Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03441828 |
| Other study ID # |
Registro MISP n.54876 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2020 |
| Est. completion date |
July 31, 2020 |
Study information
| Verified date |
December 2020 |
| Source |
Federico II University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Comparison of the impact of a deep neuromuscular blockade (TOF count = 0 and posttetanic
count [PTC] 1-2) and a moderate neuromuscular blockade (TOF count= 1 - 3) on intraoperative
surgical conditions assessed by the surgeon as a 5 points scale (Optimal= 5 points/ Good= 4
points / Adequate= 3 points / Poor = 2 points / Inadequate = 1 point) in patients undergoing
laparosopy for benign gynecological pathologies.
Description:
Objectives.
The primary outcome of the study is to compare the impact of a deep neuromuscular blockade
(TOF count = 0 and posttetanic count [PTC] 1-2) and a moderate neuromuscular blockade (TOF
count= 1 - 3) on intraoperative surgical conditions assessed by the surgeon as a 5 points
scale (Optimal= 5 points/ Good= 4 points / Adequate= 3 points / Poor = 2 points / Inadequate
= 1 point).
The use of low intraabdominal pressure (IAP) and its impact on the surgical operating
conditions has not yet been adequately defined in the literature, although, it is reasonable
to consider that a deep neuromuscular blockade may be beneficial1, especially in gynecologic
laparoscopic surgery.2, 3
Secondary outcome is to compare the time to discharge from post-anesthesia care unit (PACU)
assessed with the WAKE© score.4 As per protocol adopted in our institution, patients are
evaluated with the Modified Aldrete Score5 before discharging from PACU. However the WAKE©
score , whichis constructed from the basic 10-point Modified Aldrete Score, addsthe "Zero
Tolerance Criteria". In fact, the WAKE© score assigns a score from 0 to 2 to motor function,
blood pressure, level of consciousness, respiratory function and oxygen saturation (with a
maximum score of 10), plus the Zero Tolerance Criteria which address the presence or absence
of pain, postoperative nausea and vomiting (PONV), shivering, pruritus, and orthostatic
symptoms. A patient can be discharged from PACU when the WAKE© score is ≥ 9 and when there
are not present any zero tolerance criteria (no pain, PONV, shivering, pruritus, and
orthostatic symptoms).
The use of low IAP associated with the use of a deep neuromuscular blockade may improve the
respiratory function and reduce the postoperative pain and PONV,1, 6-8 thus reducing the time
spent in PACU.
Clinical hypotheses.
The use of deep neuromuscular blockade may improve the surgical operating conditions and
reduce the time spent in PACU by applying a lower intraabdominal pressure. Sugammadex may be
useful to rapid reverse the neuromuscular block. Therefore, discharge time may be reduced.
Even if all the surgical procedures in this study will be performed as inpatient surgery,
some of this may be possibly performed as outpatient surgery. Evaluating the time to
discharge may be relevant, especially for ambulatory surgery, as the cost may be reduced when
the time spent in PACU is reduced.9
Laparoscopic surgery requires the formation of the surgical field within the peritoneal
cavity by insufflating CO2, and creating a pneumoperitoneum. This type of procedure is not
free of adverse effects10 related to insufflation of CO2 and IAP that can induce changes in
liver function, hemodynamic and respiratory compromise.11, 12 Moreover, the use low
pneumoperitoneum pressure (<12 mmHg) is associated with a significant reduction of
postoperative pain.13 The optimization of the surgical field during laparascopic surgery can
be achieved with a deep neuromuscular block, using low pressure of insufflation.1 The benefit
of using a deep neuromuscular blockade to improve the conditions of laparoscopic surgery is
still controversial.14
This study is a single center, prospective clinical trial. Patients scheduled for gynecologic
laparoscopy surgery with planned duration less than 60 min, will receive a deep (TOF count =
0 and posttetanic count -PTC- 1-2) or a moderate neuromuscular blockade (TOF count= 1 - 3)
according to clinical routine. 50 patients will be studied
Inclusion criteria will be:
- Patients who give written informed consent to the study
- Age: 18-60 years
- ASA risk class: I - II
- Elective gynecologic laparoscopic surgery lasting <60 min (excision of ovarian cyst,
endometriosis)
Exclusion criteria will be:
- Lack of consent
- Body Mass Index (BMI)> 30 Kg/m2
- Patients with renal and hepatic dysfunction
- Neuromuscular disorders
- Known hypersensitivity to study drugs
- Pregnant patients
- Conversion to laparotomy
All patients will be hospitalized (inpatient surgery). One hour before surgery, all the
subjects included in the study will receive 75 mg diclofenac SC, whilst ranitidine 100 mg IV
and ondansetron 4 mg IV will be administered as premedication before entering in the
operating room. Standard monitoring will be applied before induction of anesthesia: ECG,
pulse oximetry, non-invasive blood pressure, BIS, acceleromyography at the adductor pollicis
muscle (TOF-Watch SX ®). A balanced general anesthesia will be adopted. Propofol 2mg/kg and
fentanyl 4mcg/kg IV will be administered during induction.
After calibration and stabilization of the TOF-Watch, tracheal intubation will be facilitated
with rocuronium bromide 1.2 mg/kg in the DNMB, and 0.6 mg/kg in the MNMB. Anesthesia will be
maintained with inhalation of a mixture of air / oxygen 50%/50%, and sevoflurane titrated to
obtain a BIS value between 40 - 60. Neuromuscular block will be maintained intraoperatively
by a) a continuous intravenous infusion of rocuronium at the starting dose of 0.3-0.6 mg / kg
/ h , titrated to maintain a TOF count of 0, and a PTC between 1-2; b) neuromuscular blockade
will be maintained with intravenous bolus of rocuronium (0.15-0.25 mg/kg) titrated to obtain
a TOF count of 1-3. PTC will be evaluated every 5 min, whilst TOF every 15 sec.
After insertion of the Veress needle, pneuomoperitoneum will be accomplished with a set
pressure up to 15 mmHg, but reduced to a value of 9 mmHg after all trocar placements. After
every 15 min from pneumoperitoneum and at the end of the procedure (before desufflation of
pneumoperitoneum), surgeon will be asked to judge the surgical conditions with a five points
scale (Optimal= 5 points/ Good= 4 points / Adequate= 3 points / Poor = 2 points / Inadequate
= 1 point). In case of inadequate or poor surgical field that hampers surgery,
pneumoperitoneum pressure will be increased to 12 mmHg and a bolus of rocuronium will be
given as judged appropriate by the attending anesthesiologist. In this case, the final score
(which is the average of all values) will be automatically 1 (inadequate). At the end of
surgery, after careful desufflation of pneumoperitoneum, sugammadex 4mg/kg in DNMB or 2mg/kg
in MNMB will be administered, and patients will be extubated when TOF-ratio >0.9. In PACU,
the WAKE© score will be evaluated every 5 mins. When the score is ≥ 9 and the zero tolerance
criteria (pain, PONV, shivering, pruritus, and orthostatic symptoms) are not present,
patients will be discharged to ward.
For postoperative pain, diclofenac 50 mg SC will be given after 12 hours from the last
administration with paracetamol 1 gr IV q 6h starting at the end of surgery. Tramadol 1mg/kg
IV will be given as a rescue therapy.
The study will necessitate at least 1 year from IRB approval.
Variables/Time Points of Interest Primary outcome is the evaluation of the intraoperative
surgical conditions assessed by the surgeon as a 5 points scale (Optimal= 5 points/ Good= 4
points / Adequate= 3 points / Poor = 2 points / Inadequate = 1 point).
Every 15 min from pneumoperitoneum and at the end of the procedure, surgeon will be asked to
judge the surgical conditions with this five points scale.
Secondary outcome is to compare the time to discharge from PACU assessed with the WAKE©
score. The WAKE© score will be assessed every 5 minutes from the arrival of the patient in
PACU.
Statistical Methods The data analysis will be based on the intent-to-treat approach. The
primary end-point of the study is the influence of the depth of the NMB on the surgical
conditions assessed by a 5 points scale. For each patient, the final score will be the
average of all values (assessed every 15 min from pneuomoperitonuem and at the end of
surgery). The analysis on the final score will be tested using a t-test or a
Wilcoxon-Mann-Whitney test, using R version 2.15.2 (R: A Language and Environment for
Statistical Computing, Vienna, Austria), with a P-value<0.05 considered significant. Data
will be presented as mean (SD) or median (IQR), as judged appropriate.
The secondary end-point evaluates the difference in time spent in PACU between the two
groups. The analysis will compare the average times to reach a WAKE© score ≥ 9 plus the
absence of the "zero tolerance criteria" (pain, PONV, shivering, pruritus, and orthostatic
symptoms) of the two groups. The WAKE© score will be assessed every 5 minutes from the
arrival of the patient in PACU. The analysis will be tested using a t-test or a
Wilcoxon-Mann-Whitney test, using R version 2.15.2 (R: A Language and Environment for
Statistical Computing, Vienna, Austria), with a P-value<0.05 considered significant. Data
will be presented as mean (SD) or median (IQR), as judged appropriate.
Power/Sample Size:
Based on previous studies,13, 15 a sample size of 50 patients would allow us to detect a
clinically relevant difference in the proportion of optimal surgical space conditions during
the entire procedure with a power of 80% and a type 1 error risk (α) of 5%.
