This prospective, randomized, double-blinded study was approved by the Biomedical
Research Ethics Committee of Peking University First Hospital (2017-1398). It was
registered at http://www.chictr.org.cn with the identifier number: ChiCTR-INR-17013244. Written informed consent was obtained
from each patient.
Potential participants were screened the day before surgery. Patients aged between
18 and 70 years and scheduled to undergo elective laparoscopic radical or partial
nephrectomy were included. Patients who met any of the following criteria were excluded:
(1) chronic opioid-addiction and/or use of other kinds of analgesic drugs for more
than 3 months; (2) inability to communicate due to severe dementia, language barrier,
or end-stage disease; (3) allergic to local anesthetics; (4) nerve block contraindication
such as an infection in the puncture site or severe coagulation dysfunction; and (5)
refusal to participate in the study. Patients who were eligible for this trial were
taught how to evaluate pain intensity by using the numeric rating scale (NRS, an 11-point scale where 0 indicated no pain and 10 indicated the worst pain) and
how to use a patient-controlled analgesia (PCA) device.
Anesthesia management and surgical technique
All patients were treated per a standardized anesthetic protocol. Besides basic standard
monitoring (electrocardiography, noninvasive arterial blood pressure measurement,
pulse oximetry, bispectral index (BIS), capnography), other interventions, such as
central venous cannulation, invasive arterial cannulation, and/or monitoring using
the Flotrac-Vigileo system were performed according to the patients’ comorbidities.
Anesthesia was induced with 0.15-0.3 µg/kg sufentanil, 1-3 mg/kg propofol, and 0.1-0.2
mg/kg etomidate. Endotracheal intubation was facilitated using 0.15 mg/kg cisatracurium
or 0.6 mg/kg rocuronium bromide. Anesthesia was maintained with propofol infusion,
remifentanil infusion with intermittent sufentanil or sufentanil infusion, with or
without dexmedetomidine infusion, with an aim to maintain BIS values between 40 and
60 and mean arterial pressure and heart rate in a 10-20% interval in relation to the
corresponding preoperative values. Thirty minutes before the end of surgery, intravenous
flurbiprofen axetil 50 mg and tropisetron 5 mg were administered to all patients. On emergence from anesthesia, patients were transferred to the post-anesthesia care
unit (PACU) followed by transferred to the ward 1 h later.
All patients were managed according to a standard postoperative pain management protocol,
i.e., a PCA pump with sufentanil 1.25 µg /ml at a basal rate of 0.5 mL/h and an on-demand
bolus of 4 mL every 10 min with a rigorous rescue analgesia plan. The analgesic aim
was to maintain the NRS pain score below 4. In the PACU, regular pain evaluation was
performed every 30 min. If the NRS score was higher than 7, a first bolus 4 mL from
the pump was administered by medical workers and pain was evaluated 5 min later. If
the score continued to remain higher than 7, sufentanil 3-5 µg was administered according
to the patient’s weight. If however the score decreased to 4 or less, no more rescue
analgesics were administered. In the ward, pain evaluation was performed at 2, 6,
12, and 24 h after the surgery. In addition to these follow-ups, patients were instructed
to request additional medication in case of breakthrough pain. Breakthrough pain control
measures were similar as those in the PACU, except morphine 3-5 mg was administered
instead of sufentanil 3-5 µg. NSAIDS could be used as additional drugs according to
the surgeons’ preference.
The retroperitoneal laparoscopic procedure was usually performed through three ports.
The primary port was invariably placed through the incision made for the creation
of the working space. The location of this incision was just below the tip of the
12th rib on the posterior axillary line. The secondary port was placed 2 cm above the iliac crest on the midaxillary line
while the third port was placed under the costal margin on the anterior axillary line.
In radical nephrectomy, the initial incision was extended ventrally for kidney removal.
Pneumoperitoneum was maintained around 12-14 mmHg throughout the procedure (Fig. 1).
Randomization and intervention
Stratified randomization with a block size of 4 was performed using the SAS statistical
package version 9.3 (SAS Institute, Cary, NC, USA) by an independent biostatistician.
The stratified factor was the type of surgery, i.e., radical or partial nephrectomy.
The randomization results were then sealed in sequentially numbered envelopes and
stored at the site of the investigation until the end of the study. The patients were
randomly assigned to two groups: Group T and Group C. Perioperative management was
identical in both groups except from the drug used in the TAP block. The drug used
in Group T was 0.4% ropivacaine 30 ml while an equivalent amount of normal saline
was used in Group C. Study drugs were provided as clear aqueous solutions in the same
20 ml syringes by an independent pharmacist who did not participate in the rest of
Two anesthetists (Da Huang and Hao Kong) experienced in the technique, under ultrasound
guidance, performed the block. They opened the randomized envelopes and did not participate
in the rest of the study. Ultrasound-guided TAP block was performed immediately after
the induction of anesthesia and about 15 min before skin incision. With the patient
in the supine position, the US probe was placed at the midaxillary line between the
lower costal margin and the iliac crest. At this point, the plane between the internal
oblique and transverse abdominal muscles was identified (Fig. 2A). A special needle
used for nerve block (80 mm or 100 mm, Stimuplex D, Germany) was inserted using an
in-plane technique in the anteroposterior direction. After aspiration, to avoid inadvertent
intravascular injection and abdominal paracentesis, an injection with 2 mL of normal
saline was used to ensure correct positioning of the needle. Then the prepared drug
was injected into this plane. Successful study drug injection was defined as the appearance
of a hypoechoic ellipsoid with well-defined margins on ultrasonic imaging (Fig. 2B).
The anesthesiologist, surgeon, attending staff in charge of the patient, investigators,
and the patients themselves were fully blinded to the group assignment.
Follow-up schedule and outcomes
An investigator (Xue Li) was in charge of the follow-up at several time points in
the first 24 h after surgery. Besides, the electronic medical system was reviewed
to obtain necessary data.
The primary outcomes were opioid consumption during surgery and in the first 24 h
after surgery. The secondary outcomes were as follows: (1) NRS pain scores both at
rest and with coughing at the following time points: immediately awakening from anesthesia,
and 0.5, 1, 2, 6, 12 and 24 h after the operation; (2) time to the first bolus demand
in the PCA system with its required and effective bolus numbers; (3) time to the first
rescue analgesic as well as its frequency and percentage besides the use of the PCA
system; (4) the incidence of postoperative nausea and vomiting (PONV) in 24 h after
surgery and the percentage of antiemetic use; (5) patients’ sleep quality evaluated
by the NRS (an 11-point scale where 0 indicated the best sleep quality and 10 indicated
the worst sleep experience) on the night of surgery day; (6) time to the first ambulation
after surgery; (7) drainage in the first 24 h after surgery; and (8) the length of
hospital stay after surgery.
For assessment of the safety of the technique, complications associated with the TAP
block, anesthesia, and surgery were also recorded. These adverse events included but
were not limited to the following conditions: numbness in the lower extremities, hematoma
and bleeding in the needle trajectory, visceral organ injury, anaphylaxis, local anesthetic
toxicity, airway spasm, hypoxemia, cardiac arrest, new-onset arrhythmia, persistent
hypotension (systolic blood pressure reduction of more than 30% from baseline [average
value in the ward] lasting for at least 15 minutes) and bradycardia (heart rate <
45 beats per minute or a decrease of more than 30% from baseline [average value in
the ward] lasting for at least 5 minutes), major hemorrhage (loss of over one blood
volume [70 mL/kg or >5 L in a 70-kg adult] in 24 h, loss of 50% of total blood volume
in less than 3 h, or bleeding at a rate greater than 150 mL/min), conversion of laparoscopic
surgery to open surgery, and re-operation after leaving the operation room.
Sample size estimation
According to previous studies [7, 8], the TAP block could decrease morphine consumption
by more than 40% in comparison with the placebo within the first 24 h after surgery.
We conservatively assumed that opioid consumption would be reduced by 10% in the TAP
block group. We based our sample size calculation on a previous data analysis from
our clinical follow-up system, which showed that the total dosage of sufentanil in
laparoscopic renal surgery with no TAP block intervention was 36.5 5.4 μg. With the
significance and power set at 0.05 (two-sided) and 90% respectively, the sample size
required to detect differences was 94 patients. Taking into account a drop-out rate
of about 10%, we planned to enrol 104 patients. Sample size calculation was performed
with the PASS 11.0 software (Stata Corp. LP, College Station, TX).
Normally distributed continuous variables were expressed as mean ± SD values and were
compared using a two-tailed Student’s t-test. Non-normally distributed continuous
variables and ordinal data were expressed as median (interquartile range) and were
analyzed using the Mann-Whitney U test. Categorical variables were expressed as number
(percentage) and were compared with Chi-squared analysis or Fischer’s exact test.
Time-event data were analyzed by the Kaplan-Meier estimator, with the difference between
groups compared by the log-rank test. Two-sided P values of less than 0.05 were regarded
as statistically significant. All statistical analyses were performed with the SPSS
statistical package version 22.0 (SPSS Inc, Chicago, IL, USA).