]|
|63.||Kirov K, Motamed C, Ndoko SK, Dhonneur G. TOF count at corrugator supercilii reflects abdominal muscles relaxation better than at adductor pollicis. Br J Anaesth 2007;98:611-4. [PUBMED] [FULLTEXT]|
|64.||Hemmerling TM, Le N. Brief review: Neuromuscular monitoring: An update for the clinician. Can J Anaesth 2007;54:58-72. [PUBMED] [FULLTEXT]|
|65.||Eriksson LI. Evidence-based practice and neuromuscular monitoring: It's time for routine quantitative assessment. Anesthesiology 2003;98:1037-9. [PUBMED] [FULLTEXT]|
|66.||Bluestein LS, Stinson LW Jr, Lennon RL, Quessy SN, Wilson RM. Evaluation of cisatracurium: A new neuromuscular blocking agent, for tracheal intubation. Can J Anaesth 1996;43:925-31. [PUBMED] [FULLTEXT]|
|67.||Magorian T, Flannery KB, Miller RD. Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients. Anesthesiology 1993;79:913-8. [PUBMED] |
|68.||Lebowitz PW, Ramsey FM, Savarese JJ, Ali HH, deBros FM. Combination of pancuronium and metocurine: Neuromuscular and hemodynamic advantages over pancuronium alone. Anesth Analg 1981;60:12-7. [PUBMED] [FULLTEXT]|
|69.||Hemmerling TM, Schmidt J, Schurr C, Breuer G, Jacobi KE. A comparison between anterior and posterior monitoring of neuromuscular blockade at the diaphragm: Both sites can be used interchangeably. Anesth Analg 2002;95:940-3. [PUBMED] [FULLTEXT]|
|70.||Kim KS, Chung CW, Shin WJ. Cisatracurium neuromuscular block at the adductor pollicis and the laryngeal adductor muscles in humans. Br J Anaesth 1999;83:483-4. [PUBMED] [FULLTEXT]|
|71.||Hilgenberg JC. Comparison of the pharmacology and vecuronium and atracurium with that of other currently available muscle relaxants. Anesth Analg 1983;62:524-31. [PUBMED] [FULLTEXT]|
|72.||Foldes FF, Nagashima H, Nguyen HD, Schiller WS, Mason MM, Ohta Y. The neuromuscular effects of ORG9426 in patients receiving balanced anesthesia. Anesthesiology 1991;75:191-6. [PUBMED] |
|73.||Naguib M, Samarkandi AH, Ammar A, Elfaqih SR, Al-Zahrani S, Turkistani A. Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination. Anesthesiology 1998;89:1116-24. [PUBMED] [FULLTEXT]|
|74.||Fahey MR, Morris RB, Miller RD, Nguyen TL, Upton RA. Pharmacokinetics of Org NC45 (norcuron) in patients with and without renal failure. Br J Anaesth 1981;53:1049-53. |
|75.||Naguib M, Samarkandi AH, Bakhamees HS, Magboul MA, el-Bakry AK. Comparative potency of steroidal neuromuscular blocking drugs and isobolographic analysis of the interaction between rocuronium and other aminosteroids. Br J Anaesth 1995;75:37-42. [PUBMED] [FULLTEXT]|
|76.||Krieg N, Crul JF, Booij LH. Relative potency of ORG NC 45, pancuronium, alcuronium and tubocurarine in anaesthetized man. Br J Anaesth 1980;52:783-8. [PUBMED] [FULLTEXT]|
|77.||Rautoma P, Erkola O, Meretoja OA. Potency and hourly maintenance requirement of combinations of mivacurium and pancuronium in adults. Can J Anaesth 1998;45:212-6. [PUBMED] [FULLTEXT]|
|78.||Jellish WS, Brody M, Sawicki K, Slogoff S. Recovery from neuromuscular blockade after either bolus and prolonged infusions of cisatracurium or rocuronium using either isoflurane or propofol-based anesthetics. Anesth Analg 2000;91:1250-5. [PUBMED] [FULLTEXT]|
|79.||Keles GT, Yentur A, Cavus Z, Sakarya M. Assessment of neuromuscular and haemodynamic effects of cisatracurium and vecuronium under sevoflurane-remifentanil anaesthesia in elderly patients. Eur J Anaesthesiol 2004;21:877-81. |
|80.||Rorvik K, Husby P, Gramstad L, Vamnes JS, Bitsch-Larsen L, Koller ME. Comparison of large dose of vecuronium with pancuronium for prolonged neuromuscular blockade. Br J Anaesth 1988;61:180-5. |
|81.||Roizen MF, Feeley TW. Pancuronium bromide. Ann Intern Med 1978;88:64-8. [PUBMED] |
|82.||Khuenl-Brady K, Castagnoli KP, Canfell PC, Caldwell JE, Agoston S, Miller RD. The neuromuscular blocking effects and pharmacokinetics of ORG 9426 and ORG 9616 in the cat. Anesthesiology 1990;72:669-74. [PUBMED] |
|83.||Sandker GW, Weert B, Olinga P, Wolters H, Slooff MJ, Meijer DK, et al . Characterization of transport in isolated human hepatocytes: A study with the bile acid taurocholic acid, the uncharged ouabain and the organic cations vecuronium and rocuronium. Biochem Pharmacol 1994;47:2193-200. [PUBMED] [FULLTEXT]|
|84.||Kisor DF, Schmith VD, Wargin WA, Lien CA, Ornstein E, Cook DR. Importance of the organ-independent elimination of cisatracurium. Anesth Analg 1996;83:1065-71. [PUBMED] [FULLTEXT]|
|85.||Caldwell JE, Szenohradszky J, Segredo V, Wright PM, McLoughlin C, Sharma ML, et al . The pharmacodynamics and pharmacokinetics of the metabolite 3-desacetylvecuronium (ORG 7268) and its parent compound, vecuronium, in human volunteers. J Pharmacol Exp Ther 1994;270:1216-22. [PUBMED] [FULLTEXT]|
|86.||Agoston S, Vermeer GA, Kertsten UW, Meijer DK. The fate of pancuronium bromide in man. Acta Anaesthesiol Scand 1973;17:267-75. [PUBMED] |
|87.||Mol WE, Meijer DK. Hepatic transport mechanisms for bivalent organic cations. Subcellular distribution and hepato-biliary concentration gradients of some steroidal muscle relaxants. Biochem Pharmacol 1990;39:383-90. |
|88.||Moore EW, Hunter JM. The new neuromuscular blocking agents: Do they offer any advantages? Br J Anaesth 2001;87:912-25. [PUBMED] [FULLTEXT]|
|89.||Caldwell JE, Castagnoli KP, Canfell PC, Fahey MR, Lynam DP, Fisher DM, et al . Pipecuronium and pancuronium: Comparison of pharmacokinetics and duration of action. Br J Anaesth 1988;61:693-7. [PUBMED] |
|90.||Robertson EN, Driessen JJ, Booij LH. Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure. Eur J Anaesthesiol 2005;22:4-10. [PUBMED] |
|91.||Soukup J, Czeslick E, Bunk S, Clausen T, Menzel M, Radke J. Cisatracurium in patients with compromised kidney function: Pharmacodynamic and intubation conditions under isoflurane-nitrous oxide anesthesia. Anaesthesist 1998;47:669-76. [PUBMED] [FULLTEXT]|
|92.||Della Rocca G, Pompei L, Coccia C, Costa MG, Cecchini V, Vilardi V, et al . Atracurium, cisatracurium, vecuronium and rocuronium in patients with renal failure. Minerva Anestesiol 2003;69:605-11. [PUBMED] [FULLTEXT]|
|93.||Duvaldestin P, Agoston S, Henzel D, Kersten UW, Desmonts JM. Pancuronium pharmacokinetics in patients with liver cirrhosis. Br J Anaesth 1978;50:1131-6. [PUBMED] [FULLTEXT]|
|94.||van Miert MM, Eastwood NB, Boyd AH, Parker CJ, Hunter JM. The pharmacokinetics and pharmacodynamics of rocuronium in patients with hepatic cirrhosis. Br J Clin Pharmacol 1997;44:139-44. [PUBMED] [FULLTEXT]|
|95.||De Wolf AM, Freeman JA, Scott VL, Tullock W, Smith DA, Kisor DF, et al . Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end-stage liver disease undergoing liver transplantation. Br J Anaesth 1996;76:624-8. [PUBMED] [FULLTEXT]|
|96.||Levy JH, Davis GK, Duggan J, Szlam F. Determination of the hemodynamics and histamine release of rocuronium (Org 9426) when administered in increased doses under N2O/O2-sufentanil anesthesia. Anesth Analg 1994;78:318-21. [PUBMED] |
|97.||Naguib M, Samarkandi AH, Bakhamees HS, Magboul MA, el-Bakry AK. Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine. Br J Anaesth 1995;75:588-92. [PUBMED] [FULLTEXT]|
|98.||Asuero MS, Larrodera L, Molins N, Rubial M, Dαvila P. Plasma histamine levels after the administration of atracurium or pancuronium in patients undergoing general anesthesia. Rev Esp Anestesiol Reanim 1992;39:341-4. |
Thomas M Hemmerling
Department of Anaesthesiology, Montreal General Hospital, 1650 Cedar Avenue, Montreal, H3G 1B7
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]
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