More Muscle Relaxation Does Not Necessarily Mean Better Surgeons or “The Problem of Muscle Relaxation in Surgery”

The role of the anesthesiologist in the operating room is to make surgery possible by making the experience acceptable to the patient and by providing suitable conditions for the surgeon to perform the procedure. These goals have not changed since the middle of the last century, when, in an article entitled “The Problem of Muscle Relaxation in Surgery,” Harold Griffith stated that the “duty of the modern anaesthesiologist” consisted of: “1. The safety of the patient before, during and after operation. 2. The comfort of the patient. 3. Provision of the best possible working conditions for the surgeon.”1 The drugs and techniques we use today, as in 1947, provide analgesia, sedation, and unconsciousness as mandated by the clinical situation and also should allow the surgeon to complete the procedure under suitable conditions. To achieve this goal, neuromuscular blocking agents are administered in many situations, and for certain procedures, surgeons often request optimal muscle relaxation. Traditionally, the optimal depth of neuromuscular blockade during general anesthesia has been a compromise between immobility during the procedure and complete recovery at the end of the operation. Even when assisted by anticholinesterase agents, recovery is slow and incomplete, so muscle relaxation must be managed in such a way as to allow sufficient spontaneous recovery by the end of the procedure.2 Airway protection and avoidance of respiratory complications postoperatively rely, in part, on intact pharyngeal function and on coordination between breathing and swallowing, particularly in the elderly.3 There is general consensus about the minimum acceptable target for recovery: a train-of-four (TOF) ratio of 0.9 should be obtained before neuromuscular function is considered adequate and tracheal extubation can be performed safely and reliably.2,4 However, surprisingly, there have been few studies on how much relaxation is needed during surgery. The study by Staehr-Rye et al.5 in this issue of Anesthesia & Analgesia was designed to address this knowledge gap. Our experience derived from daily work in the operating room suggests that the degree of muscle relaxation required depends on the surgical procedure, the patient, the depth of anesthesia, and the skill of the surgeon. One of the first attempts to estimate the degree of relaxation needed was made in 1966 by de Jong,6 who tested single twitch amplitude against surgical conditions as assessed by the surgeon. In 25 unspecified procedures, surgeons rated abdominal relaxation as “poor” in 17 instances, “adequate” in 3 other occasions, and never “excellent” when single twitch height was 71%–100% of control. When twitch height was 1%–25% of control, the ratings were never “poor”; they were rated as “adequate” in 4 instances and “excellent” 21 times. This investigation was performed before the introduction of the TOF mode of stimulation, which appeared in the early 1970s,7 and subsequent investigators interpreted de Jong’s findings in terms of TOF response.8 When the first twitch height is 1%–25% of control, only 1 or 2 visible TOF twitches are present. Surprisingly, de Jong’s work, which was not randomized, not blinded, and limited to 25 patients with statistical methods below modern standards, has never been repeated or validated. Perhaps the most significant attempt at defining the role of neuromuscular blocking agents in surgery was the randomized, controlled, blinded study on the requirement for vecuronium in prostatectomy by King et al.9 The question was not which level of blockade corresponded to adequate surgical conditions, but whether vecuronium was better than placebo. The vecuronium dose was adjusted to keep the TOF count at 0 or 1 visible twitches. All patients received a generous dose of isoflurane (>1 MAC), and hyperventilation (end-tidal carbon dioxide of 26–27 mm Hg) was applied to suppress respiratory drive. Surgical field rating was scored on a 1–4 scale. Essentially, use of vecuronium virtually eliminated grade 4 ratings (unacceptable) present in approximately 25% of placebo patients and increased the proportion of grade 1 ratings (excellent) by the same proportion. The authors recognized that muscle relaxation may not be needed in every case and concluded by recommending an “à la carte” approach, which involved giving neuromuscular blocking agents only when appropriate. Lighter levels of anesthesia and normocapnia could have produced a greater need for neuromuscular blockade. The paradigm has changed in recent years with the development of more complex laparoscopic procedures in a population that tends to be increasingly heavier. Such operations are perceived as requiring immobility and, therefore, a high degree of muscle relaxation. The opportunity for almost limitless neuromuscular blockade has also emerged because of the ability of sugammadex to antagonize rocuronium blockade at any level of paralysis.10 This means that, at least in the countries where sugammadex is available (this list excludes the United States and Canada), it is possible to continue deep blockade right up to the very end of the surgical procedure. However, before such a technique involving large doses of rocuronium followed by large doses of sugammadex can be recommended, the usefulness of maintaining deep blockade until “the last stitch” needs to be documented. This is why Staehr-Rye et al. designed their study and why their results are noteworthy. Patients were randomized to deep (posttetanic count [PTC] of 0–1) or moderate (at least 1 twitch to TOF stimulation) blockade.5 However, whereas the deep group received top-up doses of rocuronium, the moderate blockade group did not receive any more rocuronium, and many of these patients had very shallow blockade, if any, toward the end of surgery. In fact, the Staehr-Rye et al. study compared deep blockade with almost no blockade at all. The surgical procedure chosen was laparoscopic cholecystectomy, and the surgeons decided to add another level of complexity. Instead of performing the case at a standard pneumoperitoneum pressure of 15 mm Hg, they attempted to operate at only 8 mm Hg, thus making the operation potentially more difficult. Moreover, the 2 participating surgeons were “not familiar with low-pressure laparoscopic surgery” when the study was initiated. Therefore, the situation may be considered a “worst-case scenario”: if no difference could be seen in these rather adverse conditions, then it is likely that no effect would be observed in “normal” conditions that include a pneumoperitoneum insufflation pressure of 15 mm Hg. The choice of this particular design illustrates the intimate relationship between emerging anesthesia techniques and surgery. If neuromuscular blocking agents had not been available, the drive to perform increasingly complex laparoscopic surgery would have been blunted considerably, and the idea of performing such procedures at a low pneumoperitoneum pressure would probably not have emerged. Claims have been made that low-pressure laparoscopy is associated with less postoperative pain, more hemodynamic stability, and fewer adverse effects on pulmonary function.11 If this surgical technique is deemed desirable for patients, then the anesthetic should be appropriately fine-tuned to create optimal operating conditions. However, we must take a step back and ask 2 separate but highly related questions: First, what is the effect of intra-abdominal pressure (standard versus low) on surgical conditions at identical depths of neuromuscular blockade? Second, what is the effect of the depth of neuromuscular blockade (deep versus shallow) on surgical conditions at identical intra-abdominal insufflation pressure? Once we have these answers, perhaps we could attempt to determine whether both low-pressure pneumoperitoneum and deep neuromuscular block result in optimal surgical conditions and improved patient outcomes. The primary outcome in the Staehr-Rye et al. study was the proportion of procedures that could be completed under optimal conditions at a (low) pressure of 8 mm Hg. Even with deep blockade, only 60% of the procedures met this criterion; with moderate blockade, only 35% of cases were completed at low pressure, an absolute difference of 25%. However, because this was a small study (n = 48 patients), the difference was not statistically significant. Conditions were judged “optimal” by the surgeon in only 28% in the deep blockade group and 4% in the moderate group, a difference that was marginally statistically significant. It is interesting to note that the magnitude of the difference was similar to that found in the prostatectomy study by King et al. (8), around 25%. Muscle relaxation played a role in only a fraction of surgeries, and the situation was judged suboptimal in nearly three-quarters of cases, even with deep blockade. The situation might improve as surgeons gain experience, but clearly neuromuscular blockade alone cannot make surgical conditions optimal in all, even in most, cases. Two other recent attempts have been made to explore the role of neuromuscular blockade in complex laparoscopic procedures but with standard intraperitoneal pressures. With deep (PTC: 1–2) blockade, Martini et al.12 found 35% more patients with optimal surgical conditions and 18% more with good to optimal conditions, compared with moderate blockade (TOF count: 1–2). Dubois et al.13 randomized laparoscopic hysterectomy patients to either shallow or deep block and also found 26% more optimal conditions with deep blockade (TOF twitch count of <1) than with shallow blockade (spontaneous recovery was allowed). There was also an inverse relationship between twitch count and probability of optimal conditions. Taken together, these studies support the notion that depth of neuromuscular blockade makes a difference in approximately one-quarter of cases, without identifying which patients are most likely to benefit or how deep the level of block needs to be in those individuals. Multiple costs are associated with keeping neuromuscular blockade deep until the end of the surgical procedure. Either large doses of sugammadex (4 mg/kg at a PTC of 1–2) are required or approximately $200 per patient where the drug is available. The alternative is to mechanically ventilate the lungs until 4 twitch responses return, and then pharmacologic antagonism with neostigmine can be attempted.4 This delay also carries a cost, either as time wasted in the operating room14 or prolonged stay in the postanesthesia care unit.15 In this study,5 we have some evidence that deep neuromuscular blockade makes a difference in some cases, but the experience is limited to 2 surgeons and 1 type of procedure performed at a pneumoperitoneal pressure of 8 mm Hg, which is not the current surgical standard. More evidence of the real benefit of keeping patients deeply paralyzed until the end of surgery needs to be provided before this practice can be recommended, regardless of whether sugammadex is available. Additionally, the influence of insufflation intraabdominal pressure (low versus standard) needs to be defined prospectively, given the equivocal data on the purported benefits of the low-pressure surgical techniques.11 Perhaps the words of the now-famous Harold R. Griffith are still applicable today: “The best surgeon is the one who handles tissues gently, does it quickly, and gets out of the abdomen or chest with no time wasted in ‘puttering’. The expert should not need ‘wet rag relaxation’ for every laparotomy.”1 RECUSE NOTE Dr. Sorin J. Brull is the Section Editor for Patient Safety for the journal. This manuscript was handled by Dr. Peter Glass, Section Editor for Ambulatory Anesthesia, and Dr. Brull was not involved in any way with the editorial process or decision. DISCLOSURES Name: François Donati, PhD, MD. Contribution: This author helped write the manuscript. Attestation: François Donati approved the final manuscript. Conflicts of Interest: This author has no conflicts of interest to declare. Name: Sorin J. Brull, MD, FCARCSI (Hon.). Contribution: This author helped write the manuscript. Attestation: Sorin J. Brull approved the final manuscript. Conflicts of Interest: Sorin J. Brull has been a consultant for Merck & Co.

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