Journal of

Personalized
Medicine

Article
Effect of Quadratus Lumborum Block on Pain and Stress
Response after Video Laparoscopic Surgeries: A Randomized
Clinical Trial
Virna Guedes Alves Brandão 1, *, Gustavo Nascimento Silva 1 , Marcelo Vaz Perez 2 , Kai-Uwe Lewandrowski 3,4,5
and Rossano Kepler Alvim Fiorelli 6

1 Department of Anesthesiology, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de
Janeiro (UNIRIO), Rio de Janeiro 22290-240, RJ, Brazil
2 Department of Surgery and Anesthesia, Federal University of São Paulo (UNIFESP),
São Paulo 04021-001, SP, Brazil
3 Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA
4 Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá 111321, DC, Colombia
5 Department of Orthopedics at Hospital Universitário Gaffrée e Guinle, Universidade Federal do Estado do
Rio de Janeiro, Rio de Janeiro 20270-004, RJ, Brazil
6 Department of General and Specialized Surgery, Gaffrée e Guinle University Hospital, Federal University of
the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 22290-240, RJ, Brazil
* Correspondence: virnabrandao@yahoo.com.br

Abstract: Background: There are many surgical and anesthetic factors that affect pain and the
endocrine–metabolic response to trauma. The ability of anesthetic agents and neuronal blockade to
modify the response to surgical trauma has been widely studied in the last few years. Objective: To
evaluate if the anterior quadratus lumborum block contributes to improved surgical recovery, using
as parameters analgesia, pulmonary function and neuroendocrine response to trauma. Methods: We
carried out a prospective, randomized, controlled, and blinded study, in which 51 patients scheduled
for laparoscopic cholecystectomy. Patients were randomly selected and assigned to 2 groups. The
Citation: Brandão, V.G.A.; Silva, control group received balanced general anesthesia and venous analgesia, and the intervention
G.N.; Perez, M.V.; Levandrowski, group was treated under general, venous analgesia and anterior quadratus lumborum block. The
K.-U.; Fiorelli, R.K.A. Effect of parameters evaluated were: demographic data, postoperative pain, respiratory muscle pressure
Quadratus Lumborum Block on Pain and inflammatory response to surgical stress with the plasma dosage of IL-6 (Interleukin 6), CRP
and Stress Response after Video
(C-Reactive protein) and cortisol. Results: Anterior quadratus lumborum block induced the slowing
Laparoscopic Surgeries: A
of IL-6 cytokine production and a decrease in cortisol release. This effect was accompanied by
Randomized Clinical Trial. J. Pers.
the significant reduction of postoperative pain scores. Conclusion: Anterior quadratus lumborum
Med. 2023, 13, 586. https://doi.org/
block is an important strategy for analgesia in abdominal laparoscopic surgery and contributes to
10.3390/jpm13040586
reducing the inflammatory response to surgical trauma with an early return of preoperative baseline
Academic Editors: Changsheng physiological functions.
Huang and Kenneth P.H. Pritzker

Received: 12 January 2023 Keywords: quadratus lumborum block; laparoscopic surgeries; physiological stress response; postoperative
Revised: 1 March 2023 pain; postoperative period
Accepted: 22 March 2023
Published: 27 March 2023

1. Introduction

Copyright: © 2023 by the authors.

The introduction of laparoscopic surgery was an important milestone in the evolution
Licensee MDPI, Basel, Switzerland.
of the surgical treatment of gallbladder pathologies. This technique is now known to shorten
This article is an open access article
recovery and attenuate the inflammatory response resulting from surgical procedures [1]. It
distributed under the terms and is associated with decreased pain scores, wound infection rates, shorter hospital stays, and
conditions of the Creative Commons an earlier return to work [2]. Most cholecystectomies are performed by laparoscopy, this
Attribution (CC BY) license (https:// procedure being the most common elective gastrointestinal surgery, with approximately
creativecommons.org/licenses/by/ 700,000 procedures performed annually in the United States.
4.0/).

J. Pers. Med. 2023, 13, 586. https://doi.org/10.3390/jpm13040586 https://www.mdpi.com/journal/jpm

J. Pers. Med. 2023, 13, 586 2 of 14

Video laparoscopy promotes hemodynamic changes by the combination of factors such

as pneumoperitoneum, hypercapnia, positioning and anesthetic technique administered to
the patient [3]. The use of ideal pneumoperitoneum is vital in safe laparoscopic surgery
to ensure visualization of the surgical field and the lower cardiovascular and respiratory
repercussions for the patient. However, the increase in intraperitoneal pressure is caused
by regional blood flow, generating ischemia and reperfusion after its deflation [4].
Although postoperative pain (POP) is less frequent and more easily controlled after
minimally invasive procedures than after procedures performed via laparotomy, there is
still no consensus on the effectiveness of control measures. With the video laparoscopic
technique, the most frequent complaint is related to visceral pain and shoulder pain,
resulting from diaphragmatic irritation in pneumoperitoneum caused by CO2 , which affect
35 to 60% of patients [5]. Pain at the surgical site is one of the factors that also influences
the appearance of hypoventilation in the immediate postoperative period. In addition,
thoracic and/or abdominal surgeries involve the respiratory muscles, leading to a decrease
in strength [6], and are related to hypoxemia and/or acute respiratory failure, with a high
prevalence of postoperative complications [7].
Three types of pain occur after laparoscopy [8]: visceral pain, abdominal wall pain,
and shoulder tip pain. Visceral pain most often occurs as a result of surgical manipulation
and irritation of the parietal peritoneum and diaphragm by carbon dioxide gas trapped
and dissolved in the abdomen. Placing the patient in the Fowler position during the
procedure also contributes to this. A somatic type of pain occurs due to the trocars (surgical
instrument) entering the abdominal wall. Pain can also result from electrocautery and
irritation caused by peritoneal bile contamination. Previous studies have shown that the
inflammation that occurs after cholecystectomy in the gallbladder bed, liver, diaphragm
and parietal peritoneum causes pain and nausea [9].
Incisional pain produces a shallow breathing pattern and restrictive dysfunction,
which lead to hypoxemia and pulmonary complications. The degree of pain like has an
important role in the generation of this cascade. The incisions, the damage to visceras and
traction by the pneumoperitoneum lead to inflammatory responses that may affect patients’
postoperative rehabilitation [10].
Trauma triggers an organized tissue response involving the central nervous system,
the hypothalamic–pituitary–adrenal axis, and the immune system. Tissue damage is identi-
fied by peripheral and central nociceptors that elicit an axonal membrane depolarization
response. The electrical impulse generated by the activation of these nociceptors is trans-
mitted by nerve fibers to the dorsal horn of the spinal cord, initiating the activation of
the central nervous system and an immediate sympathetic neurological response. Af-
ter the immediate adrenergic response, different times of systemic endocrine, tissue and
hemodynamic response follow [11].
The immune response to trauma is mediated by the perioperative expression of cy-
tokines. Cytokines indicate the activation pathway of the immune response and cell type
involved. They are soluble proteins and polypeptides that act as messengers of the immune
system. Produced by a variety of cell types, including monocytes, macrophages, lym-
phocytes, and endothelial cells, they may exert a pro-inflammatory or anti-inflammatory
function depending on the effector site. Cytokines are essential for physiological and
immunological homeostasis. They are produced in response to a variety of physiological
and pathological stimuli. The increase in Interleukin-6 (IL-6) has been associated with
an exacerbated response to trauma, being used as a global inflammatory marker. It is be-
lieved that IL-6 is the main inducer of acute-phase proteins, such as hepatocyte C-reactive
protein (CRP), in addition to causing the differentiation, proliferation and maturation of
hematopoietic progenitors [12,13].
IL-6 is a pro-inflammatory cytokine that exerts local and systemic effects, promoting
the activation of the immune system, fighting its infection and initiating biochemical
mechanisms of healing and tissue repair. It is the main cytokine to be released after
J. Pers. Med. 2023, 13, 586 3 of 14

surgery and can be considered a reliable marker of the inflammatory response to surgical
trauma [13].
It is produced by macrophages and T helper type 2 (Th2) lymphocytes. It activates
the inflammatory cascade, acts on the activation of lymphocytes and the differentiation of
antibody-producing B cells, promotes the production of acute-phase proteins and has an
endogenous pyrogenic effect. In a clinical study carried out to evaluate the relationship
between the magnitude of the trauma and the increase in serum IL-6 in an emergency
setting, a direct relationship was found between the increase in IL-6, and the degree of
trauma, morbidity and mortality. Therefore, dampening the release of IL-6 may mean
control the response to trauma [14].
CRP is considered an opsonin and an activator of innate immune cells, particularly
neutrophils, in addition to having anti-inflammatory and pro-inflammatory properties.
Elevations in CRP levels begin approximately 4–6 h after operative injury and usually
peak within 48 h. After uncomplicated operations, its levels begin to decline and usually
normalize within 72–168 h. Therefore, it is perhaps not surprising that, given their relation-
ship and plasma kinetics, both IL-6 and CRP seem to similarly reflect the magnitude of
surgical trauma.
The response to surgical stress is characterized by the secretion of pituitary hormones
and the activation of the central nervous system [11]. Controlling the endocrine response is
an important strategy for controlling postoperative outcomes after trauma. Metabolic and
hydroelectrolytic changes, resulting from the adrenergic response to the effector endocrine
tissue, can precipitate deleterious events in a susceptible organism. Therefore, the use of
a multimodal anesthesia, with strategic drugs with different mechanisms of action and
regional blocks, is crucial when this objective is being pursued [15–17].
There are many surgical and anesthetic factors that affect the response to trauma, and
the control of the inflammatory factor is considered of great importance [18]. It has also been
postulated that decreasing or abolishing the endocrine metabolic response to the operation
may reduce morbidity [10]. The ability of anesthetic agents and neuronal blockade to
modify the endocrine and metabolic response to surgical trauma has been widely studied
in the last few years [11]. Anesthetic management can affect the immunostimulatory and
immunosuppressive mechanisms indirectly by modulating the function of immune cells
or directly by the attenuation of the stress response, either by the use of venous agents or
regional blocks. Therefore, the type of anesthetic technique may alter the balance between
pro- and anti-inflammatory responses, affecting clinical outcomes [19]. The anesthetic
blocks allow the blockade of the afferent and efferent sympathetic pathways at relatively
low doses, resulting in the profound suppression of hemodynamic and stress responses to
surgery. The development of improved recovery protocols in surgery with strategic drugs
and regional blockades, aiming to accelerate the return to habitual activities and to decrease
the statistics of adverse events in the perioperative and hospital costs, is increasingly
necessary [20].
Truncal blocks, as part of perioperative pain management, were introduced into
clinical practice over 40 years ago. Initially used with the ilioinguinal–iliohypogastric block
and the rectus sheath block, they are more commonly used in the pediatric anesthesia
population. Initially, these blocks were performed without ultrasound guidance, using
reference techniques. However, the clinical use of truncal block techniques has developed
over time and its expansion has been driven by the introduction of ultrasound in the practice
of anesthesiology. Although anatomical markers are reliably detected by ultrasound,
anterior abdominal wall blocks vary in both the distribution of local anesthetics and the
field of coverage. In the search for greater analgesia coverage and a longer duration of
postoperative analgesia, fascia transverse plane block and quadratus lumborum block
(QLB) were developed [21].
The successful use of QLB with all approaches has been reported in case reports for the
following surgical procedures: proctosigmoidectomy, hip surgery, above-knee amputation,
abdominal hernia repair, breast reconstruction, colostomy, closure, radical nephrectomy,
J. Pers. Med. 2023, 13, 586 4 of 14

lower extremity vascular surgery, total hip arthroplasty, laparotomy, and colectomy. Several
other cases report a variety of indications for QLB, documenting that sensory blockades
include the T7–L2 dermatomes [22].
The objective of this study is to evaluate if blocking in the form of anterior QLB, also
known as type 3, contributes in a way which attenuates surgical repercussions, having as
its primary parameter analgesia and as its secondary parameters the pulmonary function
and neuroendocrine response to trauma.

2. Subjects and Methods

The patients were treated in the Deparment of Surgery of the Gaffrée e Guinle Univer-
sity Hospital, Federal University of the State of Rio de Janeiro (UNIRIO). The surgical clinic
and anesthesiology departments are accredited by the Federal Ministry of Education and
the Brazilian Society of Anesthesiology (SBA). Standard anesthetic techniques and protocols
were used. The study was conducted after receiving approval by the Ethics and Research
Committee of the mentioned hospital in June 2020 with CAAE nº 26859319.90000.5258 and
was registered on the Brazilian clinical trial registration platform (RBR-96xv826).

2.1. Sample Selection and Anesthetic Technique Standardization

After applying and signing the informed consent form (ICF), 51 of 56 patients with
American Society of Anesthesiology (ASA) I and II were treated by laparoscopic chole-
cystectomy from October 2020 to June 2021 at the Gaffrée e Guinle University Hospital
(Figure 1). Patients were randomized to two groups in a double-blinded manner. Anesthetic
blocks were performed by the same researcher (VGAB) who knew the patient’s group at the
time of surgery (control or intervention). Randomization was performed using computer-
generated numbers. These codes were placed in sealed and numbered envelopes, which
were chosen by the surgeon on the day of surgery. The patient was unaware of whether
they belonged to the control or intervention group and the participants’ registration data
were replaced by codes for the concealment of personal information. The evaluations were
performed by another anesthesiologist (GNS) who did not know which technique had been
performed. Postoperatively, patients’ pain was assessed with the visual analogue pain scale
(VAS). Laboratory and respiratory tests were also performed.
Considering the eligibility criteria of the study, the patients were excluded from the
study for: refusal to participate in the study; body mass index (BMI) greater than or equal to
40; smoking history or obstructive pulmonary disease, presence of peripheral neuropathies;
coagulopathies or hypersensitivity to drugs used for analgesia; infection at the puncture
site; cholecystitis, deformities or previous spinal operations; dementia or other states that
would prevent the adequate understanding of the use of the numeric VAS pain scale;
immunological diseases, malignant neoplasia, use of opioids or anti-inflammatory drugs in
the preoperative period; use of antidepressants and anticonvulsants; and requirement of
conversion of surgery to conventional technique (open surgery).
All patients upon admission to the operating room were monitored according to
the recommendations of the ASA and received peripheral venous access with an 18 or
16 intravenous catheter. All surgeries were performed under balanced general anesthe-
sia; both groups received routine venous analgesia. The intervention group additionally
received ultrasound-guided anterior QLB, which was performed with the patient anes-
thetized soon after the induction of general anesthesia. The anesthetic drugs and their
dosages were standardized so that there were no differences between the groups. The
induction of general anesthesia involved the following: propofol 2.5 mg/kg, rocuronium
0.5 mg/kg and fentanyl 5 mcg/kg. Intraoperative maintenance involved the following:
sevoflurane 1–2 CAM with oxygen 50% and air 50%. All patients received dipyrone at
a dose of 30 mg.kg−1 intravenously and ketoprofen 100 mg EV at the end of surgery, in
addition to infiltration of the surgical portals with ropivacaine 0.3% volume of 10 mL. In
the immediate postoperative period, all patients received intravenous ketoprofen 100 mg
in regular doses of 12/12 h, and only received common analgesics (intravenous dipyrone,
 J. Pers. Med. 2023, 13, 586 5 of 14

, x FOR PEER REVIEW 30 mg/kg/dose 6/6 h) or opioids (50 mg tramadol, intravenous, 6/6 h) if pain 5was
of greater
15
than 5. Ondansetron 4 mg was administered intravenously in the intraoperative period for
the prophylaxis of nausea and vomiting. Surgical time was similar between the groups,
lasting less than 3 h.

Figure 1. CONSORT study flow diagram.

Figure 1. CONSORT study flow diagram.
2.2. Anterior Quadratus Lumborum: Considerations and Block Description
Ultrasound-guided quadratus lumborum block (QLB) is a recently described fascial
Considering the eligibility criteria of the study, the patients were excluded from the
plane block in which the anesthetic is injected adjacently to the quadratus lumborum (QL)
study for: refusal to
muscle with theingoal
participate theofstudy; body mass
anesthetizing indexin(BMI)
the nerves greater than
the thoracolumbar or equal
region [16]. It is
to 40; smoking history or that
believed obstructive pulmonary
the anesthetic, disease,into
injected anteriorly presence of peripheral
the QL muscle neurop-
and posteriorly into the
athies; coagulopathies or hypersensitivity to drugs used for analgesia; infection at the and
transversalis fascia, will disperse into the paravertebral space, travelling posteriorly
laterally to the arcuate ligaments of the diaphragm along the endothoracic fascia in order
puncture site; cholecystitis, deformities or previous spinal operations; dementia or other
to block the somatic nerves and the sympathetic trunk according to the level of dispersion
states that would prevent the adequate
of the anesthetic. Anteriorunderstanding
QLB can generate ofanalgesia
the use from
of the
T10numeric
to L4. ForVAS painQLB
subcostal
scale; immunological diseases,
(Anterior malignant
QLB subtype), localneoplasia,
anesthetic, use of opioids
injected anteriorlyorintoanti-inflammatory
the QL between the QL
muscle and
drugs in the preoperative into theuse
period; anterior layer of the thoracolumbar
of antidepressants fascia, caused cephalad
and anticonvulsants; dispersion
and require-
near the T12 rib with the displacement of the
ment of conversion of surgery to conventional technique (open surgery). anterior lamina of the thoracolumbar fascia.
This produces reliable dermatomal coverage from T6–T7 to L1–2 [23].
All patients uponAs admission to the operating room were monitored according to the
QLB is a classic method of injecting intramuscular (interfascial) medication, the
recommendations possibility
of the ASA and received
of infection is much peripheral venous
lower than when accessneuraxial
performing with anblocks.
18 or To
16 date,
in- no
travenous catheter. All surgeries were performed under balanced general anesthesia; both
groups received routine venous analgesia. The intervention group additionally received
ultrasound-guided anterior QLB, which was performed with the patient anesthetized
soon after the induction of general anesthesia. The anesthetic drugs and their dosages
J. Pers. Med. 2023, 13, 586 6 of 14

infections have been described as a result of QLB. The advantage of the QLB over other
abdominal wall blocks is the fact that the passage of the needle and the site of application of
the local anesthetic are far from the peritoneal cavity, the visceral abdominal organs and the
large blood vessels. Therefore, needle trauma is minimized here in terms of unintentional
puncture of the peritoneum, intestine, liver, kidney, and large blood vessels associated with
blind (non-ultrasound) methods of TAP and II-IH block performance. Performing QLB
under ultrasound control, with mandatory monitoring of the needle tip carried out before
drug injection, significantly increases the level of safety and efficiency of the technique.
There are no data on neurological damage, as the local anesthetic is not injected in the
immediate proximity of the large nerve but is injected into the space which is rich in small
nerve endings. Therefore, it is generally accepted that QLB can be performed under general
and regional anesthesia [24]. The current literature on QLB reports the use of 4 different
approaches, with authors using varying nomenclatures to describe each block. It has
been classified based on the anatomical location of the needle tip in relation to the muscle.
Thus, the following terminology is adopted: posterior, lateral, anterior, and intramuscular
approaches [22].
In this study, the anterior or type 3 QLB was performed right after anesthetic induction.
A low-frequency curvilinear transducer was used to facilitate tissue penetration of the
ultrasound and the establishment of a wide field of view. With the patient in lateral
decubitus, the transducer is placed in transverse orientation on the posterior or midaxillary
line at the L2–L4 level in order to visualize the QL and psoas muscle. To identify the QL
muscle, it is important to observe some structures as reference, such as the aponeuroses of
the abdominal wall muscles (external oblique, internal oblique and transverse abdominal)
which are located posterolaterally to the muscle. The QL muscle is often hypoechoic in
relation to the psoas major muscle, which is located anteromedially. Additionally, the
lumbar transverse processes are apparent due to their curved hyperechoic appearance.
The recommended dose of local anesthesia varies from 0.2–0.4 mL/kg of 0.2–0.5%
Ropivacaine or of 0.1–0.25% Bupivacaine. The dose was adjusted respecting the toxic dose
of the local anesthetic and the anterior QLB performed bilaterally. In this study, 20 mL
of 0.3% Ropivacaine was administered bilaterally (total of 120 mg) using a Stimuplex
A100 needle.

2.3. Pain Evaluation

The efficacy of analgesia produced by the two techniques studied was evaluated at
regular intervals by the numeric verbal rating scale (NVRS). Patients were asked to answer
the question, “Are you feeling pain? How severe is the pain on a scale of 0–10 (0—no
pain; 10—the most severe pain)?”. The intensity of pain was measured 1 h, 4 h and 24 h
postoperatively by this scale, and the consumption of pain killers (tramadol) was also
recorded. Categories were constructed based on the intensity of pain reported by the
patients, with the value 0 being considered Painless; 1–3 being considered “Light”; 4–6
“Moderate”; and 7–10 “Severe” pain.

2.4. Laboratory Assays

For the determination of the markers of inflammatory response measuring IL-6, CRP
and cortisol, samples were collected at anesthetic induction (preoperative) and at 4 h and
24 h after the surgical procedure had been performed. The blood samples of the research
participants were collected in a tube without additives and the serum was preserved at
−112 ◦ F until the moment of analysis without freezing and thawing cycles. The trials were
conducted in the laboratory of the National Program for Quality Control (NPQC), in the
state of Rio de Janeiro. The research participant did not know the analgesia technique
performed in each procedure. IL-6 serum concentration was determined by the electro-
chemiluminescence immunoassay (ECLIA) using the Roche Cobas e411 immunoassay
analyzer. CRP serum concentration was determined with the immunoturbidimetric assay
using the Bioclin 3000 automated analyzer. Cortisol serum concentration was determined
J. Pers. Med. 2023, 13, 586 7 of 14

with the chemiluminescence immunoassay (CLIA) using the Abbott Architect i1000 im-
munoassay analyzer. Statistical analysis was performed during the process of outcome
assessment, and the research participant did not know the analgesia technique performed
in each procedure.

2.5. Evaluation of Respiratory Muscle Strength

The evaluation of respiratory muscle strength, maximum inspiratory pressure (MIP)
and maximum expiratory pressure (MEP) was performed using an analog manovacuometer.
Individual rubber ducts were used with a rigid-plastic diver-type mouthpiece with an
internal diameter of 2 mm and a length of 15 mm. This was performed according to the
method recommended by Black and Hyatt [25]. Evaluations were performed on the day of
admission (preoperative), as well as 4 h and 24 h after the procedure.
The measurements were performed with the patient in a “beach chair” position (head-
board elevated 45 degrees). Initially, they were oriented to breathe closely to the tidal
volume and, after three breaths, patients were asked to perform a maximum forced ex-
piration (residual volume) and then a maximum static inspiratory effort. These methods
required being sustained for 3 s, with nasal occlusion, in order to obtain the MIP. Subse-
quently, to measure the MEP, the patient breathed at a level close to the tidal volume for
three cycles and performed a maximum inspiration effort (total lung capacity), followed by
a maximum static expiratory effort sustained for 3 s [26]. Both maneuvers were repeated
three times and paired with a one-minute interval in which the highest value obtained
was recorded. For both maneuvers, the patients took three measurements for improved
reproducibility. All measurements were made by the same researcher, who was careful to
maintain the same pattern of verbal commands.

2.6. Statistic Analysis

In the present study, 56 patients were recruited. After applying selection criteria,
51 patients were included into the analysis. One participant was excluded because of spinal
deformity, two were excluded because of high BMI > 40 and two others refused to take the
respiratory tests.
Study power analysis was calculated post hoc. Power calculation was performed for
the variables of Pain 24 h after procedure and MEP 4 h after procedure, which showed the
statistical significance between groups. The test power for the Pain 24 h was equal to 0.962.
As for the MEP 4 h, the resulting power was 0.773. Thus, it is considered that the power of
the study was 0.773, considering the minimum power calculated, and a confidence level of
95% was attained (α = 0.05).
The t test was chosen for quantitative variables whose data presented normal distribu-
tions through the Shapiro test, both for the control and intervention groups, and where the
variances between the groups were considered homogeneous when applying the Bartlett
test. The central trend measure used to perform the t test is the mean of the groups.
For the quantitative variables that, through the Shapiro test, did not present normal dis-
tributions for the control and intervention groups, the test chosen was the Mann–Whitney
nonparametric test. The central trend measure used to perform the Mann–Whitney test
was the median of the groups.
In considering the qualitative or categorical variables, the test chosen was the non-
parametric Chi-square test, which takes into account that the control and intervention
groups are independent.
The R software 4.0.3 version was selected to perform the hypothesis tests between the
patients in both groups, and the Mann–Whitney test was applied to compare each variable
between the groups.
J. Pers. Med. 2023, 13, 586 8 of 14

3. Results
There were 51 patients enrolled in the study. The two groups were similar regarding
age, BMI and comorbidities. No complications were observed, and there were no mortalities
(Table 1).

Table 1. Demographics data of the study. BMI = body mass index; ASA = American Society of
Anesthesiology Status; SD = standard deviation; * chi-square test, ** Mann–Whitney test.

Patients Control Intervention

p Value
(n = 51) (n = 26) (n = 25)
Age (years)
mean (± SD) 50.5 (±13.7) 53.2 (±13.0) 47.7 (±14.1) 0.163 **
Sex
n (%)
Female 38 (74.5) 18 (69.2) 20 (80.0) 0.575 *
Male 13 (25.5) 8 (30.8) 5 (20.0)
BMI (kg/m2 )
mean (± SD) 26.9 (±6.5) 27.46 (±7.1) 26.4 (±6.2) 0.888 **
ASA
n (%)
ASA I 18 (35.3) 8 (30.8) 10 (40.0) 0.692 *
ASA II 33 (64.7) 18 (69.2) 15 (60.0)

3.1. Postoperative Pain and Opioid Usage

A chi-square hypothesis test was performed for the POP variable, and the VAS of pain
score 24 h after the procedure. There was a statistical difference between the control and
intervention groups (p value = 0.0008). There was no statistically significant difference in
the VAS scores obtained 1 h and 4 h after procedure between the control and intervention
groups (Table 2).

Table 2. POP Values. POP = postoperative Pain; * chi-square test.

Control Intervention
POP p Value *
(n = 26) (n = 25)
1 h after procedure 2/4/10/10 4/11/5/5 0.0644
Painless/Light/Moderate/Severe
4 h after procedure 7/12/7/0 11/13/1/0 0.0668
Painless/Light/Moderate/Severe
24 h after procedure 11/14/1/0 23/2/0/0 0.0008
Painless/Light/Moderate/Severe

We found no significant difference regarding the opioid use between the groups.

3.2. Interleukin 6 (IL-6)

When analyzing the three time points in both groups (before the procedure, 4 h and
24 h after), IL-6 presented lower values preoperatively, but 4 h after, IL-6 levels were higher
than 24 h after the procedure. Within the control group, there was a high variability of IL-6
for patients 4 h after the procedure. The dispersion values calculated for all the groups
was 1.0146, with a value of 1.1130 for control, and for intervention the value was 0.8578
(Table 3).
J. Pers. Med. 2023, 13, 586 9 of 14

Table 3. IL-6 values. IL-6 = Interleukin 6; IQR = interquartile range; * Mann–Whitney test.

IL-6 Patients Control Intervention

p Value *
Median (IQR) pg/mL (n = 51) (n = 26) (n = 25)
Before the procedure 1.6 (0.9) 1.7 (0.8) 1.5 (1.2) 0.952
4 h after procedure 59.9 (76) 65.8 (81.8) 59.9 (63.7) 0.744
24 h after procedure 21.6 (28.5) 23.6 (26.1) 20.1 (29.1) 0.877

3.3. Cortisol
Observing the median values for the cortisol variable, the highest median found was
22.2 for the control group at 4 h after the procedure. The lowest median found was 9.8 for
the intervention group measured preoperatively. According to the p values presented in
Table 4, there was no statistical difference for the times before the procedure, 4 h after the
procedure or 24 h after the procedure for the cortisol variable.

Table 4. Cortisol Values. IQR = interquatile range; * Mann–Whitney test.

Cortisol Patients Control Intervention

p Value *
Median (IQR) mcg/dL (n = 51) (n = 26) (n = 25)
Before the procedure 10.4 (8.1) 10.7 (10.4) 9.8 (5.9) 0.720
4 h after procedure 20.7 (19.8) 22.2 (16.95) 18.5 (17.7) 0.205
24 h after procedure 13.3 (9.7) 11.8 (9.7) 14.4 (8.9) 0.275

3.4. C-Reactive Protein (CRP)

The measurement of CRP medians during the preoperative and postoperative periods
did not show many alterations between the intervention and the control group, having the
following values: before the procedure (Control = 2/Intervention = 2); 4 h after procedure
(Control = 3/Intervention = 4); and 24 h after procedure (Control = 36.15/Intervention = 39.65)
(Table 5).

Table 5. C-Reactive Protein t test Results. SD = Standard Deviation.

Variable Mean (SD) Control Intervention p Value

CRP mg/L
Before procedure 2.00 (2.90) 2.00 (6.52) 0.617
4 h after procedure 3.00 (4.24) 4.00 (5.60) 0.962
24 h after procedure 39.48 (22.77) 45.94 (22.45) 0.327

3.5. Respiratory Function

We observed that the MEP measurement, 4 h (Control = 47.5/Intervention = 65) and
24 h (Control = 62.5/Intervention = 70) after the procedure showed a greater difference
between the medians of the intervention in relation to the control Group compared to the
preoperative period (Control = 85/Intervention = 80). Similarly, the MIP measurement, 4 h
(Control = 35/Intervention = 40) and 24 h after the procedure (Control = 45/Intervention = 55)
showed a difference between the medians of the intervention compared to the control group
in relation to the preoperative period (Control = 67.5/Intervention = 60) (Table 6).
J. Pers. Med. 2023, 13, 586 10 of 14

Table 6. MEP and MIP t test results. SD = standard deviation.

Variable Mean (SD) Control Intervention p Value

MEP
Before procedure 86.92 (17.89) 81.00 (19.36) 0.262
4 h after procedure 49.23 (19.01) 63.80 (23.01) 0.017
24 h after procedure 62.50 (21.64) 70.00 (20.36) 0.124
MIP
Before procedure 69.23 (19.42) 61.20 (14.16) 0.097
4 h after procedure 35.00 (18.86) 40.00 (14.49) 0.166
24 h after procedure 45.00 (19.66) 55.00 (12.88) 0.050

4. Discussion
The triad of hypnosis, immobility and antinociception, necessary at the moment of
anesthesia, is achieved through the synergism of different medications. General anesthesia
can inhibit the activity of the central nervous system, reducing surgical trauma to the body,
but it has no significant inhibitory effect on the noxious stimulation signal of the somatic
nerve or on ascending sympathetic nerve transmission.
Strategies to control the neuroinflammatory response to trauma are needed, among
which pharmacological interventions are required, especially minimally invasive surgery
and neural block techniques [27]. This study evaluated a relatively new neural block
technique, which is the anterior QLB approach with promising analgesic coverage, which
has been demonstrated in previous clinical trials of local anesthetic dispersion [28,29].
Currently, QLB is performed as one of the perioperative pain control procedures for all
generations (pediatrics, pregnant women and adults) in abdominal surgery. However,
disagreement persists over the best approach with which to administer the blockade, the
mechanisms action, and the nomenclature [28,30].
Anterior QLB in this study was performed after the induction of anesthesia due to the
time of the plasma peak of Ropivacaine, which is on average 40 min, aiming for greater
safety and greater efficacy of the blockade at the end of the procedure. The blockade
was performed bilaterally, requiring careful consideration of patient positioning and the
calculation of the toxic dose of the local anesthetic.
The fascial planes in the abdominal compartment follow the QL and PM, medially and
laterally, through the arcuate ligaments and the aortic hiatus of the diaphragm, forming the
endothoracic fascia. This provides a potential route of dissemination of the local anesthetic
from the abdominal cavity to the thoracic cavity and paravertebral space, thus achieving
clinical effects [31,32]. In addition to serving as a conduit for local anesthetic spread into the
thoracic paravertebral space, the thoracolumbar fascia, which has a high-density network of
sympathetic fibers as well as mechanoreceptors, is believed to be another major component
responsible for the QLB effects [33].
The majority of authors agree that QLB has an outstanding analgesic effect on pain,
reducing it to scores of 1–2/10 as assessed by VAS, and this usually lasts for more than 24 h.
Patients who receive QLB as part of postoperative pain therapy have lower pain levels both
when resting and moving, which is important for early mobilization. The analgesic effect is
as good as the one achieved by opioids, and there are no unwanted opioid effects such as
nausea and vomiting [34].
According to prospective studies published by Blanco, Ansari & Girgis [28], in 2015
and 2016, the need for morphine has been significantly reduced postoperatively in patients
who received paracetamol, NSAID, and QLB as part of the multimodal postoperative anal-
gesia compared to patients who received only paracetamol and NSAID but did not receive
QLB. Comparative studies have shown that the QLB covers a topographically broader field
(Th7–Th12, compared to TAP Th10–Th12) and yields a prolonged pain-free condition com-
pared to the TAP block (24–48 h for QLB versus 8–12 h for the TAP block) [35–37].
J. Pers. Med. 2023, 13, 586 11 of 14

QLB provides early and rapid pain relief in a high percentage of patients and allows
early ambulation, which is one of the most important measures in the prevention of deep
vein thrombosis and thromboembolic complications [20].
Pain is entirely subjective and its links with pathology are indirect; the only way to
successfully assess pain is to believe the patient. In this study, pain was evaluated utilizing
the VAS. This method is more preferred by patients for its simplicity as well as in its greater
sensitivity in comparison to other pain scales in calculating the pain intensity changes that
occur [38,39].
Metanalysis exhibited several superiorities of QLB for patients undergoing laparo-
scopic surgeries. The results indicated that application of QLB was associated with a
smaller number of patients requiring additional analgesia, with reduced intraoperative
opioid consumption and postoperative opioid consumption, and with lower incidences of
postoperative nausea and vomiting (PONV) compared to placebo [38]. In contrast, Vamnes,
Sorenstua, Solbakk, Sterud, and Leonardsen [39] concluded that preoperative anterior QLB
for laparoscopic cholecystectomy does not affect postoperative opioid requirements and
pain, but that it may decrease PONV.
This study demonstrated a significant reduction in pain scores and opioid consump-
tion in the intervention group (p value < 0.05) and, as demonstrated in two randomized
controlled trials, that QLB reduces cumulative opioid consumption for 48 h after caesarean
section [40,41]. Santos, Rabelo, Borges, Silva, and Silva [42] observed that, after laparo-
scopic cholecystectomy, there was significant reduction in respiratory muscle strength on
the first postoperative day in relation to the preoperative period, with reductions in the
MIP and MEP, despite the laparoscopic surgery causing less pulmonary compromise than
conventional surgery. Our study showed less reduction in pulmonary pressures in the
intervention group in relation to the control group at 4 and 24 h after surgical procedure. Pa-
tients treated with the anterior QLB recovered preoperative muscle strength early, which is
an important result, since anesthesia aims at reducing the repercussions of surgical trauma
and facilitating an early return to function. The early recovery of lung function in patients
undergoing QLB may be related to the optimization of analgesia with this technique.
During surgery, an immune/inflammatory response is initiated, determining varying
degrees of clinical implications. A study of elderly patients concluded that QLB could
improve postoperative cognitive function in this group undergoing laparoscopic radical
gastrectomy. This may be related to the suppression of the inflammatory response after
surgery. Compared with the control group, HMGB1, TNF-α and IL-6 levels were signifi-
cantly decreased 1 and 3 days after surgery in the intervention group (p < 0.05) [43]. Our
research team carried out systematic review of the main biomarkers related to the inflamma-
tory response to surgical trauma in order to define the most sensitive and specific marker
for this research. We did not find in the literature a protocol for evaluating the inflammatory
response to surgical trauma. Thus, we emphasize the importance of standardizing dosages
and collection intervals for future research.
According to the literature, CRP was the most described biomarker, followed by the
IL-6 and TNF-a responses to surgical intervention. IL-6 rose 1 h after surgery with a plasma
peak at 4 to 6 h. CRP starts its rise from 4–6 h (induced by IL-6) with a plasma peak at 48 h.
Although both IL-6 and CRP reflect similarly the magnitude of trauma, the kinetics of these
biomarkers are not identical. When analyzing the IL-6 variable at the three time points, a
high variability among patients 4 h after the procedure was observed within the control
group. It was confirmed via the coefficient of variation calculations that the dispersion of
the IL-6 variable was greater in the control than in the intervention group. This reduction in
the coefficient of variation may demonstrate an attenuation of the immune/inflammatory
response to surgical trauma in the group submitted to anterior QLB. In a study by Zhu,
Qi, He, Zhang, and Mei [43], a significant reduction in IL-6 values was demonstrated in
elderly patients.
Regarding CRP levels between the control and intervention group, we noticed sim-
ilar level patterns without many alterations at the times evaluated. In the intervention
J. Pers. Med. 2023, 13, 586 12 of 14

group, there was only a change in plasma kinetics for IL-6, which did not occur with
CRP. The duration of the effect of anterior QLB is about 12–24 h, having a greater effect
the IL-6 kinetics [44]. Cortisol and ACTH intermediates are activated by IL-6 secretion
and are considered acute-phase hormonal reagents to surgical stress. Cortisol secretion
is also associated with the severity of trauma and stress response. Cortisol is expected
to continue to increase many days after surgery, with peak levels approximately 4–6 h
after the incision [45]. Our study showed lower cortisol values within the first 4 h for the
intervention group. Thus, anterior QLB seems to interfere in the hormonal response to
surgical stress in the first 4 h. Significant results were found for reduction in pain scores
(p < 0.05) in the intervention group. The data and dosage of several substances and cellular
components, including some hormones, leukocyte count, inflammatory cytokines and
analysis of T-lymphocyte behavior, may be useful in monitoring for systemic inflammatory
syndrome (SIS) after elective surgeries. However, there are divergences in the results
of some studies, which can be attributed to potential confounding factors related to the
moment of collection and mediator-dosed, intrinsic factors related to the patients, and the
peculiar behaviors of the mediator to be studied.
In our study, the exclusion of ASA Status III patients who have severe systemic
disease with the functional limitations of advanced age, obesity, emergency situations,
and autoimmune diseases and conversion to open surgery were necessary, because such
conditions can alter the inflammatory response. These comorbidities can interfere with the
measurement of biomarkers. The surgical time is directly related to the magnitude of the
trauma. Therefore, we limited the search to elective laparoscopic cholecystectomies that
lasted an average of 2 to 3 h. The team was the same and the same researcher performed all
anesthetic blocks due to their operator-dependent procedures.
Our study had limitations: for the CRP parameter. A longer patient follow-up would
be necessary since the plasma peak of this marker occurs 48 h after the trauma. The cortisol
result may also have interfered with the surgical schedules. Our research was carried out
during the COVID 19 pandemic, when elective surgeries were reduced in hospitals. The
relatively small sample of patients may also have hampered our analysis.

5. Conclusions
There are several studies in the literature which evaluate the QLB effect on the pain
and surgical stress responses. The present clinical trial evaluated the effect of anterior QLB
on the inflammatory response. Our results suggest a reduced inflammatory response to
surgical trauma in cholecystectomy patients. This technique can be an important adjunct
to multimodal anesthesia in minimally inivasive surgical intervention. Additional appli-
cations have been suggested; namely in the upper and lower abdomen and pelvic cavity.
QLB optimizes the control of the neurohumoral response while maintaining excellent lung
function and pain control.
There is great importance of controlling the metabolic and inflammatory response
to surgical trauma. The paradigm shift currently playing out is from patients having
essentially been treated for pain with analgesics, to treating them with neuroinflammatory
treatment. In fact, pain and surgical stress response are closely related. The method
described by the authors of this article., expands the range of therapeutic interventions and
perioperative care available to physicians, delivering improved patient satisfaction and
impacting public health outcomes.

Author Contributions: Conceptualization, V.G.A.B. and G.N.S.; methodology, R.K.A.F.; software,

M.V.P.; validation, V.G.A.B., K.-U.L. and M.V.P.; formal analysis, R.K.A.F.; investigation, M.V.P.;
resources, V.G.A.B. and G.N.S.; data curation, M.V.P.; writing—original draft preparation, V.G.A.B.,
R.K.A.F. and K.-U.L.; writing—review and editing, V.G.A.B., G.N.S. and M.V.P.; visualization; supervi-
sion, R.K.A.F. and K.-U.L.; project administration,. V.G.A.B. and G.N.S.; funding acquisition, V.G.A.B.,
G.N.S. and R.K.A.F. All authors have read and agreed to the published version of the manuscript.
J. Pers. Med. 2023, 13, 586 13 of 14

Funding: This work was supported by the authors. The physical structure and supplies used were
provided by Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro
(UNIRIO), Rio de Janeiro, Brazil.
Institutional Review Board Statement: The study was approved by the Ethics and Research Com-
mittee of Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro
(UNIRIO), with CAAE no. 26859319.90000.5258.
Informed Consent Statement: All patients/participants or their relatives provided their written
informed consent to participate in this study.
Data Availability Statement: The data are contained within the article.
Acknowledgments: All authors agreed to thank Luiz Cláudio (head of the Laboratory of Research on
Immunology and AIDS at GGUH) for storing the samples in appropriate conditions; and the staffs of
the Surgery/Anesthesia Division of University Hospital, for their support in the logistics of surgical
routines and careful patient selection. The direction and employees of the National Laboratory of
Quality Control from Rio de Janeiro who provided support in the dosages of biomarkers of the
research. Additionally, the patients that accepted to participate in this research.
Conflicts of Interest: The authors declare no conflict of interest.

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