Clinical trial NCT04022733
Conditions: Hernia Abdominal Wall
Sponsor: Ajou University School of Medicine
Start date: 2019-10-30; Completion date: 2021-08-03
Enrollment: 134 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary purpose of this study is to compare the remifentanil requirements in deep versus moderate neuromuscular blocks during the surgical pleth index -guided anesthesia in patients undergoing laparoscopic herniorrhaphy.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Moderate neuromuscular block intervention 2: Deep neuromuscular block
Intervention descriptions: intervention 1: maintaining of moderate neuromuscular block (train-of-four count 1-2) during surgery, reversal using neostigmine 50 ug/kg and glycopyrrolate 10 ug/kg intervention 2: maintaining of deep neuromuscular block (posttetanic count 1-2) during surgery, reversal using sugammadex 4 mg/kg based on actual body weight

Protocol documents:
Prot_000.pdf: 
Study Protocol 
 
 
Official title: Effects of deep neuromuscular block on surgical pleth index-guided remifentanil 
administration in laparoscopic herniorrhaphy: A prospective randomized trial 
 
 
 
NCT number: NCT04022733 
 
Document date: Jan 18, 2022 
 
Institution Name: Ajou University School of Medicine 
 
 
 


1.1 Objectives & Hypotheses  
The purpose of this study is to compare the remifentanil requirements in deep versus moderate 
neuromuscular blocks during the surgical pleth index (SPI)-guided anesthesia in patients undergoing 
laparoscopic herniorrhaphy. 
We hypothesis that deep neuromuscular block using sugammadex will reduce the total remifentanil 
dose during SPI - guided anesthesia for laparoscopic herniorrhaphy, because the deep neuromuscular 
block is associated with less intra-operative nociception. 
 
1.2 Background & Rationale, Significance of Selected Topic & Preliminary Data  
General anesthesia results from a combination of hypnosis, antinociception, and immobility. Referring 
a goal-directed approach to each component, the measurement of neuromuscular paralysis or depth of 
anesthesia has been established as using neuromuscular monitoring or BIS (or PSI). Traditionally, 
clinicians utilize symptoms of the physiological stress response to nociceptive stimuli (i.e. increase of 
heart rate, blood pressure or lacrimation) to guide analgesic administration. However, administration of 
intraoperative analgesics guided by clinical symptoms alone appears to be of very limited value. 
The SPI first introduced in 2007, uses pulse plethysmography and photoplethysmography, both obtained 
from pulse oximetry monitoring, to provide an index of the nociception–anti-nociception balance. It 
correlates with surgical stimuli and dosage of analgesic and predicts the effect of pain stimuli and 
analgesic therapy with greater certainty than common clinical parameters.  
SPI = 100 - (normalised heart beat interval X 0.33 + normalised plethysmographic pulse wave 
amplitude X 0.67) 
SPI had moderate correlation to the stress hormones during general anesthesia. And adjusting the 
remifentanil dosage according to the SPI reduced the consumption of both remifentanil and propofol 
and resulted in faster recovery compared with that according to clinical parameters. During equi-MAC 
anesthesia of 1.0 MAC, sevoflurane and desflurane did not show similar intraoperative remifentanil 
consumption under SPI-guided opioid administration. 
Excessive intraoperative administration of remifentanil leads to opioid induced and acute opioid 
tolerance and opioid-induced hyperalgesia, including non-analgesic side-effects such as 
immunosuppression. 
During laparoscopic surgery, deep neuromuscular block with sugammadex as reversal agent has been 
reported to reduce the postoperative pain than moderate neuromuscular block with neostigmine as 
reversal agent, although being controversial. The cause is postulated that at deep relaxation the tension 


on the abdominal wall exerted by the intra-abdominal pressure is less harmful in comparison to the 
tension created during moderate relaxation.  
 
1.3 Study Design 
- This study is single center, prospective, double blinded, and randomized controlled study. 
- Total 134 patients undergoing laparoscopic herniorrhaphy included in the study.  
- Inclusion criteria: American Society of Anesthesiologists (ASA) class 1, 2, and 3, laparoscopic hernia 
repair needing general anesthesia, and age between 19 and 85 years 
   Exclusion criteria: patients refusal, hyperbilirubinemia, chronic pain, opioid abuse, infection, and 
peripheral disease 
- Using a computer-generated randomization (http://www.random.org), the patients were assigned into 
one of the 2 groups; Moderate neuromuscular block (NMB) group and Deep NMB group. Group 
assignment was concealed with sealed and opaque envelope. Immediately before anesthesia induction, 
the envelope was opened by independent investigator, who performed all interventions (control of NM 
block using rocuronium and reversal of NM block using study drug) but was not involved in outcome 
assessment. The anesthetic provider, patients, and preoperative and postoperative outcome assessors 
were blinded to the type of intervention (group assignment) throughout the study period. 
- Patients monitoring include the noninvasive blood pressure, electrocardiogram, oximetry, and 
bispectral index. Anesthesia is induced with propofol of 2 mg/kg, rocuronium of 0.6 mg/kg and 
remifentanil infusion using TCI (target-controlled infusion). Anesthesia was maintained with 
continuous infusion of remifentanil and sevoflurane 1 MAC. After tracheal intubation, remifentanil 
infusion is stopped. One minute before skin incision, the remifentanil infusion was started in the flash 
mode, the target effect-site concentration of remifentanil was initially set at 3.0 ng/ml. 
Subsequently, remifentanil infusion was continuously adjusted throughout the study period to achieve 
an SPI range between 20 and 50 with maintaining sevoflurane 1 MAC by an independent researcher 
who was blinded to the group allocation. Neuromuscular function is measured at the wrist. The TOF-
SCAN generate the stimulus the ulnar nerve and measure contraction of the adductor pollicis muscle. 
At 15 min intervals, the TOF is measured and in the case of TOF=0, this is followed by the PTC. A 
bolus dose of intravenous rocuronium (5-10 mg) was used to maintain moderate (TOF count of 1-2) or 
deep (posttetanic count [PTC] of 1 or 2) neuromuscular blockade. 
 


- Moderate NMB group: moderate NMB (T1-2), reversal using neostigmine 50 ug/kg + glycopyrrolate 
10 ug/kg  
- Deep NMB group: deep NMB (1-2 PTC), reversal using sugammadex 4 mg/kg based on actual body 
weight  
 
- Primary Outcome  
Remifentanil infusion rate from pneumoperitoneum to removal of laparoscope (primary 
outcome) 
 

SAP_001.pdf: 
Statistical analysis 
 
Official title: Effects of deep neuromuscular block on surgical pleth index-guided remifentanil 
administration in laparoscopic herniorrhaphy: A prospective randomized trial 
 
NCT number: NCT04022733 
 
Document date: Jan 18, 2022 
 
Institution Name: Ajou University School of Medicine 
 
 


 
The primary outcome was the infusion rate of remifentanil during pneumoperitoneum. Based on the 
findings of a previous study, we considered a difference in remifentanil infusion rate >0.032 µg/kg/min 
(16% of mean infusion rate of remifentanil in moderate NMB under SPI-guided anesthesia for 
laparoscopic surgery [mean infusion rate of 0.192 (SD 0.064) µg/kg/min]) as clinically relevant. Based 
on a significance level of 5% and statistical power of 80%, each group required 63 subjects for analysis. 
We enrolled a total of 134 patients to compensate for dropouts and observational variation. 
 Statistical analyses were conducted using SPSS software version 25.0 (IBM, NY, USA). Data are 
presented as mean ± SD, median (interquartile range), and number of patients. The normality of 
distribution was tested using the Kolmogorov–Smirnov/ the Shapiro–Wilk test. Continuous data were 
compared using a two-tailed t test when normally distributed; however, Mann-Whitney U-test was used 
for non-normally distributed data. Categorical data were compared using the Chi-square test or Fisher’s 
exact test, as appropriate. Intergroup comparisons for repetitively measured data were performed by 
unpaired t-test with Bonferroni correction. P-values < 0.05 were considered statistically significant.