Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03068260 |
| Other study ID # |
ZUH-TQL-ECS |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
February 14, 2017 |
| Last updated |
March 21, 2018 |
| Start date |
March 15, 2017 |
| Est. completion date |
December 1, 2017 |
Study information
| Verified date |
March 2018 |
| Source |
Zealand University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
ECS is a very common procedure. A 1-year retrospective survey revealed a vast opioid
consumption among the new mothers of approximately (mean±SD) 35±25 mg of oral morphine in the
first 24 postoperative hours despite a multimodal analgesic regimen. The adverse effects of
morphine are well known and include postoperative nausea and vomiting (PONV), itching,
fatigue, constipation, confusion, respiratory depression and delayed mobilization. These
adverse effects are unsound for the new mothers as well as the breast-fed, newborn children.
This study aims to evaluate the efficacy of bilateral Transmuscular Quadratus Lumborum (TQL)
block in reducing postoperative morphine consumption and pain.
Description:
Every year two hundred and twenty patients undergo elective caesarean section (CS) at the
department of obstetric and gynaecologic surgery at Zealand University Hospital. The vast
majority of these patients undergo the surgical procedure under spinal (subarachnoid)
anaesthesia with Bupivacaine with the additive Sufentanil.
There are many ways to perform a caesarean section. The techniques can vary, regarding the
type of skin incision, how the abdominal wall is dissected, how the uterine incision is made,
and finally in which layers are closed after the procedure.
Two common transverse skin incisions are the Pfannenstiels incision and the Joel-Cohen
incision. The Pfannenstiels incision is made 2 to 3 cm cephalad to the pubic bone, slightly
curved so the midportion of the incision is within the shaved area of the pubic hair. The
Joel-Cohen incision is placed 3 cm caudad to the anterior intercristal line; i.e. slightly
more cephalad than the Pfannenstiels incision.
If the Pfannenstiels incision is utilized, the subcutaneous layer, fascia and the parietal
peritoneum are usually dissected sharply, whereas with the Joel-Cohen incision, the
subcutaneous layer is only incised medially, followed by a manual separation of the lateral
tissue. The fascia and peritoneum are dissected bluntly.
At Zealand University Hospital, the skin incision used for elective caesarean sections is the
Joel-Cohen incision. A straight, transverse, 12 cm long incision is made through the
cutaneous layer as described above. The subcutaneous layer is incised only in the most medial
area, through which two small incisions are made on each side of the midline of the fascia.
These incisions in the fascia are then extended laterally with a scissor. The linea alba and
parietal peritoneum are opened bluntly with the fingers. Finally, all the layers of the
abdominal wall are pulled apart at the angles of the incisions, opening the incision
laterally.
The sensory nerve supply to the abdominal wall below the umbilicus consists of the anterior
cutaneous rami of the 11th intercostal nerve, the subcostal nerve (T12), the iliohypogastric
nerve (T12, L1) and the ilioinguinal nerve (L1).
From the intercostal space, the 11th intercostal nerve runs behind the costal cartilage and
enters into the neurovascular plane between the internal oblique- and the transverse
abdominis muscles. Just lateral to the rectus abdominis muscle, the nerve perforates the
dorsal sheath of the rectus muscle and continues through the rectus muscle to end as an
anterior cutaneous branch of the abdominal wall just below the umbilicus. The subcostal nerve
passes under the lateral arcuate ligament, runs in front of the quadratus lumborum muscle and
then perforates the transverse abdominis muscle to enter the neurovascular plane. Here the
subcostal nerve divides into an anterior and a lateral branch, where the anterior branch
innervates the skin in the hypogastrium. The iliohypogastric nerve emerges from the lateral
border of the psoas major muscle and runs in front of the quadratus lumborum muscle behind
the kidney. The nerve perforates the transverse abdominis muscle near the iliac crest and
enters into the neurovascular plane between the transverse abdominis and internal oblique
muscle where it divides into a lateral and an anterior cutaneous branch. The lateral branch
innervates the skin of the gluteal region, whereas the anterior branch perforates the
internal oblique muscle, runs between the internal and external oblique muscle until it
perforates the external oblique muscle 2-3 cm cranial to the subcutaneous inguinal ring and
ends as an anterior cutaneous branch to the skin of the hypogastric region. The ilioinguinal
nerve initially follows the iliohypogastric nerve, just caudad to it, and sometimes
communicating with it in a common nerve. After perforating the internal oblique muscle, it
runs through the superficial inguinal ring and innervates the skin over mons pubis, labia
majora and the upper and medial part of the thigh.
The parietal peritoneum lines the abdominal cavity and is innervated by the same spinal
nerves as its corresponding region of the abdominal wall.
When entry to the abdominal cavity is achieved, an incision in the peritoneum covering the
bladder is made. A superficial, transverse incision is made in the midline of the lower
uterine segment. The rest of the muscular layers are dissected bluntly with a pean until
entering the uterine cavity where after the incision is expanded laterally by pulling in
cephalocaudal direction. The infant is delivered and placenta removed.
The visceral peritoneum covers the uterus anteriorly and posteriorly. Like the parietal
peritoneum, it receives the same afferent nerve innervation as the organ it covers. On each
side of the uterus, the two peritoneal sheets meet and comprise the broad ligament. The
fallopian tubes run between the two sheets in the free edge of this ligament, where the
peritoneum folds. On each side of the fallopian tubes, the round ligament of the uterus and
the ovarian ligament arise anteriorly and posteriorly, respectively. Other ligaments that
support the uterus are the cardinal ligament that attaches the cervix to the lateral pelvic
wall, and the uterosacral ligament that extends backwards from the cervix to the front of the
sacrum. The ovaries are held in place by the ovarian ligament (to the uterus), the suspensory
ligament of the ovary (to the pelvic wall) and the mesovarium (to the broad ligament).
Like most other viscera, the uterus is innervated by sympathetic and parasympathetic fibers,
as well as sensory nerve fibers. It is innervated by the uterovaginal plexus, which fibers
originate from the inferior hypogastric plexus. The inferior hypogastric plexus is paired,
with each half on each side of the rectum, cervix and the bladder and consists of sympathetic
as well as parasympathetic fibers. Pain from the body of the uterus is considered to run with
the sympathetic nerves. Afferent nerves supplying the uterus arise from T10 - T12 and L1.
The fallopian tubes are also innervated by the uterovaginal plexus, as well as the ovarian
plexus. The ovaries have their afferent supply from the 10th intercostal nerve.
After fetal and placental extraction, the uterotomy is closed. Where possible, it is
recommended to close the uterus in-situ. The uterus is closed with a single-layer, continuous
closure. Marcain is sometimes administered subfascially where after the fascia is closed with
a continuous suture. Finally, the skin is closed with an intracutaneous suture.
In the post-anaesthesia care unit (PACU) the patients are administered the multimodal
analgesia regimen currently consisting of oral Acetaminophen 1g, Ibuprofen 400 mg. and
Morphine 10 mg. The addition of oral Morphine 10 mg is not an international standard but has
been so far agreed on locally.
The investigator's research group at Zealand University Hospital has conducted a thorough
retrospective one-year survey for this patient group in order to define the quantity of the
research problem. The electronic anaesthesia files, PACU files and ward files were
meticulously reviewed. The survey revealed accumulated morphine consumptions in the first 24
postoperative hours of 35.7±25.0 mg of oral morphine equivalents in CS patients. This dosage
should be evaluated in relation to the standardised multimodal regimen described above.
Anaesthesiologists have primarily used either epidural catheters or long-lasting opioids as
the basis for the postoperative pain management of expected or manifest moderate to severe
pain. An epidural blockade can be contraindicated for some patients, and might cause bladder
paralysis, lower extremity paralysis, hypotension etc. Also, the epidural technique is
labour-intensive in application as well as in its requirements for monitoring. Thus, the
continuous epidural blockade is not a possibility of interest to the gynecologists and
obstetricians at our hospital. Therefore, until recently opioids have been the sole treatment
of pain, when over-the-counter medicine does not suffice. This presents a problem for the
patients due to the well-known adverse effects of morphine including postoperative nausea and
vomiting (PONV), itching, fatigue, constipation, confusion, respiratory depression and
delayed mobilisation. These adverse effects are bad for the new mothers as well as the
breast-fed, newborn children. All of these adverse effects are well known, and
internationally several anaesthesia associations (ESA, ASA, ESRA, ASRA) are searching for
viable alternatives that can be implemented in the daily clinical practice - alternatives
with the primary focus on the wellbeing of the patient striving to ensure effective pain
relief with minimal adverse effects.
In summary, there could be many potentially positive benefits related to the treatment with
advanced pain-reducing techniques. Postoperative complications to surgery are more frequent
in patients experiencing postoperative pain, and besides reducing the immediate postoperative
pain perception, we consider reduction of the total morphine consumption and the potential of
reducing development of chronic pain through better treatment of the acute pain, as very
interesting and promising for the patients in our study.
To avoid or reduce postoperative pain after CS, numerous regional anaesthetic techniques have
been tried. In the UK, and elsewhere, the combined spinal epidural (CSE) is used, but because
of high demands of time and technical skills, and it's lack of potential to have the epidural
tested with the spinal on top, this technique has never gained ground in Denmark. The
ultrasound-guided (USG) or 'blind' transversus abdominis plane (TAP) block has been
investigated in several studies, but with varying results. Thus, this technique has not been
considered for implementation into the standard anaesthesia regimen for CS at Zealand
University Hospital. In a placebo controlled trial in 2015 with patients undergoing CS,
Blanco et al. found significantly lower postoperative opioid consumption and lower pain
scores in the active group treated with Dr. Blanco's version of an ultrasound-guided (USG)
quadratus lumborum (QL) block - named QLB which much resembles an USG version of the original
blind and landmarked based TAP block. However, the exact mechanism by which Dr. Blanco's QLB
block works is still not clear. The investigators now have the technical capability to
improve perioperative pain management by taking advantage of USG peripheral nerve blocks
(PNBs). At Zealand hospital we have concomminantly with Dr. Blanco described another
so-called QL block technique. We call this technique the transmuscular QL (TQL) block. The
mechanism by which the TQL block works has just been proven in a major cadaveric study.
(submitted for publication Anesth Analg) USG PNBs are applied using a technique based on a
thorough anatomical knowledge and real-time ultrasound images that have evolved rapidly
during the last 10 years. At the Department of Anaesthesiology, Zealand University Hospital,
our research group is among the leaders in Scandinavia within this specific field of
interest. We want to make the use of this pain treatment technique in everyday practice
wherever it is clinically indicated. The research group is headed by associate professor Jens
Børglum, PhD, and he has been deeply involved in this development since 2007.
In relation to abdominal surgery, Jens Børglum and his previous research group have been
involved in research that has described and evaluated the effectiveness of USG bilateral dual
transversus abdominis plane (BD-TAP) blocks, USG ilioinguinal / iliohypogastric nerve blocks
and, more recently, the USG TQL blocks.
Three articles concerning specifically the USG TQL block and its' application has recently
been published from our group alone, showing the increasing interest and focus on the
development of this particular block and the potential abilities with the future knowledge of
the block.
At the Zealand University Hospital several research projects regarding the seemingly very
promising analgesic efficacy of the USG TQL blockade are planned and already in the making.
The Department of Anaesthesiology already conduct a PhD-study in cooperation with the
Department of Urology concerning the TQL block and the management of pain in patients
operated for kidney cancer (nephrectomy) and large pelvis stones (Percutaneous
Nephrolithotomy, PNL). The USG TQL block has shown convincing results in a small pilot-study,
concerning the above-mentioned patients with surgery in the retroperitoneal space, resulting
in very low pain scores and a period without the need for opioids in up to 24 hours
postoperatively.
In our other pilot-studies, the USG TQL block has shown an excellent pain-relieving effect
administered as a bilateral rescue block; i.e. postoperatively after laparoscopic
hysterectomy and other gynaecologic procedures as well as CS.
The TQL block is applied with the patient in the lateral position, with the flank of the side
to be blocked turning upwards. The ultrasound transducer is placed in the transverse position
at the posterior axillary line, just above the iliac crest, and adjusted to visualise the QL
and psoas major (PM) muscles and the transverse process of vertebrae L3 or L4. The needle is
subsequently inserted at the posterolateral end of the transducer and advanced in plane. The
needle is then advanced through the QL muscle until the tip of the needle penetrates the
investing fascia of the QL muscle. The local anaesthetic is then injected in the interfascial
plane, but posterior/superficial to the transversalis fascia (TF) and between the QL and PM
muscles. Confirmation of correct application can subsequently be visualized when the two
muscles are seen to spread apart on the ultrasound image. The TF, which cover the
antero-medial surface of the QL and the antero-lateral surface of the PM, splits in two
layers at the level of the diaphragm. One layer is continuous with the inferior diaphragmatic
fascia and the other continues behind the arcuate ligaments of the diaphragm to be the
endothoracic fascia. This is why the lumbar application of local anaesthetic can facilitate a
block of nerves within the thoracic cage. The injectate will now be in close proximity with
the ventral rami of the segmental nerves in the thoracic paravertebral space and the
sympathetic trunk.
As previously mentioned we have yet unpublished data from a cadaveric study in Innsbruck,
December 2015, conducted by our own group. The results show a very favourable spread of
injectate with the TQL block. Not only does the injected dye in this study spread to colour
the ventral rami of the thoracic spinal nerves up to T9 in the thoracic paravertebral space;
the injectate also spread to colour the thoracic sympathetic trunk. The visceral pain arising
from the intraperitoneal organs travel via different nerves to join exactly in the thoracic
sympathetic trunk before entering the central nervous system. Thus, this seem to indicate
that the TQL block can be used to treat not only the pain from the incisions and tears
superficially to the uterus, but also the pain from the uterus itself, and the adjacent
intraperitoneal organs and structures, which is affected in patients undergoing CS. The
cadaveric study has also shown that the lumbar sympathetic trunk and lumbar plexus were not
affected by the injected dye. These results seem to imply that there would be minimal or no
affection of ambulation or lumbar sympathectomy; i.e. no hypotension or dysfunctional bladder
as can often be observed with the epidural technique. Both findings that coincides with our
clinical experiences from our pilot studies.
The investigators want to perform evidence-based research using the USG TQL for patients
undergoing elective CS. Our hypothesis is that the USG TQL block administered bilaterally and
applied postoperatively in the PACU for the CS patients (with the spinal anaesthesia still
manifest) can reduce the postoperative morphine consumption by 50 % during the first 24
postoperative hours. It is considered a block with very little discomfort for the patient,
when not already anaesthetized, but even more so, when the patient is still anaesthetised in
our area of interest, or at least still somewhat desensitised from the spinal anaesthesia.
All patients scheduled for a CS will be screened according to the inclusion and exclusion
criteria. The suitable candidates will be asked prior to surgery, whether they want to
participate in the trial. If so, following elective CS surgery, the patient will receive the
block, allocated in a randomised fashion to either active LA or placebo. The block will be
performed under standard postoperative monitoring by a trained and skilled physician from the
department of anaesthesia. The active treatment will be a bilateral TQL block with 30 mL
Ropivacaine 0.375% on each side, whereas the placebo group will receive the same volume of
Saline, applied in the exact same way. The patients will all receive the same post-surgical
analgesia regimen, consisting of 1 g Acetaminophen, 400 mg Ibuprofen / 100 mg Celebra, the
latter with larger blood loss evaluated by the anaesthetist and obstetrician, and an IV
Morphine Patient-Controlled Analgesia (PCA) - pump. In order to keep the pooled
administration of local anaesthetic below the accepted maximum recommended dosage, local
anaesthetic infiltration will not be performed by the surgeon. In reference to opioid
consumption, it has been part of a local instruction to receive 10 mg Morphine in the PACU
upon arrival here post-surgically. This is also withdrawn concerning the patients enrolled in
this study, but instead the patient herself will manage the opioid treatment by activation of
the PCA pump.
