Deep Neuromuscular Blockade During Spinal Surgery.5

Eur J Anaesthesiol 2020; 37:187–195
ORIGINAL ARTICLE
Deep neuromuscular blockade during spinal surgery

reduces intra-operative blood loss
A randomised clinical trial
Woon-Seok Kang, Chung-Sik Oh, Ka Y. Rhee, Min H. Kang, Tae-Hoon Kim,
Suk H. Lee and Seong-Hyop Kim
BACKGROUND Spinal surgery is usually performed in the haemodynamic and respiratory status, and postoperative
prone position using a posterior approach. However, the pain scores were evaluated.
prone position may cause venous engorgement in the back
RESULTS The median [IQR] volume of intra-operative sur-
and thus increase surgical bleeding with interruption of
gical bleeding was significantly less in the deep neuromus-
surgery. The prone position also affects cardiac output since
cular blockade group than in the moderate neuromuscular
large vessels are compressed decreasing venous return to
blockade group; 300 ml [200 to 494] vs. 415 ml [240 to
the heart.
601]; difference: 117 ml (95% CI, 9 to 244; P ¼ 0.044). The
OBJECTIVE We hypothesised that deep neuromuscular mean SD surgeon’s satisfaction with the intra-operative
blockade would be associated with less surgical bleeding surgical conditions was greater in the deep neuromuscular
during spinal surgery in the prone position. blockade group than in the moderate neuromuscular block-
ade group; 3.5 1.0 vs. 2.9 0.9 (P ¼ 0.004). In intergroup
DESIGN Randomised, single blinded trial.
comparisons of respiratory variables, peak inspiratory pres-
SETTING University teaching hospital. sure was lower in the deep neuromuscular blockade group
overall (P < 0.001). The median [IQR] postoperative pain
PARTICIPANTS Eighty-eight patients in two groups.
score was lower in the deep neuromuscular blockade group
INTERVENTIONS Patients were randomly assigned to mod- than the moderate neuromuscular blockade group; 50 [36 to
erate neuromuscular blockade or deep neuromuscular block- 60] vs. 60 [50 to 70], (P ¼ 0.023).
ade. In the moderate neuromuscular blockade group,
CONCLUSION Deep neuromuscular blockade reduced
administration of rocuronium was adjusted such that the
intra-operative surgical bleeding in patients undergoing spi-
train-of-four count was one to two. In the deep neuromuscu-
nal surgery. This may be related to greater relaxation in the
lar blockade group, rocuronium administration was adjusted
back muscles and lower intra-operative peak inspiratory
such that the train-of-four count was zero with a posttetanic
pressure when compared with moderate neuromuscular
count 2 or less.
blockade.
MAIN OUTCOME MEASURES The primary outcome
TRIAL REGISTRATION KCT0001264 (http://cris.nih.go.kr).
was the volume of intra-operative surgical bleeding. The
surgeon’s satisfaction with operating conditions, Published online 12 December 2019
Introduction
Spinal surgery is usually performed using a increases bleeding with the risk of interruption of
posterior approach in the prone position, but the surgery. The prone position also produces undesirable
latter causes venous engorgement in the back and haemodynamic changes resulting from compression
From the Department of Anesthesiology and Pain Medicine (WS-K, CS-O, KYR, MHK, SH-K), Department of Orthopedic Surgery, Konkuk University Medical Center (TH-K,
SHL), Department of Medicine, Institute of Biomedical Science and Technology (WS-K, CS-O, KYR, TH-K, SHL, SH-K) and Department of Infection and Immunology,
Konkuk University School of Medicine, Seoul, South Korea (SH-K)
Correspondence to Seong-Hyop Kim, MD, PhD, Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Konkuk University School of
Medicine, 120-1, Neudong-ro (Hwayang-dong), Gwangjin-gu, Seoul 05030, South Korea
Tel: +82 2 2030 5454; fax: +82 2 2030 5449; e-mail: yshkim75@daum.net
0265-0215 Copyright ß 2020 European Society of Anaesthesiology. All rights reserved. DOI:10.1097/EJA.0000000000001135
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.

188 Kang et al.
of large vessels and decreased venous return to out by an institutional statistician using a computer-
the heart.1 – 4 generated list of random numbers and sealed envelopes.
Surgeons and nurses involved in patient care were aware
Deep neuromuscular blockade has been shown to
that the study was being conducted but were blinded to
improve surgical conditions compared with moderate
the details of the study protocols. The surgical procedure
neuromuscular blockade in various surgical proce-
was performed by one surgeon and surgical team using
dures.5–8 In spinal surgery, although many other factors
the same method.
such as the body habitus of the patient and the surgical
equipment are important, an improvement in surgical
Anaesthetic regimen
field conditions can be achieved through reducing muscle
Anaesthesia was induced and maintained by the attend-
tension in the back, and also reducing intra-abdominal
ing anaesthesiologist, who managed anaesthesia using a
and thoracic pressure. This goal may be attainable by
standard regimen but was blinded to the details of the
using deep neuromuscular blockade. Better operating
study protocol. After establishing routine invasive sys-
conditions offer the surgeon easier access to the surgical
temic arterial blood pressure (BP) monitoring by cannu-
field with less damage. However, the effect of deep
lation of the radial artery on the nondominant side and
neuromuscular blockade on surgical bleeding in spinal
noninvasive patient monitoring [pulse oximetry, electro-
surgery in the prone position has not been evaluated.
cardiography and bispectral index (BIS) measurements],
We hypothesised that deep, compared with moderate, electrode strips were placed on the patient’s chest and
neuromuscular blockade would cause less surgical bleed- connected to the noninvasive CO monitoring controller
ing in spinal surgery in the prone position. The study was (NICOM; Cheetah Medical, Vancouver, Washington,
designed to evaluate the effects and superiority of deep USA). After initial calibration of the noninvasive CO
neuromuscular blockade on surgical bleeding in patients monitoring system, the cardiac index (CI) and stroke
undergoing posterior lumbar interbody fusion surgery in volume (SV) variation were monitored continuously.9,10
the prone position. Anaesthesia was induced following administration of
lidocaine 0.5 mg kg1 to reduce the injection pain of
Methods propofol. Propofol 1.5 mg kg1 was administered intrave-
Study population nously to induce anaesthesia, and remifentanil
Approval for this study was granted by the Institutional 0.2 mg kg1 min1 was continuously administered and
Review Board of Konkuk University Medical maintained until the end of surgery. Rocuronium
Center, Seoul, South Korea (KUH 1160070; 29 August 0.6 mg kg1 was administered for muscle relaxation after
2014). The study was registered at http://cris.nih.go.kr loss of consciousness, under the guidance of neuromus-
(KCT0001264, principal investigator: Seong-Hyop Kim, cular blockade monitoring. Tracheal intubation was per-
date of registration: 27 October 2014). After obtaining formed at a train-of-four count of 0. During maintenance
informed consent from patients undergoing posterior of anaesthesia, remifentanil was fixed at a dose of
lumbar interbody fusion (2-level or 3-level) at an anaes- 0.2 mg kg1 min1, and sevoflurane was adjusted to main-
thesia previsit, patients were evaluated prospectively at tain BIS values between 40 and 60. In both groups, the
Konkuk University Hospital from September 2014 to following ventilator (ADU; Datex-Ohmeda, Helsinki,
December 2016. The exclusion criteria were as follows: Finland) settings were used: 4 l min1, consisting of air
an urgent or emergency case; a history of pre-operative at 3 l min1 and oxygen at 1 l min1; tidal volume calcu-
anticoagulant medication or an indication for peri-opera- lated as the ideal body weight [50 (female: 45.5) þ 0.91
tive anticoagulant medication; American Society of (height 152.4)] 8 ml; respiratory rate controlled using
Anesthesiologists physical status classification more than the end-tidal carbon dioxide partial pressure from 35 to
3; age less than 16 years; reduced left and right ventricular 40 mmHg via capnography (S/5 Compact Anaesthesia
function (ejection fraction <40%); previous respiratory Monitor; Datex-Ohmeda); no positive end-expiratory
disease; diagnosed neuromuscular disorder; pre-operative pressure; and inspiratory/expiratory ratio 1 : 2. A central
dysrhythmia; allergy to neuromuscular blocking agents; venous catheter for drug and fluid administration with
family history of malignant hyperthermia; decreased central venous pressure (CVP) monitoring was inserted
renal function (serum creatinine level more than twice into the right internal jugular vein. Pressure transducers
the normal range, urine output <0.5 ml kg1 h1, glomer- (PX600F; Edwards Lifesciences, Irvine, California, USA)
ular filtration ratio <60 ml h1); re-operation and derma- for pressure monitoring were placed in the midaxillary
tological disease that interfered with the attachment of line with guidance from a laser leveler and were fixed to
noninvasive cardiac output (CO) monitoring strips. This the operation table to keep the transducer at the atrial
was a prospective, randomised, single-blinded parallel level during the entire procedure. The patient’s position
(allocation ratio ¼ 1 : 1) study. Patients were randomly was changed from supine to prone using the Wilson frame
assigned to the moderate neuromuscular blockade or before surgery began. Phenylephrine 30 mg [if mean
deep neuromuscular blockade group. For participant arterial BP (MAP) < 60 mmHg and heart rate
allocation, permuted block randomisation was carried (HR) > 40 bpm], ephedrine 4 mg (if MAP < 60 mmHg

Deep neuromuscular blockade for spinal surgery 189
and HR < 40 bpm), or atropine 0.5 to 1.0 mg (if pollicis muscle on the opposite hand and wrist to radial
HR < 40 bpm) was injected to prevent hypotension or artery cannulation. Two surface electrocardiography
bradycardia. Phenylephrine was continuously infused if electrodes were placed on cleaned skin overlying the
MAP less than 60 mmHg did not respond to repetitive ulnar nerve, with one electrode positioned on the ulnar
phenylephrine injections. Nicardipine 0.5 mg was side of the flexor carpi radialis tendon and the other
injected at a SBP more than 180 mmHg or DBP more positioned 3 cm proximal to the first. The transducer
than 110 mmHg, and esmolol 30 mg was injected at a was positioned with the flat side against the thumb.
MAP more than 60 mmHg and HR more than 110 bpm Supramaximal stimuli were applied after autonomic cali-
during anaesthesia. Crystalloid solution (Plasma Solution bration (CAL two modes) of acceleromyography after an
A Inj.; CJ HealthCare, Seoul, South Korea) was adminis- initial tetanic stimulus. If the train-of-four ratio (T4/T1)
tered according to fluid maintenance requirements, redis- was less than 95% or more than 105%, adjustment of the
tribution and evaporative surgical fluid losses based on transducer position and re-CAL were performed. After
body weight (4 ml kg1 h1). The attending anaesthesi- confirming a train-of-four ratio of 95 to 105%, neuromus-
ologist performed additional separate laboratory tests for cular blockade monitoring was started. The train-of-four
cases of acute surgical bleeding. If the haematocrit level mode of supramaximal stimulation (0.2 ms duration, fre-
was more than 30%, then colloid solution (Volulyte, quency 2 Hz, two s duration) was applied at 15 s intervals,
Fresenius Kabi, Bad Homberg, Germany) was adminis- which lasted until the end of anaesthesia.
tered to replace blood loss and maintain haemodynamic
The attending anaesthesiologist opened the sealed enve-
stability until the laboratory values reached the indica-
lope after induction of anaesthesia once the patient had
tions for transfusion. Erythrocytes were transfused when
been positioned prone. In both groups, rocuronium was
the hematocrit level was less than 30%. After surgery, the
continuously infused 15 min after the bolus injection for
patient was changed from the prone to supine position,
tracheal intubation. In the moderate neuromuscular
and all anaesthetic drugs were stopped. A lung recruit-
blockade group, the infusion rate of rocuronium was
ment manoeuvre (holding of one breath at 30 cmH2O for
adjusted to obtain a train-of-four count of one or 2. In
10 s, repeated three to four times) was used to improve
the deep neuromuscular blockade group, the infusion
oxygenation and prevent atelectasis before emergence
rate of rocuronium was adjusted to obtain a train-of-four
from anaesthesia.
count of zero with a posttetanic count 2 or less. The
After the position change and discontinuation of all posttetanic count was measured every 6 min until the end
anaesthetics, an intravenous patient-controlled analgesia of anaesthesia.
(PCA) device (Auto Fuser; Ace Medical, Seoul, South
During the change from supine to prone position or vice
Korea) was connected to the patient, and a continuous
versa, neuromuscular blockade monitoring was on
infusion of analgesics was started. Postoperative pain
standby, and after the position change, monitoring was
control with the PCA device was achieved with fentanyl
resumed. To maintain the correct position of the trans-
1000 mg, ramosetron 0.6 mg and 0.9% saline at a total
ducer and avoid interference, the hand and wrist used for
volume of 100 ml. The amount of fentanyl was adjusted
neuromuscular blockade monitoring were fixed with a
according to the patient’s body weight and age. Before
splint, except for the thumb.
connection of the PCA device to the patient, a fentanyl
50 mg bolus was injected. All neuromuscular blockade monitoring data were saved
in a personal computer using TOF-Watch SX Monitor
Residual neuromuscular paralysis was antagonised by
software. The skin temperature of the hand was mea-
sugammadex 2 mg kg1 in the moderate neuromuscular
sured and kept above 32 8C. The central temperature was
blockade group or 4 mg kg1 in the deep neuromuscular
continuously monitored at the lower oesophagus and
blockade group under the guidance of neuromuscular
kept above 35.5 8C.
blockade monitoring. Tracheal extubation was per-
formed after confirming sufficient recovery (train-of-four
ratio more than 90%; BIS more than 80; ability to open the Measurements
eyes, obey the anaesthesiologist’s verbal commands, and All measurements were performed and recorded by one
maintain a regular breathing pattern). The patient was trained observer who did not participate in patient care
then transferred to the postanaesthesia care unit (PACU) and was blinded to the allocation and details of the study
and, after confirmation of anaesthesia recovery, to the protocol. The primary outcome was the volume of intra-
general ward where postoperative care was managed by operative surgical bleeding and the secondary outcome
the orthopaedic surgeon using the institutional protocol. was postoperative surgical bleeding up to 24 h. The
volume of intra-operative surgical bleeding was recorded
Monitoring of neuromuscular blockade before surgical field lavage, and again at the end of
Neuromuscular blockade monitoring was established and surgery, by measuring the total volume of blood collected
continuously monitored after induction using the TOF- in the suction bottle minus the lavage fluid volume used
watch SX (Organon, Dublin, Ireland) at the adductor for wound irrigation. The difference in weight of the

190 Kang et al.
surgical gauze before and after use was considered to For intergroup comparisons, two-way repeated-measures
correspond to the volume of blood soaked into the gauze. analysis of variance (ANOVA) with the Bonferroni
The volume of postoperative bleeding was recorded for method as a post hoc test was used. For intragroup
24 h by checking the readings of the closed wound comparisons, one-way repeated-measures ANOVA with
drainage system (EZ-VAC; e-G MedISys, Goyang, South the Bonferroni method or Friedman’s test was used.
Korea). Intra-operative transfusion requirement, transfu- Categorical variables were analysed using the x2 test.
sion frequency, operation and anaesthesia times and total Data are expressed as the number, mean SD or median
amount of neuromuscular blocking agent were measured [IQR]. A P value less than 0.05 was considered to indicate
at the end of the surgical procedure. The extubation time statistical significance. For data analysed using the Bon-
was defined as the time from reversal agent administra- ferroni correction, a P value less than 0.008 was consid-
tion to tracheal extubation, and was recorded. Postopera- ered to indicate statistical significance.
tive pain was assessed using a numeric rating scale (0 to
100) at 30 min after transfer to the PACU. The score for
the surgeon’s satisfaction (lowest, 1; highest, 5) with the Results
intra-operative surgical conditions was assessed after Posterior lumbar interbody fusions were performed in
surgery.6 Extremely poor (Score 1) indicated that the 232 patients, of whom 144 were excluded: 50 for refusal to
surgeon was unable to work because of an inability to participate, 43 for previous respiratory disease, 27 for pre-
obtain a visible field due to inadequate muscle relaxation; operative dysrhythmia, 21 for re-operation and three for
poor (Score 2) indicated that there was a visible field, but instrumental error, leaving 88 eligible for the study, with
the surgeon was severely hampered by inadequate mus- 44 in each group (Fig. 1). The study was terminated once
cle relaxation; acceptable (Score 3) indicated that the the planned sample size was attained. No harmful results
there was a wide visible field and acceptable muscle or unintended events due to the investigation occurred.
relaxation; good (Score 4) indicated a wide working field
Personal data and pre-operative coagulation profiles of
with adequate muscle relaxation; excellent (Score 5)
the groups were similar (Table 1). A comparison of peri-
indicated a wide visible working field without any muscle
operative variables between the two groups showed that
rigidity. The following haemodynamic and respiratory
the median [IQR] volume of intra-operative surgical
variables were measured: MAP (mmHg), HR (bpm) and
bleeding was significantly less in the deep neuromuscular
CVP (mmHg) derived from an invasive systemic arterial
blockade group compared with the moderate neuromus-
pressure monitoring device and central venous catheter;
cular blockade group; 300 [200 to 494] ml in the deep
CI (l min1 m2) and SV variation (%) derived from a
neuromuscular blockade group vs. 415 [240 to 601] ml in
noninvasive CO monitoring device and peak inspiratory
the moderate neuromuscular blockade group; difference:
pressure (cmH2O) and mean inspiratory pressure
117 (95% CI, nine to 244 ml, P ¼ 0.044). The volume of
(cmH2O) derived from the monitoring system attached
postoperative bleeding up to 24 h in both groups was not
to the mechanical ventilator. The variables were mea-
significantly different 260 [209 to 390] ml in the deep
sured after induction of anaesthesia in the supine position
neuromuscular blockade group vs. 298 [225 to 395] ml in
(T0), at surgical incision after the patient was changed
the neuromuscular blockade group; difference: 96 (95%
from the supine to prone position (T1), 30 min after
CI, 51 to 243) ml, P ¼ 0.218). Total volume of bleeding
surgical incision (T2), at the first screw insertion using
was not significantly different between groups; 605 [404
posterior lumbar interbody fusion (T3), at skin closure
to 753] ml in the deep neuromuscular blockade group vs.
after the surgical procedure (T4) and 5 min after the
780 [534 to 1050] ml in the moderate neuromuscular
patient was changed from prone to supine (T5). The
blockade group (P ¼ 0.053).
arterial oxygen tension (PaO2, mmHg), arterial carbon
dioxide tension (PaCO2, mmHg) and haematocrit level The mean SD amount of neuromuscular blocking
(%) were measured by arterial blood gas analysis, and the agent was significantly greater in the deep neuromuscular
PaO2/fraction of inspired oxygen (FIO2) ratio was calcu- blockade group than in the moderate neuromuscular
lated and recorded at T0, T2 and T5. blockade group; 127.1 37.2 mg vs. 85.5 30.3 mg
(P < 0.001). The median [IQR] extubation time was
Statistical analysis significantly longer in the deep neuromuscular blockade
The primary outcome was the volume of intra-operative group than in the moderate neuromuscular blockade
surgical bleeding. The mean SD intra-operative surgi- group; 5.0 [4.0 to 6.0] min vs. 3.5 [2.0 to 5.0] min
cal bleeding volume in a pilot study of 10 patients (P < 0.001). The median [IQR] numeric rating scale for
undergoing moderate neuromuscular blockade, and postoperative pain in the PACU was significantly lower in
who were not included in the final analysis, was the deep neuromuscular blockade group than in the
515 192 ml. A minimum detected difference of 25% moderate neuromuscular blockade group; 50 [36 to 60]
between the groups was considered clinically significant. vs. 60 [50 to 70] (P ¼ 0.023). The mean SD score for the
In the pilot study, the haematocrit level at the end of surgeon’s satisfaction with the intra-operative surgical
surgery was 29.5test or the MannWhitney rank-sum test. conditions was significantly higher in the deep

Fig. 1
Enrolement
Assessed for eligibility (n = 232)
Excluded (n = 144)
Not meeting inclusion criteria (n = 91)
Declined to participate (n =50)
Other reasons (n = 3)
Randomised (n = 88)
Allocation
Allocated to moderate neuromuscular Allocated to deep neuromuscular
blockade (n = 44) blockade (n = 44)
Received allocated intervention (n = 44) Received allocated intervention (n =44)
Analysis
Analysed (n = 44) Analysed (n = 44)

Excluded from analysis (n = 0) Excluded from analysis (n = 0)
CONSORT flow diagram.
neuromuscular blockade group than in the neuromuscu- pressure was significantly different overall (P < 0.001),
lar blockade group; 3.5 1.0 vs. 2.9 0.9 (P ¼ 0.004). in that it was lower in the deep neuromuscular blockade
group compared with the moderate neuromuscular block-
The requirement for intra-operative transfusion, transfu- ade group, especially at T2 to 5; 17 [16 to 19] vs. 19 [18
sion frequency, volumes of intra-operative fluid adminis- to 21] cmH2O at T2 (P < 0.001); 18 [17 to 19] vs. 19 [18 to
tration, urine output, and operation and anaesthesia times 20] cmH2O at T3 (P < 0.001); 18 [17 to 20] vs. 19 [18
were not significantly different between the two groups to 20] cmH2O at T4 (P ¼ 0.007); 17 [16 to 18] vs. 19 [17 to
(Table 2). 22] cmH2O at T5 (P ¼ 0.002, Fig. 2 and Table 3).
In intergroup comparisons of intra-operative haemody- None of the variables measured in the intra-operative
namic and respiratory variables, only peak inspiratory arterial blood analysis differed significantly between the
Table 1 Personal data and pre-operative coagulation profiles
Moderate block group, n U 44 Deep block group, n U 44 P value

Age (years) 67 11 67 8 0.906
Sex (male/female) 14/30 13/31 0.817
Height (cm) 153 [149 to 160] 156 [150 to 162] 0.140
Weight (kg) 59.1 [54.6 to 66.9] 58.9 [56.0 to 63.8] 0.809
BMI (kg m-2) 24.9 [23.1 to 27.4] 23.9 [22.3 to 27.1] 0.162
Surgical procedure
2 level/3 level 25/19 26/18 0.829
Coagulation profiles
PT (s) 12.7 [12.2 to 13.1] 12.7 [12.3 to 12.9] 0.534
aPTT (s) 34.2 3.7 34.2 3.9 0.992
PLT (103 ml1) 244 [213 to 294] 255 [221 to 306] 0.846
Data are expressed as mean SD or median [IQR]. aPTT, activated partial thromboplastin time; PLT, platelet count; PT, prothrombin time.

192 Kang et al.
Table 2 Peri-operative variables
Moderate block group, n U 44 Deep block group, n U 44 P value

Blood loss (ml)
Intra-operative 415 [240 to 601] 300 [200 to 494]M 0.044
Postoperative 24 h 298 [225 to 395] 260 [209 to 390] 0.218
Total 780 [534 to 1050] 605 [404 to 753] 0.053
Intra-operative transfusion 0.0 [0.0 to 0.0] 0.0 [0.0 to 0.0] 0.902
Transfusion frequency 10/44 8/44 0.597
Fluid administration (ml)
Crystalloid 800 [700 to 1025] 950 [800 to 1200] 0.125
Colloid 600 [500 to 800] 500 [475 to 725] 0.568
Urine output (ml) 300 [155 to 400] 300 [194 to 450] 0.429
Operation duration (min) 137 [116 to 176] 133 [117 to 180] 0.691
Anaesthesia duration (min) 201 [173 to 238] 195 [177 to 250] 0.531
Amounts of neuromuscular blocking agent (mg) 85.5 30.3 127.1 37.2M <0.001
Extubation time (min) 3.5 [2.0 to 5.0] 5.0 [4.0 to 6.0]M <0.001
Numeric rating scale in PACU for pain 60 [50 to 70] 50 [36 to 60]M 0.023
Surgeons’ satisfaction score 2.9 0.9 3.5 1.0M 0.004
M
Data are expressed as Mean SD or median [IQR]. PACU, postanesthetic care unit. P < 0.05 compared with the moderate block group.
two groups at any time point. The haematocrit level in surgical bleeding was significantly less in the deep neu-
both groups was lower at T2 and T5 than at T0. The romuscular blockade group than the moderate neuromus-
lactate level in both groups was higher at T5 than at T0 cular blockade group, but the volume of blood loss up to
and T2 (Table 4). 24 h after surgery did not differ significantly between the
two groups. In comparisons of haemodynamic and respi-
Discussion ratory variables, only peak inspiratory pressure differed
Our study showed that in patients undergoing posterior significantly, being lower in the deep neuromuscular
lumbar interbody fusion the volume of intra-operative blockade group than the neuromuscular blockade group.
Fig. 2
21
* *
* *
20
Peak inspiratory pressure (cmH2O)
19
18 Moderate block group

Deep block group
17
P < 0.001
16
15
T0 T1 T2 T3 T4 T5
Comparisons of intra-operative peak inspiratory pressure between groups. All data were included in the analysis. Overall difference between the
groups was significant (P < 0.001). In the deep neuromuscular blockade group, the values of peak inspiratory pressure at T2 to 5 were lower than in
the moderate neuromuscular blockade group. T0, after anaesthesia induction in the supine position; T1, at the surgical incision after change from
supine to prone; T2, 30 min after the surgical incision; T3, at the time of first screw insertion; T4, at the time of skin closure after the surgical
procedure; T5, 5 min after change from prone to supine. P < 0.008 compared with deep neuromuscular blockade group.

from supine to prone; T2, 30 min after the surgical incision; T3, at the time of first screw insertion; T4, at the time of skin closure after surgical procedure; T5, 5 min after change from prone to supine. M P < 0.05 compared with T0.
Data are expressed as mean SD or median [IQR]. CVP, central venous pressure; HR, heart rate; MAP, mean arterial blood pressure; T0, after anaesthesia induction in the supine position; T1, at the surgical incision after change
[65.0 to 80.0]MM,MMM,MMMM,MMMMM
The score for surgeon’s satisfaction with the intra-opera-
tive surgical conditions was significantly higher in the
[5 to 9]MM,MMM,MMMM,MMMMM
deep neuromuscular blockade group. In addition, the
deep neuromuscular blockade group had a significantly
T5
[57 to 74]MM,MMM
lower numeric rating scale score for assessment of post-
[16 to 18]M
[1.9 to 3.1]
12.7 4.0
[8 to 10]M
operative pain in the PACU.
73.0
2.5
64
17
8
9
There may a number of reasons for the lower volume of
[65.0 to 75.0]MMM
[58 to 71]MM,MMM
intra-operative bleeding in the deep neuromuscular

11.2 4.6M
[17 to 20]M
[1.8 to 2.8]
blockade group. First, the relaxation of the back muscles

[8 to 13]M
T4
[8 to 9]M
provided by deep neuromuscular blockade might
Deep block group, n U 44
70.0
2.2
64
11
18
improve surgical conditions. Many reports have shown

9
[67.0 to 74.0]MMM
that deep neuromuscular blockade leads to a better

surgical field, compared with moderate neuromuscular
[17 to 19]M
[1.7 to 2.8]
12.1 4.6
[55 to 67]
[8 to 13]M
T3
blockade.5–8,11 Deep neuromuscular blockade may be

[8 to 9]
69.0
2.2
associated with better visualisation through an easier

59
11
18
approach and less traction, and favourable evaluation

[64.0 to 71.0]M
[16 to 19]M
[1.8 to 2.7]
from the surgeon. The higher score of the surgeon’s

12.2 4.1
[55 to 66]
[8 to 13]M
T2
[8 to 9]
satisfaction with the surgical conditions in the deep

67.0
2.2
59
11
17
neuromuscular blockade group suggests that deep neu-

8
[64.0 to 75.0]
romuscular blockade does provide more favourable sur-

[16 to 19]M
[1.7 to 2.5]
12.4 3.9
[53 to 67]
[8 to 12]M
gical conditions compared with moderate neuromuscular

T1
[8 to 9]
71.0
blockade. Several laparoscopic procedures under deep

2.2
58
11
18
neuromuscular blockade have resulted in lower intra-

P < 0.05 compared with T1. MMM P < 0.05 compared with T2. MMMM P < 0.05 compared with T3. MMMMM P < 0.05 compared with T4.
[66.0 to 87.0]
abdominal pressure, compared with moderate neuromus-

[1.9 to 2.9]
13.2 3.2
[54 to 70]
[15 to 18]
T0
cular blockade.6–8 This is associated with profound relax-

[6 to 9]
[7 to 9]
73.5
2.2
60
16
ation of the abdominal and diaphragm muscles. In the

8
8
[62.5 to 83.0]MMM,MMMM,MMMMM
present study, the same reasoning may apply to the back

[6 to 12]MM,MMM,MMMM,MMMMM
[53 to 72]MMM,MMMM,MMMMM
muscles. Moreover, the lower postoperative numeric

rating scale score in the PACU potentially represents
T5
less damage to the back muscles in the deep neuromus-

[17 to 22]M
[1.8 to 2.9]
12.8 4.3
[8 to 10]M
cular blockade group.

72.0
2.3
Second, interestingly, the deep neuromuscular blockade

64
19
8
group had a significantly lower peak inspiratory pressure,

[54 to 67]MMM,MMMM
11.6 4.7M,MM,MMM
but no significant difference in any other haemodynamic

[65.0 to 79.0]
[10 to 15]M
[18 to 20]M
[1.6 to 3.0]
T4
[8 to 10]M
or respiratory variable was apparent between the two

Moderate block group, n U 44
groups. Our previous report revealed that patients with

70.0
2.2
Intra-operative haemodynamic and respiratory variables
60
12
19
a lower peak inspiratory pressure experienced less surgi-

[64.8 to 77.0]
cal bleeding during spinal surgery compared with those

[10 to 15]M
[18 to 20]M
[1.5 to 3.0]
12.4 4.7
[53 to 66]
[8 to 10]M
with a higher peak inspiratory pressure.12 In our previous

T3
71.0
2.2
study, we suggested that a higher peak inspiratory pres-

58
12
19
sure worsens inferior vena cava compression and spinal

[64.0 to 72.0]M,MM
venous engorgement, potentially resulting in greater

[53 to 65]M
[10 to 16]M
[18 to 21]M
[1.6 to 2.7]
13.1 4.8
[8 to 10]M
T2
surgical bleeding. In this study, the deep neuromuscular

blockade of various muscles, such as the diaphragm,
69.0
2.1
59
13
19
abdominal wall and other respiratory muscles, in the

[65.0 to 81.3]
prone position may facilitate expansion of the lung,

[10 to 15]M
[17 to 20]M
[1.8 to 2.6]
13.3 4.5
[53 to 65]
[8 to 10]M
T1
resulting in the lower peak inspiratory pressure in the

73.0
2.2
59
13
19
deep neuromuscular blockade group but with the same

9
[65.8 to 81.5]
tidal volume. This corresponded well with a previous

[1.6 to 2.7]
13.9 3.6
[55 to 69]
[15 to 18]
report, which showed an association between increased

[6 to 11]
T0
[7 to 9]
airway pressure and intra-operative surgical blood loss.13

72.0
2.1
63
16
8
Of note, in our previous study, the difference in CVP

Mean inspiratory
Peak inspiratory
between groups was not significant although the peak

(l min1 m2)
variation (%)
Stroke volume
Cardiac index
MAP (mmHg)
CVP (mmHg)
(cmH2O)
(cmH2O)
pressure
pressure
inspiratory pressure differed by about 4 cmH2O. In this

HR (bpm)
Table 3
study, the difference in peak inspiratory pressure

MM
between groups was about one to 2 cmH2O making it

194 Kang et al.
Table 4 Intra-operative arterial blood gas analysis
Moderate block group, n U 44 Deep block group, n U 44

T0 T2 T5 T0 T2 T5
PaO2/FIO2 ratio (mmHg)a 445.8 473.6 467.0 463.9 459.9 472.2
[416.1 to 490.1] [433.6 to 509.7] [420.4 to 509.7] [429.9 to 512.8] [404.6 to 516.0] [428.4 to 520.5]
PaCO2 (mmHg) 35.8 36.5 37.2 35.4 35.8 36.9
[33.0 to 38.9] [34.1 to 39.0] [35.0 to 40.5] [33.4 to 38.1] [33.9 to 39.2] [34.0 to 39.4]
Hematocrit (%) 35.0 32.0 30.0 35.0 31.0 30.5
[33.0 to 37.0] [30.0 to 34.0]M [28.8 to 32.0]M [33.0 to 37.0] [29.0 to 34.0]M [29.0 to 33.0]M
Lactate 1.1 1.0 1.3 0.8 0.9 1.1
[0.7 to 1.5] [0.8 to 1.4] [0.9 to 1.8]M,MM [0.7 to 1.4] [0.7 to 1.5] [0.8 to 1.6]M,MM
Data are expressed as median [IQR]. FIO2, fraction of inspired oxygen; PaCO2, arterial carbon dioxide tension; PaO2, arterial oxygen tension; T0, after anaesthesia
induction in the supine position; T2, 30 min after the surgical incision; T5, 5 min after changed from prone to supine. a No PEEP and FIO2 0.4. M P < 0.05 compared with T0.
MM
P < 0.05 compared with T2.
improbable that a difference in CVP between groups tension of the back muscles should be measured directly.
would be seen. In addition, CVP is affected by factors This was difficult because of the absence of appropriate
such as cardiac compliance, volume status and others in measurement equipment, the interruption of the surgical
addition to peak inspiratory pressure. field and other factors. Second, a double-blind study
design would have been preferable, but it was difficult
CVP was higher when measured in the prone position
to achieve complete blinding of the attending anaesthe-
(T1, T2, T3 and T4) compared with the supine position
siologist because of differences in the amount of rocur-
(T0 and T5). After changing from the prone to supine
onium administered and the effect on the train-of-four.
position at the end of surgery, the CVP in both groups
Notwithstanding, the study protocol was strictly con-
returned to the baseline value. This may be associated
trolled to rule out bias. Third, this was a single centre
with large vessel compression and decreased venous
study and the difference in blood loss between the two
return to the heart in the prone position.
groups was of borderline significance. Therefore, other
SV variation in both groups was lower at T4 than at the interventions to reduce surgical bleeding, such as the use
other measured time points. Intra-operative fluid admin- of an intra-operative antifibrinolytic agent, would mask
istration including transfusion followed the study proto- the effect of deep neuromuscular blockade. However,
col during surgery, ensuring that fluid balance should deep neuromuscular blockade in conjunction with other
have been adequate at T4. Therefore, the SV variation interventions to reduce surgical bleeding from posterior
values in both groups at T4 were lower. The peak lumbar interbody fusion would probably be more impor-
inspiratory pressure values in both groups were higher tant in patients at high risk for surgical bleeding, such as
at T1 to 5 than at baseline. These higher peak inspiratory those taking anticoagulants, those who are obese, and
pressure values may be related to anaesthesia factors, those needing multilevel spinal surgery and re-operation.
such as atelectasis, increased dead spaces, intrapulmon- Finally, the measured amount of intra-operative surgical
ary shunt and ventilation/perfusion mismatch, in addition bleeding was not completely accurate because of the
to patient position and surgical manipulation.14,15 The impossibility of measuring, for example, blood on the
higher mean inspiratory pressure values at T1 to 5 in the surgical drapes, the surgeon’s gown, or the floor. How-
moderate neuromuscular blockade group and at T4 and ever, since this was the same for both groups, it probably
T5 in the deep neuromuscular blockade group compared did not have a significant effect on the accuracy of the
with baseline were assumed to be due to the same group comparison.
reasons.
In conclusion, deep neuromuscular blockade reduced
The extubation time was longer in the deep neuromus- intra-operative surgical bleeding in patients undergoing
cular blockade group than in the moderate neuromuscu- posterior lumbar interbody fusion. This may be related to
lar blockade group. The dose of sugammadex for reversal deep neuromuscular blockade in the back muscles and
of muscle relaxation was administered according to the the lower intra-operative peak inspiratory pressure com-
degree of muscle relaxation (2 and 4 mg kg1 for moder- pared with moderate neuromuscular blockade.
ate and deep neuromuscular blockade, respectively).
Therefore, the longer extubation time in the deep
Acknowledgements relating to this article
neuromuscular blockade group may be due to deeper
Assistance with the study: none.
muscle relaxation.
Financial support and sponsorship: this research was supported by
Several limitations of the present study should be con- the Basic Science Research Program through the National Research
sidered. First, to compare the effects of moderate and Foundation of Korea (NRF) funded by the Ministry of Education
deep neuromuscular blockade on the back muscles, the (NRF-2018R1D1A1B07047066).

Conflicts of interest: none. 8 Kim MH, Lee KY, Lee KY, et al. Maintaining optimal surgical conditions with
low insufflation pressures is possible with deep neuromuscular blockade
Presentation: none. during laparoscopic colorectal surgery: a prospective, randomized, double-
blind, parallel-group clinical trial. Medicine (Baltimore) 2016; 95:e2920.
9 Keren H, Burkhoff D, Squara P. Evaluation of a noninvasive continuous
cardiac output monitoring system based on thoracic bioreactance. Am J
References Physiol Heart Circ Physiol 2007; 293:H583–H589.
1 Hatada T, Kusunoki M, Sakiyama T, et al. Haemodynamics in the prone
10 Marqu e S, Cariou A, Chiche JD, et al. Comparison between Flotrac-Vigileo
jackknife position during surgery. Am J Surg 1991; 162:55–58.
and Bioreactance, a totally noninvasive method for cardiac output
2 Wadsworth R, Anderton JM, Vohra A. The effect of four different surgical
monitoring. Crit Care 2009; 13:R73.
prone positions on cardiovascular parameters in healthy volunteers.
Anaesthesia 1996; 51:819–822. 11 Madsen MV, Staehr-Rye AK, Gätke MR, et al. Neuromuscular blockade for
3 Yokoyama M, Ueda W, Hirakawa M, et al. Haemodynamic effect of the optimising surgical conditions during abdominal and gynaecological
prone position during anaesthesia. Acta Anaesthesiol Scand 1991; surgery: a systematic review. Acta Anaesthesiol Scand 2015; 59:1–16.
35:741–744. 12 Kang WS, Oh CS, Kwon WK, et al. Effect of mechanical ventilation mode
4 Edgcombe H, Carter K, Yarrow S. Anaesthesia in the prone position. Br J type on intra- and postoperative blood loss in patients undergoing posterior
Anaesth 2008; 100:165–183. lumbar interbody fusion surgery: a randomized controlled trial.
5 Dubois PE, Putz L, Jamart J, et al. Deep neuromuscular block improves Anesthesiology 2016; 125:115–123.
surgical conditions during laparoscopic hysterectomy: a randomised 13 Koh JC, Lee JS, Han DW, et al. Increase in airway pressure resulting from
controlled trial. Eur J Anaesthesiol 2014; 31:430–436. prone position patient placing may predict intraoperative surgical blood
6 Martini CH, Boon M, Bevers RF, et al. Evaluation of surgical conditions loss. Spine 2013; 38:E678–E682.
during laparoscopic surgery in patients with moderate vs deep 14 Hedenstierna G. Respiratory physiology. Miller’s anaesthesia, 7th ed.
neuromuscular block. Br J Anaesth 2014; 112:498–505. Philadelphia: Elsevier Churchill Livingstone; 2010; 361–932.
7 Van Wijk RM, Watts RW, Ledowski T, et al. Deep neuromuscular block 15 Kang WS, Kim SH, Chung JW. Comparison of pulmonary gas exchange
reduces intra-abdominal pressure requirements during laparoscopic according to intraoperative ventilation modes for mitral valve repair surgery
cholecystectomy: a prospective observational study. Acta Anaesthesiol via thoracotomy with one-lung ventilation: a randomized controlled trial. J
Scand 2015; 59:434–440. Cardiothorac Vasc Anesth 2014; 28:908–913.


Deep Neuromuscular Blockade During Spinal Surgery.5

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Eur J Anaesthesiol 2020; 37:187–195