Background

The number of trials investigating the effects of deep neuromuscular blockade (NMB) on surgical conditions and patient outcomes is steadily increasing. Consensus on which surgical procedures benefit from deep NMB (a posttetanic count [PTC] of 1 to 2) and how to implement it has not been reached. The European Society of Anaesthesiology and Intensive Care does not advise routine application but recommends use of deep NMB to improve surgical conditions on indication. This study investigates the optimal dosing strategy to reach and maintain adequate deep NMB during total intravenous anesthesia.

Methods

Data from three trials investigating deep NMB during laparoscopic surgery with total intravenous anesthesia (n = 424) were pooled to analyze the required rocuronium dose, when to start continuous infusion, and how to adjust. The resulting algorithm was validated (n = 32) and compared to the success rate in ongoing studies in which the algorithm was not used (n = 180).

Results

The mean rocuronium dose based on actual bodyweight for PTC 1 to 2 was (mean ± SD) 1.0 ± 0.27 mg · kg−1 ·h−1 in the trials, in which mean duration of surgery was 116 min. An induction dose of 0.6 mg ·kg−1 led to a PTC of 1 to 5 in a quarter of patients after a mean of 11 min. The remaining patients were equally divided over too shallow (additional bolus and direct start of continuous infusion) or too deep; a 15-min wait after PTC of 0 for return of PTC to 1 or higher. Using the proposed algorithm, a mean 76% of all 5-min measurements throughout surgery were on target PTC 1 to 2 in the validation cohort. The algorithm performed significantly better than anesthesiology residents without the algorithm, even after a learning curve from 0 to 20 patients (42% on target, P ≤ 0.001, Cohen’s d = 1.4 [95% CI, 0.9 to 1.8]) to 81 to 100 patients (61% on target, P ≤ 0.05, Cohen’s d = 0.7 [95% CI, 0.1 to 1.2]).

Conclusions

This study proposes a dosing algorithm for deep NMB with rocuronium in patients receiving total intravenous anesthesia.

Editor’s Perspective
What We Already Know about This Topic
  • Deep neuromuscular blockade may be required for the safe execution of some surgeries

  • The optimal dosing strategy to reliably achieve deep neuromuscular blockade has not been defined

What This Article Tells Us That Is New
  • Application of a proposed practical dosing algorithm enabled the optimal level of deep neuromuscular blockade to be achieved in over three quarters of patients.

  • Use of the algorithm significantly increased the achievement of the target level of neuromuscular blockade compared to when clinical judgment alone was used.

The number of trials investigating the effects of deep neuromuscular blockade (NMB) during surgery on surgical conditions and patient outcomes is steadily growing.1–4  Nonetheless, consensus on which surgical procedures benefit from deep NMB and especially how to implement it has not been reached. Trials with comparable study protocols reveal conflicting outcomes. More noteworthy and concerning is that many trials publish results without neuromuscular monitoring data, rocuronium dose, or description of how well they succeeded in reaching the intended level of blockade. Moreover, there is considerable variability in reported doses between articles aiming for the same level of NMB. The 2017 AQUILES consensus study5  assembled a large panel of anesthesiologists and surgeons to establish expert recommendations on the use of deep NMB in clinical practice. Expert opinion was nearly unanimous in the belief that deep NMB is highly suitable in abdominal surgery (94.1%), and more than 80% of the panelists agreed on the need for consensus protocols applicable to both surgeons and anesthesiologists. The European Society of Anaesthesiology and Intensive Care reports insufficient evidence for routine application of deep NMB but recommends it can be used to improve surgical conditions when needed.6  Poor surgical conditions are associated with a higher incidence of surgical complications.7  In our experience, achieving and maintaining an adequate deep neuromuscular block (a posttetanic count [PTC] of 1 to 28 ) throughout surgery can prove challenging even for experienced anesthesiologists. It requires frequent monitoring, even more so because the potency and pharmacokinetics of neuromuscular blocking agents (NMBAs) like rocuronium can be influenced by many factors such as age,9  body mass index,10  race,11  or the type of anesthetic used,12,13  and no clear-cut dosing guidelines exist. Therefore, a practical dosing algorithm that can easily be applied when there is an indication for deep NMB will likely aid clinicians to reach the desired level of NMB more quickly and accurately.

To investigate the optimal dosing strategy to reach and maintain adequate deep NMB throughout surgery under total intravenous anesthesia, we have pooled data from our previous randomized clinical trials investigating deep NMB. In this article, we aim to develop a practical clinical dosing algorithm that can be used to induce and maintain deep NMB throughout surgery.

The algorithm was developed in three steps: (1) determination of the ideal induction dose and total dose in mg · kg−1 · h−1 based on actual bodyweight, (2) determination of when to start continuous infusion and how to adjust, and (3) validation of the resulting algorithm with a comparison to the success rate without the algorithm (fig. 1). For step 1, we pooled neuromuscular monitoring data from the RELAX study (clinicaltrials.gov NCT02838134; n = 96) investigating deep versus moderate NMB in laparoscopic donor nephrectomy14  and the BLISS trial (trialregister.nl NTR5380; n = 150) comparing deep with moderate NMB or a single-shot intubation dose of rocuronium during bariatric surgery,15  to determine the appropriate induction dose and total dose in mg · kg−1 · h−1. In both trials, patients received total intravenous anesthesia (TIVA) with propofol and remifentanil, and NMB was induced and, where applicable, maintained with rocuronium. Monitoring was performed with the TOF-watch-SX monitor, with measurements every 5 min for the RELAX study and every 10 min during the BLISS study. This information was incorporated for the RECOVER study (clinicaltrials.gov NCT03608436), comparing deep versus moderate NMB in patients undergoing laparoscopic colorectal surgery (n = 178) with TIVA and rocuronium.16  NMB measurements were performed every 5 min with the train-of-four (TOF) scan.17  The automatic TOF–PTC (ATP) function was used, which means the TOF scan measures a TOF count, and when the TOF count is 0, a PTC is automatically measured. This circle is repeated every 5 min. The induction dose and total dose determined in step 1 were used in step 2, during which the times to start continuous infusion and adjustments or additional boluses were explored. The resulting concept algorithm was validated in 12 patients in the HIPPO study (clinicaltrials.gov NCT05562999) in patients undergoing total hip replacement surgery with TIVA and an additional 20 patients undergoing laparoscopic colorectal surgery during implementation of the algorithm in our hospital. NMB measurements were also performed every 5 min with the TOF Scan. This validation cohort was compared to patients from the ongoing EURO-RELAX (clinicaltrials.gov NCT04124757), RECOVER-2 (NCT04250883), and HIPPO18  studies (total n = 180), in which the algorithm was not used.

Fig. 1.

Study design. BLISS study15 , HIPPO study18 , RECOVER study16 , RELAX study14 . PTC, posttetanic count.

Fig. 1.

Study design. BLISS study15 , HIPPO study18 , RECOVER study16 , RELAX study14 . PTC, posttetanic count.

Close modal

Total Dose and Induction Dose

In step 1, individual NMB measurements of each patient were classified as intense (PTC 0), deep (PTC 1 to 2), deep to moderate (PTC 3 to 10), moderate (TOF count of 1 to 2), or shallow (TOF count of 3 to 4; table 1). Patients were grouped based on the percentage of NMB measurements in each category throughout the surgery. Patients were assigned to a group when 75% or more of the measurements were in the same category or to an in-between category (I, II, III or IV) when 75% or more of the measurements were divided over two categories (table 1). Patients that could not clearly be categorized due to a large variability in measurements were excluded from analysis. Duration of surgery was defined as the time from first incision until closing of the wound was finished. For patients who received a single shot of rocuronium (or for cases in which continuous infusion or additional boluses were not administered until later), the attained depth of NMB and duration until recovery was analyzed. An intubation dose of 0.3 (range, 0.2 to 0.4) mg/kg was compared with an intubation dose of 0.6 (range, 0.5 to 0.7) mg/kg. The rocuronium dose was reported as mean ± SD.

Table 1.

NMB Measurements from the RELAX and BLISS Studies

NMB Measurements from the RELAX and BLISS Studies
NMB Measurements from the RELAX and BLISS Studies

When to Start Continuous Infusion and How to Adjust

The induction dose and total dose found in step 1 were applied in step 2, during which the lowest TOF count or PTC and time to reach this count after the standardized induction dose were determined. An explorative analysis of the effect of additional boluses or adjustment of continuous infusion was performed by identifying the corresponding increase in NMB depth.

Algorithm Validation

To evaluate the accuracy of the algorithm to achieve and maintain deep NMB, we compare the performance (defined as the percentage of measurements that are on target PTC 1 to 2) of four dedicated researchers (anesthesiology residents only adjusting the NMB level during the EURO-RELAX, RECOVER-2, and HIPPO study and not otherwise involved in patient care) to the performance when two of these researchers strictly follow the algorithm in the same patient category. To investigate whether a learning curve is present in the performance of the individual residents, the results are split into groups of 20 consecutive patients. The percentage of measurements from induction until the end of surgery that are on target PTC 1 to 2 with and without use of the algorithm are compared with a Student’s t test, and a P value < 0.05 is considered statistically significant. Cohen’s d is used to estimate the effect size.

Statistical Analysis and Graphics

The analyses were performed in IBM SPSS Statistics, version 27. Images were made with GraphPad PRISM version 919  and Lucidchart.20 

The baseline, surgery, and anesthesia characteristics for the RELAX, BLISS, and RECOVER study are displayed in table 2.

Table 2.

Patient and Surgery Characteristics

Patient and Surgery Characteristics
Patient and Surgery Characteristics

Step 1. Rocuronium Dose–Response

Neuromuscular monitoring data were available for 239 of 246 patients. For the RELAX study (patients undergoing laparoscopic donor nephrectomy), the mean duration of surgery was 146 ± 38 min; an average of 19 NMB measurements per patient were used in the analysis. Mean duration of surgery in the BLISS study (patients undergoing bariatric surgery) was 46 ± 15 min, with an average of 6 NMB measurements per patient included in the analysis. All patients received total intravenous anesthesia with propofol and remifentanil. Table 3 shows the number of patients in each monitoring category: intense (PTC 0), deep (PTC 1 to 2), deep to moderate (PTC 3 to 10), moderate (TOF count of 1 to 2), and shallow NMB (TOF count of 3 to 4). More than 75% of measurements were in one category for 131 patients, for 92 patients more than 75% of measurements were divided over two categories, they were assigned to in-between categories I, II, III, or IV (table 1). Eleven patients for whom measurements were divided over three categories were assigned to the best-fitting category; for example, 31% PTC 0, 38% PTC 1 to 2, and 31% PTC 3 to 10 was assigned to the category PTC 1 to 2. Five patients could not be categorized; in four patients the majority of measurements were TOF count 0, and no PTC was measured, and for one patient, the measurements were divided between four categories. Figure 2 displays the mean dose of rocuronium in mg · kg−1 · h−1 for actual bodyweight. For deep NMB, the mean required dose was 1.0 ± 0.27 mg · kg−1 · h−1 (including the induction dose). Comparing spontaneous recovery of neuromuscular function after a single intubation dose of 0.3 mg/kg versus 0.6 mg/kg rocuronium in BLISS patients revealed that 10 min after administration of rocuronium, 75% of patients who received 0.6 mg/kg had a TOF count of 0, compared to 20% of patients who received 0.3 mg/kg. After 20 min, this decreased to 56% of patients with a TOF count 0 for 0.6 mg/kg and 5% TOF count 0 for 0.3 mg/kg.

Table 3.

Patient Monitoring Categories

Patient Monitoring Categories
Patient Monitoring Categories
Fig. 2.

Mean dose of rocuronium in mg · kg−1 ·h−1 for patients categorized based on neuromuscular monitoring. Categories on the x-axis are A (posttetanic count [PTC] 0 and in-between category I combined), PTC 1 to 2 (deep neuromuscular blockade [NMB]), B (category II, PTC 3 to 10 and category III combined), train of four (TOF) 1 to 2 (moderate NMB), C (category IV), and TOF 3 to 4 (shallow NMB; table 3).

Fig. 2.

Mean dose of rocuronium in mg · kg−1 ·h−1 for patients categorized based on neuromuscular monitoring. Categories on the x-axis are A (posttetanic count [PTC] 0 and in-between category I combined), PTC 1 to 2 (deep neuromuscular blockade [NMB]), B (category II, PTC 3 to 10 and category III combined), train of four (TOF) 1 to 2 (moderate NMB), C (category IV), and TOF 3 to 4 (shallow NMB; table 3).

Close modal

Step 2: Continuous Infusion and How to Adjust

An intubation dose of 0.6 mg/kg was consistently used in the deep NMB arm of the RECOVER trial. This allowed for identification of three response patterns as shown in figure 3: line A shows that NMB either remains too shallow and that additional intervention is required to reach PTC of 1 to 2; line B shows that NMB reaches a PTC 1 to 5 and that continuous infusion should be started at the right time to maintain deep NMB; and line C shows that PTC reaches 0 and that continuous infusion should be delayed until a PTC of 1 is observed. For 68 RECOVER patients receiving deep NMB, monitoring was sufficiently detailed to adequately determine the lowest measurement and time to reach the lowest measurement. Figure 3 shows that approximately a quarter of patients follow curve B and reach a PTC of 1 to 5 after a mean of 11 min after the induction dose of 0.6 mg/kg. The remaining 75% of patients are equally divided over response patterns A and C and need either an additional bolus and direct start of the continuous infusion or an approximate 15-min wait after PTC 0 before return of the PTC to at least 1, respectively.

Fig. 3.

Distribution of RELAX14  and BLISS15  patients across the three possible response patterns for the initial decline of the train-of-four (TOF) count/posttetanic count (PTC) after the intubation dose of 0.6 mg/kg: (A) the level of neuromuscular blockade does not reach PTC 1 to 2 but remains too shallow; (B) PTC 1 to 2 is reached and requires the right timing to start continuous infusion; or (C) neuromuscular blockade (NMB) becomes too deep (PTC 0) for X amount of time before returning to PTC 1 or 2, and continuous infusion should be delayed until a PTC of 1 returns. The ranges show the fastest and slowest times to reach the lowest NMB measurement; for (A) and (B), continuous infusion can be started 12 min after the induction dose, whereas in the case of (C), continuous infusion needs to wait up to 25 min.

Fig. 3.

Distribution of RELAX14  and BLISS15  patients across the three possible response patterns for the initial decline of the train-of-four (TOF) count/posttetanic count (PTC) after the intubation dose of 0.6 mg/kg: (A) the level of neuromuscular blockade does not reach PTC 1 to 2 but remains too shallow; (B) PTC 1 to 2 is reached and requires the right timing to start continuous infusion; or (C) neuromuscular blockade (NMB) becomes too deep (PTC 0) for X amount of time before returning to PTC 1 or 2, and continuous infusion should be delayed until a PTC of 1 returns. The ranges show the fastest and slowest times to reach the lowest NMB measurement; for (A) and (B), continuous infusion can be started 12 min after the induction dose, whereas in the case of (C), continuous infusion needs to wait up to 25 min.

Close modal

The effect of a bolus or infusion adjustment was difficult to isolate and compare, because they were often applied simultaneously or one shortly after the other and from a different NMB starting point. Nonetheless, scoring the individual responses generated a fair measure for an algorithm. Roughly, a bolus of 5 mg lowers the PTC by 2 to 3 counts, a bolus of 10 mg lowers the PTC by 4 to 6 counts, and a bolus of 15 mg lowers the PTC by 6 to 8 counts. A distinction was made between initial induction toward deep versus adjustments and re-evaluation later in the surgery. Over half of the RECOVER patients reached a stable phase during which no adjustments of the continuous infusion or additional boluses were needed (mean duration, 90 min; range, 30 to 205 min). During longer surgeries, the PTC tended to drop to 0 after this long stable phase with continuous infusion. This drop to PTC 0 occurred on average after 2.5 h (157 min; range, 92 to 227 min) and often required a strong dose reduction to return to PTC 1 to 2.

Step 3: Algorithm Validation

The concept algorithm was validated by two dedicated researchers (anesthesiology residents only adjusting the NMB level and not otherwise involved in patient care; R2 and R4 in fig. 4A) in 12 HIPPO trial patients and 20 colorectal surgery patients during implementation of the algorithm in our hospital, in whom we found a mean 76% of measurements (including the initial decline from TOF count 4 after induction) were on target PTC 1 to 2. The algorithm performed significantly better than four dedicated residents (R1, R2, R3, and R4 in fig. 4A) had done before without the algorithm (n = 180) after a learning curve of 0 to 20 patients (a mean 42% PTC 1 to 2, P ≤ 0.001, Cohen’s d = 1.4 [95% CI, 0.9 to 1.8]), 21 to 40 patients (a mean 37% PTC 1 to 2, P ≤ 0.001, Cohen’s d = 1.6 [95% CI, 1.0 to 2.1]), 41 to 60 patients (a mean 46% PTC 1 to 2, P ≤ 0.001, Cohen’s d = 1.5 [95% CI, 0.9 to 2.1]), 61 to 80 patients (a mean 43% PTC 1 to 2, P ≤ 0.001, Cohen’s d = 1.3 [95% CI, 0.7 to 1.9), and 81 to 100 patients (a mean 61% PTC 1 to 2, P ≤ 0.05, Cohen’s d = 0.7 [95% CI, 0.1 to 1.2]; fig. 4).

Fig. 4.

A comparison of the mean percentage of measurements on target posttetanic count (PTC) 1 to 2 with and without the algorithm (“ROCURITHM”). (A) Mean percentage of target PTC 1 to 2 of four dedicated researchers (anesthesiology residents). The x-axis denotes the number of consecutive patients. The algorithm was validated by researcher 2 (R2; HIPPO18 ) and R4 (implementation), who scored significantly better than without the algorithm. R1 and R3 did not use the algorithm, so no comparison could be made. (B) Aggregated data, the algorithm performed significantly better across the whole learning curve. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; NS, not significant.

Fig. 4.

A comparison of the mean percentage of measurements on target posttetanic count (PTC) 1 to 2 with and without the algorithm (“ROCURITHM”). (A) Mean percentage of target PTC 1 to 2 of four dedicated researchers (anesthesiology residents). The x-axis denotes the number of consecutive patients. The algorithm was validated by researcher 2 (R2; HIPPO18 ) and R4 (implementation), who scored significantly better than without the algorithm. R1 and R3 did not use the algorithm, so no comparison could be made. (B) Aggregated data, the algorithm performed significantly better across the whole learning curve. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; NS, not significant.

Close modal

The Algorithm

Figure 5 reveals the proposed algorithm for deep NMB (PTC 1 to 2) with rocuronium in patients receiving total intravenous anesthesia. Extrapolating the response patterns from figure 3 directs that the first assessment of NMB after stabilization 4 is likely approximately 10 min after the induction dose. Once continuous infusion is started, clinicians then reassess and act every one to three measurements based on the trend.

Fig. 5.

The rocuronium dosing algorithm for deep neuromuscular blockade (posttetanic count [PTC] 1 to 2). Bolus doses are marked as +5 mg, +10 mg, or +15 mg, whereas mg/h indicates an increase in continuous infusion. In the final step, the bolus and increase in continuous infusion are applied at the same time. Dose reductions may be considered when there is a marked disparity between actual and ideal bodyweight. NMB, neuromuscular blockade; TOF, train of four.

Fig. 5.

The rocuronium dosing algorithm for deep neuromuscular blockade (posttetanic count [PTC] 1 to 2). Bolus doses are marked as +5 mg, +10 mg, or +15 mg, whereas mg/h indicates an increase in continuous infusion. In the final step, the bolus and increase in continuous infusion are applied at the same time. Dose reductions may be considered when there is a marked disparity between actual and ideal bodyweight. NMB, neuromuscular blockade; TOF, train of four.

Close modal

In this article, we propose a practical dosing algorithm to induce and maintain deep NMB with rocuronium in patients receiving TIVA. In our validation cohort, 76% of the 5-min measurements were on target PTC 1 to 2. Although three quarters of measurements on target may not seem like a very high score, this includes the initial decline from TOF count 4 after induction. This takes about four or five measurements and has to be balanced by 12 (e.g., an hour) on target PTC 1 to 2 measurements to still reach 75%. In comparison, dedicated anesthesiology residents only reach a mean 40 to 60% on target PTC 1 to 2 without the algorithm. Of course, the question remains whether this small target range is absolutely necessary. Why deep NMB should be a PTC of 1 to 2 measured at the adductor pollicis muscle is outlined in the latest NMB classification article8 ; it is the deepest but still quantifiable NMB that can be achieved. At PTC 0, the exact NMB depth is unknown, and we cannot estimate the time to recovery or the required dose of sugammadex to avoid residual blockade. Recovery of function at the diaphragm precedes recovery at the m. adductor pollicis and at a PTC of 1, diaphragmatic activity is already at 10% of control. At a PTC of 5 or less, activity is at 21% of control,21  which means that at higher PTC levels, contraction of the abdominal muscles may impede the surgical field. The algorithm provides a relatively easy way to remain within this range. This is supported by the validation in which anesthesiology residents who use the algorithm have more on target measurements than those who do not use the algorithm. Especially in the beginning of the learning curve, the effect size of the algorithm is large. Although there can be significant clinical variation in applying deep NMB both without the algorithm (e.g., experienced clinicians who do this often) and with the algorithm (there is room for interpretation, for example in “reassess and act every one to three measurements”), the aggregated scores of four residents in a total of 180 patients minimize the chances of seeing a resident-specific effect (for example, a young resident who has little experience in dosing for deep NMB but performs well with the algorithm). Figure 4A shows the separate scores for each resident, which supports that for the first 20 patients there are no major differences between residents. Some residents may show a faster learning curve than others, and experienced anesthesiologists may not need the help, but as long as deep NMB is not routinely applied in clinical practice, many clinicians will remain in the early stages of their learning curve where the algorithm could prove helpful.

The proposed algorithm and doses are in line with previous pharmacokinetic and pharmacodynamic models and dose finding studies of rocuronium.22,23  The limitations of this study mainly pertain to generalizability, because it is well known that NMBAs and in particular rocuronium have a large variability in onset and recovery. Although the algorithm was developed with different types of surgery, in both sexes, and with a broad range of ages and body mass indexes, it may not be as precise for all patients or types of surgery. The algorithm was developed with doses based on actual bodyweight. Particular consideration was given to the most appropriate weight metric for dosing in obese patients. Our algorithm was mainly informed by trials in which actual and ideal body weights were comparable, with an additional trial specifically involving obese bariatric surgery patients. Although Meyhoff et al.24  suggest that dosing based on ideal or corrected body weight may be preferable in such populations to avoid overdosing, our investigations into an ideal bodyweight–based strategy did not result in a more accurate dose–response relationship. Nonetheless, dose reductions may be considered when there is a marked disparity between actual and ideal bodyweight. In addition, it is important to keep in mind other influencing factors like age, renal function, race, and use of anesthetics and adjuncts like magnesium.25  Nevertheless, the algorithm allows for continuous adjustment when the NMB is too shallow or too deep.

Finally, the monitoring technique is important to consider when using the algorithm. The algorithm was developed with the TOF Watch SX and TOF Scan. the TOF Watch SX measures NMB by acceleromyography, and the TOF Scan measures with 3D acceleromyography. These two methods/appliances have a good agreement.26  Acceleromyography (AMG) and electromyography are the most commonly used quantitative monitoring techniques in clinical practice. Both techniques can “under read,” where twitches can be seen or palpated that are not registered on the monitor.27,28  Moreover, set-up of each individual monitor (stabilization, normalization, or use of preload) can lead to a delay or influence measurements.29  For example, the TOF scan uses a default current of 50 mA, but more may be needed for obese patients, for whom the distance between the electrodes and ulnar nerve is greater, leaving them at risk of not receiving a supramaximal current. The STIMPOD NMS 450X has integrated both AMG and electromyography into one device and allows for choosing of the most optimal technique based on the clinical setting, for example whether the arms of the patient need to be tucked in during surgery.30  Evidence-based principles for different neuromuscular monitoring techniques in clinical practice have recently been comprehensively summarized in BJA Education.31  It is advisable for clinicians to familiarize themselves with the specifics of their monitoring technique of choice (and in relation to AMG) for optimal and reliable interpretation of measurements. Ideally in the future, the algorithm will be programmed into a closed-loop system, which was already developed for rocuronium with continuous NMB monitoring.32,33  In the meantime, the algorithm can relatively easily be applied in clinical practice without the need for new devices or software. The algorithm was developed from surgeries with a mean duration of 2 h; it is anticipated that surgeries extending well beyond this time frame may necessitate decreased dosages as they progress, and the final step of the algorithm allows for this reassessment and titration.

The algorithm was developed for use during TIVA as the benefits of deep NMB for surgical conditions during volatile anesthesia seem to be limited, which can be explained by spinal inhibition of motor neuron excitability and peripheral augmentation of NMBA potency at the neuromuscular junction by inhalational anesthetics.34  Although there is currently insufficient evidence for routine use of deep NMB, the nearly complete international randomized controlled EURO-RELAX trial (clinicaltrials.gov NCT04124757) investigating intraoperative safety of moderate versus deep NMB during laparoscopic surgery at standard intra-abdominal pressure will provide more answers.

Although immediate monitoring and algorithm application after induction are ideal, we recognize that airway management, hemodynamic stability, and patient positioning take precedence. In cases in which NMB has partially recovered before the application of the algorithm, an additional rocuronium bolus can be considered. Optimal conditions would allow for unobstructed observation of hand movement during surgery to ensure accurate measurements. During potential disruptions such as table motions or diathermy, it can be helpful to assess the consistency of observed NMB measurements with the expected clinical response after a given dose. Monitoring should always be applied with the use of NMBAs.35  Upon completion of surgery, we recommend following international guidelines for monitoring and reversal to prevent residual NMB.6,36 

In conclusion, we have devised an algorithm designed to induce and maintain deep NMB during total intravenous anesthesia. This algorithm offers a structured approach that can be integrated into clinical practice. It represents a convergence of pharmacokinetic and pharmacodynamic principles with clinical operability, aiming to facilitate the precise management of deep NMB during surgery.

Research Support

Supported by Merck Sharp & Dohme (Rahway, New Jersey; to Dr. Michiel Warlé and Dr. Dahan).

Competing Interests

Merck Sharp & Dohme was in no way involved in conceptualization, development of the algorithm, writing, or any other aspect of this article. The opinions presented here are those of the authors and do not represent the opinion of Merck Sharp & Dohme or any of its partners. In addition, Dr. Dahan reports financial relationships with Enalare (Princeton, New Jersey) and Trevena (Chesterbrook, Pennsylvania), and grants from the Food and Drug Administration (Bethesda, Maryland) and ZonMw (The Hague, The Netherlands). The other authors declare no competing interests.

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