Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04146090 |
| Other study ID # |
CAAE 18245019.6.0000.5373 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 23, 2019 |
| Est. completion date |
February 10, 2021 |
Study information
| Verified date |
October 2019 |
| Source |
Pontificia Universidade Catolica de Sao Paulo |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background. Many studies have demonstrated reduced postoperative pain in patients undergoing
lower pneumoperitoneum pressure level during laparoscopic cholecystectomy. However, most of
them has shown a high risk of bias and low or very low quality of evidence. Considering the
need to evaluate, not only the postoperative pain, but the effect of anesthesia and surgery
on patient recovery and satisfaction, we have designed a prospective, randomised and
double-blinded study to evaluate the quality of recovery, using the Quality of Recovery
Questionnaire (QoR-40), in patients undergoing LC under low-pressure or standard pressure
pneumoperitoneum. Methods. Eighty patients aged 18 to 65 years of age will be randomised into
2 groups: LP (low-pressure - 10mmHg) or S (standard - 14 mmHg) enrolled in the study.
Anesthesia will be induced with remifentanil, propofol and rocuronium and the maintenance
will be achieved with sevoflurane and remifentanil Anesthesiologists and surgeons will not
have access to insufflation pressure display. The primary outcome will be assessed using the
Quality of Recovery Questionnaire (QoR-40) which is a 40-item quality of recovery scoring
system. In addition, the intraoperative rocuronium consumption, time to eye opening (time
from the discontinuation of anesthetics to eye opening), post-operative nausea and vomiting,
pain score, analgesic use, and length of PACU stay (time to Aldrete score ≥ 9) will be
recorded.
Description:
INTRODUCTION
Laparoscopic cholecystectomy (LC) is currently one of the most commonly performed surgical
procedures worldwide. Although it is generally a procedure of short duration and a growing
number of patients are being treated on an outpatient basis, post-operative pain remains a
major reason for prolonged hospital stay, and readmission.1 A number of trials have evaluated
methods to prevent postoperative pain after LC. One of the most tested was low-pressure
pneumoperitoneum (7-10 mmHg) when compared to standard-pressure (12-16 mmHg).2-10 It is well
known that carbon dioxide pneumoperitoneum provides adequate working space and organ
visualization but this may cause several physiologic changes. Many studies have demonstrated
reduced postoperative pain in patients undergoing lower pneumoperitoneum pressure level.
However, a recent Cochrane systematic review have shown a high risk of bias and low or very
low quality of evidence in 20 trials from 21 evaluated. Additionally, the decrease in the
effective working space provided by lower intra-abdominal pressure may increase the technical
difficulty, the incidence the procedure-related injuries and the operative time. 11
Considering the measurements that assess quality of life from the patient's perspective are
increasingly recognized as an important quality metric in perioperative clinical trials, and
the need to evaluate, not only the postoperative pain, but the effect of anesthesia and
surgery on patient recovery and satisfaction, we have designed a prospective, randomised and
double-blinded study to evaluate the quality of recovery, using the Quality of Recovery
Questionnaire (QoR-40) 12, in patients undergoing LC under low-pressure or standard pressure
pneumoperitoneum. Additionally, clinical variables, including time to eye opening, procedural
time, cumulative dose of rocuronium, conversion to open surgery, surgeons' satisfaction, the
occurrence of nausea and vomiting, pain score, use of analgesics, and length of Post
Anesthetic Care Unit (PACU) stay was determined.
METHODS
Study Population This randomised trial was approved by the Research Ethics Committee of the
School of Medical and Health Sciences, Pontifical Catholic University of São Paulo (Sorocaba,
São Paulo - Brazil), on 13 August 2019, 18245019.6.0000.5373 (Chairperson Prof. J.A. Costa).
Written informed consent will be obtained from all participants. Eighty patients aged 18 to
65 years of age, with an AmericanSociety of Anesthesiologists (ASA) physical status I or II,
who will be scheduled to undergo LC at Santa Lucida Hospital, will be enrolled in the study.
Exclusion criteria prior to randomization will include: (i) refusal to participate; (ii)
altered level of consciousness or inability to communicate; (iii) presented with a
contraindication to any of the drugs used in the present study; (iv) history of alcohol or
drug abuse; (v) a body mass index (BMI) ≥ 40; (vi) presence of chronic pain or using opioid;
(vii) history of complicated gallstone diseases like acute cholecystitis, cholangitis or
pancreatitis. Reasons for exclusion following randomization will include; (i) protocol
violations, such as the use of medications not contemplated in the study protocol; (ii)
conversion to an open surgical technique. Subjects will be randomised in a 1:1 ratio
(www.random.org) into 2 groups: LP (low-pressure) or S (standard). Group assignments will be
sealed in sequentially numbered opaque envelopes that will be opened after patient inclusion
into the study. All care providers, researchers, and patients will be blinded to group
assignments.
Anesthetic and Surgical Management Premedication will not be administered. Patients will
arrive at operation room (OR) after an 8-hour fast. Standard ASA monitors will be applied
upon entry into the operating room and anesthesia will be induced with remifentanil 0.5 mcg.
kg-1.min-1 over 3 min followed by propofol 2.0 mg.kg-1 and rocuronium 0.6 mg.kg-1 before
tracheal intubation. Anesthetic maintenance will be achieved with sevoflurane 1% - 3% and
remifentanil 0.3 mcg.kg-1min-1 whenever necessary to keep mean arterial pressure (MAP) and
heart hate (HR) within ± 20% baseline values. Ventilation will be controlled mechanically to
maintain an end-tidal carbon dioxide concentration of 30-40 mmHg. Oxygen and air will be
administered in a ratio of 50%. Insufflation pressure will be maintained in 14 mmHg (group S)
or 10 mmHg (group LP). Anesthesiologists and surgeons will not have access to insufflation
pressure display (it will be covered by an opaque paper and will be set by operating room
personnel). Patients who exhibited reductions in systolic arterial pressure (SAP) greater
than 30% will be given ephedrine (10 mg). Normal saline will be used for fluid replacement
therapy at a rate of 500 mL throughout the first 30 minutes, and, then, 2 mL.kg-1.h-1 until
the end of the surgical procedure. All participants will be given dexamethasone (8 mg) and
ketoprofen (100 mg) at the onset of surgery and ondansetron (4 mg) 15 minutes prior the end
of the procedure. Atropine (0.01 mg. kg-1) and neostigmine (0.015 mg. kg-1) will be used to
achieve T4/T1>0.9 on the Train-of-four (TOF) monitor prior to extubation. At the end of
surgery, intra-abdominal irrigation with normal saline will be performed and the
pneumoperitoneum will be carefully evacuated by manual compression. A total of 20 mL
ropivacaine 0.75% will be injected to the subcutaneous tissue, fascia and parietal peritoneum
through the port sites by the surgeon. The surgical working conditions will be scored
according to an ordinal scale ranging from 1 (extremely poor conditions), 2 (poor
conditions), 3 (acceptable conditions), 4 (good conditions) and 5 (optimal conditions). 13
All surgical procedures will be performed by the same team composed of three experienced
surgeons.
The primary outcome will be assessed using the Quality of Recovery Questionnaire (QoR-40)
which is a 40-item quality of recovery scoring system. In addition, the intraoperative
rocuronium consumption, time to eye opening (time from the discontinuation of anesthetics to
eye opening), post-operative nausea and vomiting, pain score, analgesic use, and length of
PACU stay (time to Aldrete score ≥ 9) will be recorded. Pain will be assessed (at rest and
after asking to cough) using a 0-10 numeric pain rating scale (NRS), where zero means no pain
and 10 the worst imaginable pain. Analgesia will be provided with IV morphine every 5 minutes
to maintain a pain score below 4 (2 mg when the pain score was <7 and 3 mg when it was ≥7).
Following discharge from the PACU (minimum stay 60 minutes and Aldrete score ≥ 9), all of the
participants will be given IV ketoprofen (100 mg) every 12 hours and oral dipyrone every six
hours. Whenever patients judge their analgesia to be insufficient, oral tramadol (100 mg)
will be administered at eight-hour minimum intervals. Postoperative nausea and vomiting
(PONV) will be treated with dimenhydrinate (30 mg) intravenously. An investigator who will be
blinded to group assignment will collect all postoperative outcome data 24 hours following
the surgical procedure. The severity of pain was measured at 15-min intervals during PACU
stay and at 4, 6, and 24 h after surgery. Tramadol consumption and the occurrence of nausea
and vomiting episodes will be also recorded. These findings will be confirmed with the ward
nursing staff. All study patients will be admitted to the hospital for a minimum of 24 hours.
Data Collection The baseline QoR-40 questionnaire will be provided to subjects after informed
consent is obtained in the preoperative holding area, 12 hours after surgery and in the next
day by a blinded investigator. The QoR-40 questionnaire assesses five dimensions of recovery
(physical comfort - 12 items; emotional state - 7 items; physical independence - 5 items;
physiological support - 7 items; and pain - 7 items). Each item was rated on a five-point
Likert scale: none of the time, some of the time, usually, most of the time, and all the
time. The total score on the QoR-40 ranges from 40 (poorest quality of recovery) to 200 (best
quality of recovery).
Statistical Analysis The sample size will be calculated considering 90% power to detect a
10-point difference in QoR-40, which indicates the need to include 31 participants in each
group.
A 10-point difference represents a 15% improvement in the quality of recovery on the basis of
previously reported values of the QoR-40.12,14 Taking possible losses into consideration, the
final sample will include 80 patients.
