Perioperative Medicine

ABSTRACT
Background: The number of trials investigating the effects of deep neu-
romuscular blockade (NMB) on surgical conditions and patient outcomes is

A Practical Dosing 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

Algorithm for Deep

not been reached. The European Society of Anaesthesiology and Intensive
Care does not advise routine application but recommends use of deep NMB

Neuromuscular Blockade
to improve surgical conditions on indication. This study investigates the opti-
mal dosing strategy to reach and maintain adequate deep NMB during total
intravenous anesthesia.
during Total Intravenous

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Methods: Data from three trials investigating deep NMB during laparoscopic

Anesthesia: ROCURITHM 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
Kim I. Albers-Warlé, M.D., success rate in ongoing studies in which the algorithm was not used (n = 180).
Gabby T. J. A. Reijnders-Boerboom, M.D., Veerle Bijkerk, M.D.,
Bart Torensma, Ph.D., Ivo F. Panhuizen, M.D., Ph.D., Results: The mean rocuronium dose based on actual bodyweight for PTC 1
Marc M. J. Snoeck, M.D., Ph.D., 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
Thomas Fuchs-Buder, M.D., Ph.D., Christiaan Keijzer, M.D., Ph.D.,
PTC of 1 to 5 in a quarter of patients after a mean of 11 min. The remaining
Albert Dahan, M.D., Ph.D.,
patients were equally divided over too shallow (additional bolus and direct
Michiel C. Warlé, M.D., Ph.D.
start of continuous infusion) or too deep; a 15-min wait after PTC of 0 for
Anesthesiology 2024; 141:365–74 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 anesthe-
siology residents without the algorithm, even after a learning curve from 0
EDITOR’S PERSPECTIVE 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%
What We Already Know about This Topic
CI, 0.1 to 1.2]).
• Deep neuromuscular blockade may be required for the safe execu-
tion of some surgeries Conclusions: This study proposes a dosing algorithm for deep NMB with
• The optimal dosing strategy to reliably achieve deep neuromuscular rocuronium in patients receiving total intravenous anesthesia.
blockade has not been defined (Anesthesiology 2024; 141:365–74)

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
T he number of trials investigating the effects of deep neu-
romuscular blockade (NMB) during surgery on surgi-
cal conditions and patient outcomes is steadily growing.1–4
target level of neuromuscular blockade compared to when clinical Nonetheless, consensus on which surgical procedures benefit
judgment alone was used. from deep NMB and especially how to implement it has not

C.K., A.D., and M.C.W. contributed equally to this work and share senior authorship.
Submitted for publication January 13, 2024. Accepted for publication May 2, 2024. Published online first on May 10, 2024.
Kim I. Albers-Warlé, M.D.: Department of Anesthesiology, Radboudumc, Nijmegen, The Netherlands.
Gabby T. J. A. Reijnders-Boerboom, M.D.: Department of Anesthesiology, Radboudumc, Nijmegen, The Netherlands.
Veerle Bijkerk, M.D.: Department of Anesthesiology, Radboudumc, Nijmegen, The Netherlands.
Bart Torensma, Ph.D.: Department of Anesthesiology, Leiden University Medical Centre, Leiden, The Netherlands.
Ivo F. Panhuizen, M.D., Ph.D.: Department of Anesthesiology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Marc M. J. Snoeck, M.D., Ph.D.: Department of Anesthesiology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists. This is an open access article distributed under
the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Anesthesiology 2024; 141:365–74. DOI: 10.1097/ALN.0000000000005050
The article processing charge was funded by the Wolters Kluwer/UKB VSNU Agreement.

A nesthesiology, V 141 • NO 2 August 2024 365

 Perioperative Medicine

been reached. Trials with comparable study protocols reveal For step 1, we pooled neuromuscular monitoring data
conflicting outcomes. More noteworthy and concerning is from the RELAX study (clinicaltrials.gov NCT02838134;
that many trials publish results without neuromuscular mon- n = 96) investigating deep versus moderate NMB in lap-
itoring data, rocuronium dose, or description of how well aroscopic donor nephrectomy14 and the BLISS trial (tri-
they succeeded in reaching the intended level of blockade. alregister.nl NTR5380; n = 150) comparing deep with
Moreover, there is considerable variability in reported doses moderate NMB or a single-shot intubation dose of
between articles aiming for the same level of NMB. The rocuronium during bariatric surgery,15 to determine the
2017 AQUILES consensus study5 assembled a large panel of appropriate induction dose and total dose in mg · kg−1 ·
anesthesiologists and surgeons to establish expert recommen- h−1. In both trials, patients received total intravenous anes-
dations on the use of deep NMB in clinical practice. Expert thesia (TIVA) with propofol and remifentanil, and NMB
opinion was nearly unanimous in the belief that deep NMB was induced and, where applicable, maintained with
is highly suitable in abdominal surgery (94.1%), and more rocuronium. Monitoring was performed with the TOF-

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than 80% of the panelists agreed on the need for consensus watch-SX monitor, with measurements every 5 min for the
protocols applicable to both surgeons and anesthesiologists. RELAX study and every 10 min during the BLISS study.
The European Society of Anaesthesiology and Intensive Care This information was incorporated for the RECOVER
reports insufficient evidence for routine application of deep study (clinicaltrials.gov NCT03608436), comparing deep
NMB but recommends it can be used to improve surgical versus moderate NMB in patients undergoing laparoscopic
conditions when needed.6 Poor surgical conditions are asso- colorectal surgery (n = 178) with TIVA and rocuronium.16
ciated with a higher incidence of surgical complications.7 In NMB measurements were performed every 5 min with
our experience, achieving and maintaining an adequate deep the train-of-four (TOF) scan.17 The automatic TOF–PTC
neuromuscular block (a posttetanic count [PTC] of 1 to 28) (ATP) function was used, which means the TOF scan mea-
throughout surgery can prove challenging even for expe- sures a TOF count, and when the TOF count is 0, a PTC
rienced anesthesiologists. It requires frequent monitoring, is automatically measured. This circle is repeated every
even more so because the potency and pharmacokinetics of 5 min. The induction dose and total dose determined in
neuromuscular blocking agents (NMBAs) like rocuronium step 1 were used in step 2, during which the times to
can be influenced by many factors such as age,9 body mass start continuous infusion and adjustments or additional
index,10 race,11 or the type of anesthetic used,12,13 and no boluses were explored. The resulting concept algorithm
clear-cut dosing guidelines exist.Therefore, a practical dosing was validated in 12 patients in the HIPPO study (clini-
algorithm that can easily be applied when there is an indi- caltrials.gov NCT05562999) in patients undergoing total
cation for deep NMB will likely aid clinicians to reach the hip replacement surgery with TIVA and an additional
desired level of NMB more quickly and accurately. 20 patients undergoing laparoscopic colorectal surgery
To investigate the optimal dosing strategy to reach and during implementation of the algorithm in our hospital.
maintain adequate deep NMB throughout surgery under NMB measurements were also performed every 5 min
total intravenous anesthesia, we have pooled data from our with the TOF Scan. This validation cohort was compared
previous randomized clinical trials investigating deep NMB. to patients from the ongoing EURO-RELAX (clinicaltri-
In this article, we aim to develop a practical clinical dosing als.gov NCT04124757), RECOVER-2 (NCT04250883),
algorithm that can be used to induce and maintain deep and HIPPO18 studies (total n = 180), in which the algo-
NMB throughout surgery. rithm was not used.

Materials and Methods Total Dose and Induction Dose

The algorithm was developed in three steps: (1) determi- In step 1, individual NMB measurements of each patient
nation of the ideal induction dose and total dose in mg · were classified as intense (PTC 0), deep (PTC 1 to 2), deep
kg−1 · h−1 based on actual bodyweight, (2) determination to moderate (PTC 3 to 10), moderate (TOF count of 1 to
of when to start continuous infusion and how to adjust, 2), or shallow (TOF count of 3 to 4; table 1). Patients were
and (3) validation of the resulting algorithm with a com- grouped based on the percentage of NMB measurements in
parison to the success rate without the algorithm (fig. 1). each category throughout the surgery. Patients were assigned
to a group when 75% or more of the measurements were in
Thomas Fuchs-Buder, M.D., Ph.D.: Département d’Anesthésie et de Réanimation,
the same category or to an in-between category (I, II, III or
Centre Hospitalier Universitaire Nancy/Brabois, Nancy, France. IV) when 75% or more of the measurements were divided
Christiaan Keijzer, M.D., Ph.D.: Department of Anesthesiology, Radboudumc, Nijmegen,
over two categories (table 1). Patients that could not clearly
The Netherlands. be categorized due to a large variability in measurements
Albert Dahan, M.D., Ph.D.: Department of Anesthesiology, Leiden University Medical were excluded from analysis. Duration of surgery was
Centre, Leiden, The Netherlands. defined as the time from first incision until closing of the
Michiel C. Warlé, M.D., Ph.D.: Department of Surgery, Radboudumc, Nijmegen, The wound was finished. For patients who received a single shot
Netherlands. of rocuronium (or for cases in which continuous infusion

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Fig. 1. Study design. BLISS study15, HIPPO study18, RECOVER study16, RELAX study14. PTC, posttetanic count.

the algorithm in the same patient category. To investigate

Table 1. NMB Measurements from the RELAX and BLISS whether a learning curve is present in the performance of
Studies the individual residents, the results are split into groups of
20 consecutive patients. The percentage of measurements
Deep to from induction until the end of surgery that are on target
Measurement Intense Deep Moderate Moderate Shallow 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
Category I II III IV V
Count PTC 0 PTC 1–2 PTC 3–10 TOF 1–2 TOF 3–4 is considered statistically significant. Cohen’s d is used to
estimate the effect size.
The individual NMB measurements of patients in the RELAX14 and BLISS15 studies (n
= 246) were each classified into the categories below. Each patient was classified
into one of these categories (when more than 75% of measurements were in the
same category) or to category I, II, III, or IV (when more than 75% of measurements Statistical Analysis and Graphics
were divided over two categories).
NMB, neuromuscular blockade; PTC, posttetanic count; TOF, train of four. The analyses were performed in IBM SPSS Statistics, ver-
sion 27. Images were made with GraphPad PRISM version
919 and Lucidchart.20
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/ Results
kg was compared with an intubation dose of 0.6 (range, The baseline, surgery, and anesthesia characteristics for
0.5 to 0.7) mg/kg. The rocuronium dose was reported as the RELAX, BLISS, and RECOVER study are displayed
mean ± SD. in table 2.

When to Start Continuous Infusion and How to Adjust

Step 1. Rocuronium Dose–Response
The induction dose and total dose found in step 1 were
Neuromuscular monitoring data were available for 239 of
applied in step 2, during which the lowest TOF count or
246 patients. For the RELAX study (patients undergoing
PTC and time to reach this count after the standardized
laparoscopic donor nephrectomy), the mean duration of
induction dose were determined. An explorative analysis of
surgery was 146 ± 38 min; an average of 19 NMB mea-
the effect of additional boluses or adjustment of continuous
surements per patient were used in the analysis. Mean
infusion was performed by identifying the corresponding
duration of surgery in the BLISS study (patients undergo-
increase in NMB depth.
ing bariatric surgery) was 46 ± 15 min, with an average of
6 NMB measurements per patient included in the analy-
Algorithm Validation sis. All patients received total intravenous anesthesia with
To evaluate the accuracy of the algorithm to achieve propofol and remifentanil. Table 3 shows the number of
and maintain deep NMB, we compare the performance patients in each monitoring category: intense (PTC 0),
(defined as the percentage of measurements that are on deep (PTC 1 to 2), deep to moderate (PTC 3 to 10),
target PTC 1 to 2) of four dedicated researchers (anes- moderate (TOF count of 1 to 2), and shallow NMB (TOF
thesiology residents only adjusting the NMB level during count of 3 to 4). More than 75% of measurements were in
the EURO-RELAX, RECOVER-2, and HIPPO study one category for 131 patients, for 92 patients more than
and not otherwise involved in patient care) to the per- 75% of measurements were divided over two categories,
formance when two of these researchers strictly follow they were assigned to in-between categories I, II, III, or

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Table 2. Patient and Surgery Characteristics

Characteristic RELAX14 (n = 96) BLISS15 (n = 150) RECOVER16 (n = 178)

Type of surgery Laparoscopic donor nephrectomy Bariatric surgery Laparoscopic colorectal surgery
Anesthesia TIVA TIVA TIVA
Sex (male/female) 47%/53% 22%/78% 64%/36%
Age, yr 56 ± 10 51 ± 10 69 ± 9
BMI, kg/m2 26.5 ± 3.0 43.1 ± 4.7 26.7 ± 4.5
Duration of surgery, min 146 ± 38 46 ± 15 159 ± 50
NMB (deep/moderate/single shot) 48/48/0 50/50/50 89/89/0
NMB monitoring TOF watch SX TOF watch SX TOF scan

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Note that the HIPPO18 study used for validation is still ongoing but is performed in total hip replacement surgery with TIVA. BLISS study15, RECOVER study16, RELAX study14.
BMI, body mass index; NMB, neuromuscular block; TIVA, total intravenous anesthesia; TOF, train of four.

Table 3. Patient Monitoring Categories

Category A Deep B Moderate C Shallow None Total

Measurement PTC 0 I PTC 1–2 II PTC 3–10 III TOF 1–2 IV TOF 3–4 *
No. of patients 3 8 13 37 26 11 31 36 69 5 239

Patients in each monitoring category were then assigned to A (PTC 0 and category I), deep NMB, B (PTC 3 to 10 and categories II and III), moderate NMB, C (category IV), or shallow
NMB.
*Five patients could not be classified because their measurements were divided across several categories
NMB, neuromuscular block; PTC, post-tetanic count; TOF, train of four.

IV (table 1). Eleven patients for whom measurements of 1 to 2; line B shows that NMB reaches a PTC 1 to 5 and
were divided over three categories were assigned to the that continuous infusion should be started at the right time
best-fitting category; for example, 31% PTC 0, 38% PTC to maintain deep NMB; and line C shows that PTC reaches
1 to 2, and 31% PTC 3 to 10 was assigned to the cate- 0 and that continuous infusion should be delayed until a
gory PTC 1 to 2. Five patients could not be categorized; PTC of 1 is observed. For 68 RECOVER patients receiv-
in four patients the majority of measurements were TOF ing deep NMB, monitoring was sufficiently detailed to
count 0, and no PTC was measured, and for one patient, adequately determine the lowest measurement and time to
the measurements were divided between four catego- reach the lowest measurement. Figure 3 shows that approx-
ries. Figure 2 displays the mean dose of rocuronium in imately a quarter of patients follow curve B and reach a
mg · kg−1 · h−1 for actual bodyweight. For deep NMB, PTC of 1 to 5 after a mean of 11 min after the induc-
the mean required dose was 1.0 ± 0.27 mg · kg−1 · h−1 tion dose of 0.6 mg/kg. The remaining 75% of patients are
(including the induction dose). Comparing spontaneous equally divided over response patterns A and C and need
recovery of neuromuscular function after a single intuba- either an additional bolus and direct start of the continuous
tion dose of 0.3 mg/kg versus 0.6 mg/kg rocuronium in infusion or an approximate 15-min wait after PTC 0 before
BLISS patients revealed that 10 min after administration return of the PTC to at least 1, respectively.
of rocuronium, 75% of patients who received 0.6 mg/kg The effect of a bolus or infusion adjustment was difficult
had a TOF count of 0, compared to 20% of patients who to isolate and compare, because they were often applied
received 0.3 mg/kg. After 20 min, this decreased to 56% simultaneously or one shortly after the other and from a
of patients with a TOF count 0 for 0.6 mg/kg and 5% different NMB starting point. Nonetheless, scoring the
TOF count 0 for 0.3 mg/kg. individual responses generated a fair measure for an algo-
rithm. 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,
Step 2: Continuous Infusion and How to Adjust and a bolus of 15 mg lowers the PTC by 6 to 8 counts.
An intubation dose of 0.6 mg/kg was consistently used in A distinction was made between initial induction toward
the deep NMB arm of the RECOVER trial. This allowed deep versus adjustments and re-evaluation later in the sur-
for identification of three response patterns as shown in fig- gery. Over half of the RECOVER patients reached a sta-
ure 3: line A shows that NMB either remains too shallow ble phase during which no adjustments of the continuous
and that additional intervention is required to reach PTC infusion or additional boluses were needed (mean duration,

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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 cat-
egory 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. 3. Distribution of RELAX14 and BLISS15 patients across the

90 min; range, 30 to 205 min). During longer surgeries, the three possible response patterns for the initial decline of the
PTC tended to drop to 0 after this long stable phase with train-of-four (TOF) count/posttetanic count (PTC) after the intu-
continuous infusion.This drop to PTC 0 occurred on aver- bation dose of 0.6 mg/kg: (A) the level of neuromuscular block-
age after 2.5 h (157 min; range, 92 to 227 min) and often ade 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 contin-
required a strong dose reduction to return to PTC 1 to 2.
uous infusion; or (C) neuromuscular blockade (NMB) becomes
too deep (PTC 0) for X amount of time before returning to PTC
Step 3: Algorithm Validation 1 or 2, and continuous infusion should be delayed until a PTC
of 1 returns. The ranges show the fastest and slowest times to
The concept algorithm was validated by two dedicated reach the lowest NMB measurement; for (A) and (B), continuous
researchers (anesthesiology residents only adjusting the infusion can be started 12 min after the induction dose, whereas
NMB level and not otherwise involved in patient care; in the case of (C), continuous infusion needs to wait up to 25 min.
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% induction dose. Once continuous infusion is started, clini-
of measurements (including the initial decline from TOF cians then reassess and act every one to three measurements
count 4 after induction) were on target PTC 1 to 2. The based on the trend.
algorithm performed significantly better than four dedi-
cated residents (R1, R2, R3, and R4 in fig. 4A) had done Discussion
before without the algorithm (n = 180) after a learning
curve of 0 to 20 patients (a mean 42% PTC 1 to 2, P ≤ In this article, we propose a practical dosing algorithm
0.001, Cohen’s d = 1.4 [95% CI, 0.9 to 1.8]), 21 to 40 to induce and maintain deep NMB with rocuronium in
patients (a mean 37% PTC 1 to 2, P ≤ 0.001, Cohen’s d = patients receiving TIVA. In our validation cohort, 76%
1.6 [95% CI, 1.0 to 2.1]), 41 to 60 patients (a mean 46% of the 5-min measurements were on target PTC 1 to 2.
PTC 1 to 2, P ≤ 0.001, Cohen’s d = 1.5 [95% CI, 0.9 to Although three quarters of measurements on target may not
2.1]), 61 to 80 patients (a mean 43% PTC 1 to 2, P ≤ 0.001, seem like a very high score, this includes the initial decline
Cohen’s d = 1.3 [95% CI, 0.7 to 1.9), and 81 to 100 patients from TOF count 4 after induction. This takes about four
(a mean 61% PTC 1 to 2, P ≤ 0.05, Cohen’s d = 0.7 [95% or five measurements and has to be balanced by 12 (e.g.,
CI, 0.1 to 1.2]; fig. 4). 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 the algorithm. Of course, the question remains whether this
Figure 5 reveals the proposed algorithm for deep NMB small target range is absolutely necessary. Why deep NMB
(PTC 1 to 2) with rocuronium in patients receiving total should be a PTC of 1 to 2 measured at the adductor polli-
intravenous anesthesia. Extrapolating the response patterns cis muscle is outlined in the latest NMB classification arti-
from figure 3 directs that the first assessment of NMB cle8; it is the deepest but still quantifiable NMB that can be
after stabilization 4 is likely approximately 10 min after the achieved. At PTC 0, the exact NMB depth is unknown, and

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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.

we cannot estimate the time to recovery or the required shows the separate scores for each resident, which supports
dose of sugammadex to avoid residual blockade. Recovery that for the first 20 patients there are no major differences
of function at the diaphragm precedes recovery at the m. between residents. Some residents may show a faster learn-
adductor pollicis and at a PTC of 1, diaphragmatic activity ing curve than others, and experienced anesthesiologists
is already at 10% of control. At a PTC of 5 or less, activity is may not need the help, but as long as deep NMB is not
at 21% of control,21 which means that at higher PTC levels, routinely applied in clinical practice, many clinicians will
contraction of the abdominal muscles may impede the sur- remain in the early stages of their learning curve where the
gical field. The algorithm provides a relatively easy way to algorithm could prove helpful.
remain within this range.This is supported by the validation The proposed algorithm and doses are in line with pre-
in which anesthesiology residents who use the algorithm vious pharmacokinetic and pharmacodynamic models and
have more on target measurements than those who do not dose finding studies of rocuronium.22,23 The limitations of
use the algorithm. Especially in the beginning of the learn- this study mainly pertain to generalizability, because it is
ing curve, the effect size of the algorithm is large. Although well known that NMBAs and in particular rocuronium
there can be significant clinical variation in applying deep have a large variability in onset and recovery. Although the
NMB both without the algorithm (e.g., experienced cli- algorithm was developed with different types of surgery, in
nicians who do this often) and with the algorithm (there both sexes, and with a broad range of ages and body mass
is room for interpretation, for example in “reassess and act indexes, it may not be as precise for all patients or types
every one to three measurements”), the aggregated scores of surgery. The algorithm was developed with doses based
of four residents in a total of 180 patients minimize the on actual bodyweight. Particular consideration was given
chances of seeing a resident-specific effect (for example, a to the most appropriate weight metric for dosing in obese
young resident who has little experience in dosing for deep patients. Our algorithm was mainly informed by trials in
NMB but performs well with the algorithm). Figure 4A which actual and ideal body weights were comparable, with

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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 body-
weight. NMB, neuromuscular blockade; TOF, train of four.

an additional trial specifically involving obese bariatric sur- TOF Watch SX measures NMB by acceleromyography,
gery patients. Although Meyhoff et al.24 suggest that dosing and the TOF Scan measures with 3D acceleromyography.
based on ideal or corrected body weight may be preferable These two methods/appliances have a good agreement.26
in such populations to avoid overdosing, our investigations Acceleromyography (AMG) and electromyography are the
into an ideal bodyweight–based strategy did not result in most commonly used quantitative monitoring techniques
a more accurate dose–response relationship. Nonetheless, in clinical practice. Both techniques can “under read,”
dose reductions may be considered when there is a marked where twitches can be seen or palpated that are not regis-
disparity between actual and ideal bodyweight. In addition, tered on the monitor.27,28 Moreover, set-up of each individ-
it is important to keep in mind other influencing factors ual monitor (stabilization, normalization, or use of preload)
like age, renal function, race, and use of anesthetics and can lead to a delay or influence measurements.29 For exam-
adjuncts like magnesium.25 Nevertheless, the algorithm ple, the TOF scan uses a default current of 50 mA, but more
allows for continuous adjustment when the NMB is too may be needed for obese patients, for whom the distance
shallow or too deep. between the electrodes and ulnar nerve is greater, leaving
Finally, the monitoring technique is important to them at risk of not receiving a supramaximal current. The
consider when using the algorithm. The algorithm was STIMPOD NMS 450X has integrated both AMG and
developed with the TOF Watch SX and TOF Scan. the electromyography into one device and allows for choosing

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 Perioperative Medicine

of the most optimal technique based on the clinical setting, Research Support
for example whether the arms of the patient need to be
Supported by Merck Sharp & Dohme (Rahway, New
tucked in during surgery.30 Evidence-based principles for
Jersey; to Dr. Michiel Warlé and Dr. Dahan).
different neuromuscular monitoring techniques in clinical
practice have recently been comprehensively summarized
in BJA Education.31 It is advisable for clinicians to familiarize Competing Interests
themselves with the specifics of their monitoring technique Merck Sharp & Dohme was in no way involved in con-
of choice (and in relation to AMG) for optimal and reliable ceptualization, development of the algorithm, writing, or any
interpretation of measurements. Ideally in the future, the other aspect of this article. The opinions presented here are
algorithm will be programmed into a closed-loop system, those of the authors and do not represent the opinion of
which was already developed for rocuronium with contin- Merck Sharp & Dohme or any of its partners. In addition, Dr.
uous NMB monitoring.32,33 In the meantime, the algorithm

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Dahan reports financial relationships with Enalare (Princeton,
can relatively easily be applied in clinical practice without New Jersey) and Trevena (Chesterbrook, Pennsylvania), and
the need for new devices or software. The algorithm was grants from the Food and Drug Administration (Bethesda,
developed from surgeries with a mean duration of 2 h; it is Maryland) and ZonMw (The Hague,The Netherlands).The
anticipated that surgeries extending well beyond this time other authors declare no competing interests.
frame may necessitate decreased dosages as they progress,
and the final step of the algorithm allows for this reassess-
Correspondence
ment and titration.
The algorithm was developed for use during TIVA Address correspondence to Dr. Albers-Warlé: Geert
as the benefits of deep NMB for surgical conditions Grooteplein zuid 10, 6525 GA Nijmegen,The Netherlands.
during volatile anesthesia seem to be limited, which can [email protected]
be explained by spinal inhibition of motor neuron excit-
ability and peripheral augmentation of NMBA potency References
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374 A nesthesiology 2024; 141:365–74 Albers-Warlé et al.