Laparoscopic Surgery and Muscle Relaxants

To the Editor: I have read the review by Kopman and Naguib1 with great interest! However, although comprehensively written by 2 of the most distinguished authors in their field, I dare to disagree with the format in which some of the studies are represented and with the review’s conclusions. I will confine my detailed criticism to the 3 most relevant headings from the original review. NONLAPAROSCOPIC SURGERY: ARE RELAXANTS ALWAYS NECESSARY? The authors make the point that “lessons learned from general surgery have applicability to laparoscopic surgery as well.”1 The first reference discussed in detail is a study by Tammisto and Olkkola,2 which concludes that “as anesthesia deepened, less intense block was required.” In the context of volatile-based anesthesia, this is not surprising. However, I would like to draw attention to a quote from the same article2: “We conclude that there is a linear relationship between the end-tidal concentrations of enflurane and the degree of neuromuscular block … However, due to huge interindividual variation, certain ‘overdosing’ of neuromuscular blocking drugs is necessary to guarantee adequate muscle relaxation of abdominal muscles during all stages of upper abdominal surgery.” Depth of anesthesia therefore appears to be not sufficiently predictive to avoid unsatisfactory operating conditions. The discussion of the study also states that tightness of abdominal muscles might have gone unnoticed because surgeons only complained when surgical conditions were grossly unacceptable (i.e., coughing). Therefore, I agree with the review’s authors that lessons can be learned from this study; however, my conclusion would be that depth of anesthesia is an unreliable predictor of surgical working conditions. It may also be mentioned that in the light of ongoing intense (and admittedly controversial) research into the possible side effects of “too deep” anesthesia, mentioning deep anesthesia as an easy way to improve surgical conditions may be seen as somewhat counterintuitive. In the review article, the authors also quote an investigation by King et al.3 as stating that 70% of patients did not require a neuromuscular-blocking agent to achieve good or excellent operating conditions. In response, I will highlight another statement by King et al.3: “Nonetheless, vecuronium significantly increased the proportion of patients in whom at least adequate (# grade 3) surgical field ratings were maintained throughout the procedure, from 72% (placebo group) to 98%.” In my view, at least this significantly changes the representation of the study, because it implies the question of whether nonadequate surgical conditions can and should really be tolerated in 30% of patients. DOES DEEP NEUROMUSCULAR BLOCK PROVIDE BETTER LAPAROSCOPIC SURGICAL CONDITIONS THAN MODERATE LEVELS OF BLOCK? Kopman and Naguib1 commence this section by quoting the study by Chassard et al.4 as finding no differences in surgical conditions in patients receiving either a neuromuscular-blocking agent to a twitch depression of 10% of control or no blocking drugs. According to a previous article by Kopman et al.5 as well as the authors’ definition of block levels in their review, this constitutes at best a “moderate versus no block study” and may hence be misplaced in the section of the review. Another larger study by Chen et al.6 is quoted in the same context. Although the review acknowledges many of the shortcomings of this article (i.e., no depth of block monitored), it quotes that “Satisfactory conditions for ventilation and operation were consistently achieved with and without muscle relaxants…”1 The readers should know that this study makes no mention of a standardized assessment of surgical working conditions. Are “satisfactory” conditions optimal or even “good”? The latter remains speculative. Two further articles7,8 referenced in the same context investigated paralyzed versus nonparalyzed patients. In both studies, nonparalyzed patients were allowed to breathe spontaneously throughout the procedure. However, in the trial by Williams et al.,8 pneumoperitoneum was rated as inadequate for trochar insertion in 5 of 18 (28%) patients (versus adequate in 100% of the paralyzed patients). Although the latter is acknowledged in the review, the review speculates whether this may have been the result of the fact that the nonparalyzed patients were breathing spontaneously and conclude that this may be a suboptimal technique for laparoscopic surgery.1 Would the lack of neuromuscular block not provide an alternative and perhaps even more likely explanation for unsatisfactory surgical conditions? A study by Paek et al.9 is quoted as “more universally applicable” in the argument against a significant benefit of deep block. In this study, patients received either no additional rocuronium (allowed to recover from the induction dose of 0.6 mg/kg) or incremental bolus doses to maintain a train-of-four (TOF) of 2 twitches. The authors state that “there were no complaints from any of the participating surgeons.”9 Besides the fact that the latter may not qualify as a standardized assessment of operating conditions, it should be highlighted that the “paralyzed” group in this study received a mere average of an additional 24 mg of rocuronium during procedures lasting approximately 103 minutes. The nonparalyzed group also only experienced a recovery of 4/4 twitches after 72 minutes! Because of the large dose of rocuronium administered to patients in both groups on induction, this study may have ultimately compared 2 very similarly blocked groups for the larger part of the operation. Hence, the results could in fact be seen as universally applicable to demonstrate the benefits of (albeit moderate) muscle relaxation. I completely agree with the authors that well-designed trials comparing deep with moderate block are rare if not nonexistent. However, the review quotes 3 studies,10–12 which at least attempt to provide such a comparison. First mentioned in the review is a trial by Martini et al.10 comparing surgical working conditions on a well-defined 5-point scale under conditions of either moderate (TOF 1–2) or deep (post tetatic count [PTC] 1–2) neuromuscular block. The review mentions that the mean difference of 0.7 points (4 vs 4.7 points) on the 1 to 5 scale had been, although statistically significant, relatively small. However, it is worth noting that this 18% difference was rated as “important and clinically significant” by the participating surgeons.10 Although this merely constitutes subjective opinion and not patient outcome, it should probably not be completely ignored. Furthermore, I would like to bring to attention that in this study, deep block resulted in 67% excellent surgical ratings, with moderate block, and this was found in only 34%. Despite this, conditions were rated “good” (“…a wide laparoscopic working field with sporadic muscle contractions, movements, or both”)10 in >80% of patients in the moderate-block group. However, although sporadic muscle contractions or movements may not prevent successful and safe surgery in many instances, it may be permitted to ask the question whether we can or should accept suboptimal surgical conditions in 2 of 3 patients when possibly dealing with higher risk procedures (i.e., robotic surgery). The same question applies when reading about the number of treatment failures (unacceptable surgical conditions; n = 14) reported by Dubois et al.11 in patients in their shallow block group. It is of course correct that Kopman and Naguib point out that the depth of block in this group might have been outside the definition of a moderate block. However, it is still interesting that at least half of these events were recorded either before the recovery of 4 twitches (n = 3) or at least at relatively low TOF ratios (<40%; n = 4). Ultimately, this may be close to what the intention to maintain moderate block might produce in clinical reality. Although I also agree with the review that some deep block patients were found paralyzed at more shallow levels (hence possibly better defined as moderate blocks), no treatment failure was reported at a TOF ≤1. Even when accepting that deep block in this study may have better been replaced with a moderate but a continuously monitored and maintained block, one can still conclude that allowing gradual recovery from deep to moderate neuromuscular block during laparoscopic surgery may result in undesirable operating conditions. CONCLUSIONS In their own conclusion, the authors of this review mention a study by De Jong13 as a noteworthy argument for a profound block to be unnecessary to achieve excellent surgical conditions. Although De Jong indeed found excellent conditions at the level of moderate block in most of his patients, his methodology for muscle relaxation (i.e., continuous succinylcholine administration) may have been appropriate in the 1960s but may fit the description of being awkward in today’s practice. Furthermore, it is left unclear whether and how the surgeons in this trial were blinded. As a matter of fact, the author never investigated whether a more profound block than the moderate block used in the study could have improved surgical conditions even more. In view of the findings by De Jong of increasing numbers of excellent ratings with increasing depth of neuromuscular block, one could at least hypothesize that this might have been the case. Finally, the review concludes that “Current practice in the United States where sugammadex is not available and deep block is not routinely practiced for laparoscopic surgery suggests that there is no pressing need to change current clinical routines.”1 In my view, this circulus in probando is difficult to accept as the final word of this review. Current practice in the United States alone can certainly not explain why there is currently no need to change clinical practice. Only data from well-conducted trials could, but this is ultimately still missing. Therefore, I fully agree that we have not yet seen sufficiently well-designed studies to recommend an optimum level of neuromuscular block. However, in the meantime, and based on reviewing Kopman and Naguib’s references in a slightly different light and as outlined earlier, I would personally adopt a slightly different conclusion. I may also refer to a recently published very balanced review about muscle relaxation in abdominal and gynecological surgery in my support.14 There is strong evidence that muscle relaxation per se improves laparoscopic surgical working conditions. Although a deep (versus moderate) block may theoretically be beneficial, well-designed trials have yet to establish a correlation with improved patient outcome. Thus, currently, there is no hard evidence to generally recommend a specifically deep neuromuscular block. However, maintenance of deep to moderate neuromuscular block (versus a one-off dose of a muscle relaxant on induction of anesthesia) throughout surgery seems to avoid undesirable surgical conditions. On first sight, this seems more feasible than it may actually be. With neostigmine-based reversal having just recently been (re-)confirmed to be problematic,15,16 anesthesiologists without unhindered access to sugammadex may find even the maintenance of moderate block during laparoscopic surgery challenging. In this context, careful—ideally quantitative—neuromuscular monitoring is a crucial component of relaxant anesthesia. Because sugammadex is not yet available in the United States, I fully agree with Kopman and Naguib that at this point in time, a change of practice cannot, therefore, be recommended. However, where neuromuscular monitoring is applied and where sugammadex is available, I would invite coworkers to experiment with deeper levels of block to gain their own experience and, by performing aforementioned missing studies, add to the scientific knowledge base of our specialty. Thomas Ledowski, MD, PhD School of Medicine and Pharmacology University of Western Australia Perth, Australia [email protected]