Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05906030 |
| Other study ID # |
K2023-3473 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2023 |
| Est. completion date |
September 1, 2027 |
Study information
| Verified date |
June 2023 |
| Source |
Karolinska University Hospital |
| Contact |
Jessica Kåhlin, MD, PhD |
| Phone |
0707295456 |
| Email |
jessica.kahlin[@]regionstockholm.se |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This study aims at determining whether diaphragm ultrasound examining diaphragm thickening
fraction, excursion and density before and after surgery can predict respiratory
complications in the postoperative period.
Patients scheduled for major elective abdominal, pelvic or vascular surgery will be included
in the study and diaphragm ultrasound is performed before surgery and after surgery in the
postoperative ward. Physiological parameters, laboratory parameters, data on surgery and
anesthesia and comorbidities will be registered. Complications such as pneumonia,
desaturation, need for intubation and other respiratory events up to 30 days will be
registered and later correlated with the diaphragm measurements.
Description:
Background
A considerable part of the population undergo surgery every year and in Sweden around 600,000
surgeries are registered yearly. Occurring complications after surgery include wound
infections, urinary tract infections, venous thromboembolism and pneumonia. Postoperative
pneumonia is the third most common complication and increases morbidity and mortality
substantially(1). Furthermore, it prolongs hospital length of stay (LOS), increases medical
costs and hospital readmissions. The incidence of postoperative pneumonia is dependent on
non-modifiable factors such as type of surgery, age, sex and preoperative functional status
but also on modifiable factors like smoking and adherence to preventive bundles(2). However,
pneumonia preventive bundles are more studied and used in the ICU than in the perioperative
setting. The current burden of postoperative pneumonia in Sweden is presently unknown.
Furthermore, few prognostic examinations and preventive measures are used in the
perioperative setting. It is well known that diaphragm dysfunction affects patients after
major abdominal surgery and that it affects outcome postoperatively(3, 4). The mechanism
behind the diaphragm dysfunction is unclear but animal studies indicate that postoperative
inflammation may weaken the diaphragm only hours after exposure(5). Postoperative respiratory
complications are partly due to a deteriorated diaphragm function and cause increased
morbidity and mortality(6). In cardiac and upper abdominal surgery patients, ultrasound
measurements of diaphragm excursion and thickening proved useful in ruling out diaphragm
dysfunction(7, 8).
Diaphragm dysfunction can be diagnosed using ultrasound measuring diaphragm excursion,
diaphragm thickness, thickening or diaphragm density. The examinations have high intra- and
inter-observer reliability, are non-invasive and non-ionizing imaging techniques. This is in
sharp contrast to twitch magnetic phrenic nerve stimulation, the golden standard technique
for measuring diaphragm function, being reliable but invasive(9). Electric impedance
tomography (EIT) is a non-invasive radiation-free imaging technique that provides real-time
images and data of regional lung ventilation and lung volumes (10) and the correlation to
diaphragm dysfunction and the later development of atelectases as assessed with ultrasound of
the diaphragm is not clear. Furthermore, parameters on lung volumes retrieve with spirometry
also lack a clear relationship with diaphragm ultrasound parameters and later respiratory
complications.
Diaphragm ultrasound has previously been used to identify severe dysfunction. However, to
identify early signs of dysfunction could render important actions perioperatively to avoid
progression and continuation of early diaphragm dysfunction and hence an increased risk of
complications.
Gap of knowledge Can diaphragm ultrasound in the peroperative setting predict respiratory
complication after dismissal from postoperative ward? And can diaphragm dysfunction as
defined with ultrasound be correlated to changes in lung volumes and lung function as
demonstrated with EIT and spirometry?
Hypothesis We hypothesize that diaphragm ultrasound parameters indicating diaphragm
dysfunction can predict respiratory complications in the perioperative setting.
Aims Overall aim To perform a comprehensive mapping of respiratory complications in the
perioperative setting and to determine whether diaphragm dysfunction determined with
diaphragm ultrasound can aid in predicting respiratory complications after major surgery.
Specific aims
1. To determine whether attenuated diaphragm function measured with diaphragm ultrasound
before and after major elective abdominal, pelvic or vascular surgery can predict
respiratory complications at 30 days.
2. To determine whether attenuated diaphragm function measured with diaphragm ultrasound
before and after major acute abdominal, pelvic or vascular surgery can predict
respiratory complications at 30 days.
Primary endpoint Pneumonia in the first postoperative week in relation to reduced diaphragm
function.
Secondary endpoints Desaturation <90% in the postoperative ward or in the ward, takypnea >30
breaths/minute in the postoperative ward or in the ward, PaO2<9 in the postoperative ward,
PaCO2>7 in the postoperative ward, need for intubation, need for non-invasive ventilation
(NIV).
Design of study Prospective non-randomized observational study
Inclusion criteria
1. Adult, ≥18 years old
2. Planned for elective (study 1) or acute (study 2) abdominal, vascular or pelvic surgery
at Karolinska University Hospital, Solna during the study period
Exclusion criteria
1. Chronic lung disease
2. Patients incapable of giving consent
3. Pregnancy
Methods
Patients 18 years and older undergoing open abdominal, pelvic or vascular surgery at the
Karolinska University Hospital will be examined with diaphragm ultrasound measuring diaphragm
excursion, thickness and density before surgery and before discharge from the postoperative
ward. Respiratory complications up to 30 days after surgery will be recorded from the
patients´ charts and correlated with the ultrasound parameters.
1. In a first study elective abdominal, pelvic or vascular surgery patients will be
examined with diaphragm ultrasound preoperatively and (2-3 times) at the postoperative
unit. The patients will be observed at the ward with regards to pulseoximetry, need for
oxygen, vital parameters etc. These parameters will be correlated with registered
respiratory complications at 30 days.
2. In a second study, acute abdominal, pelvic or vascular surgery patients will be examined
with diaphragm ultrasound, preoperatively (on the operating table before anesthesia) and
(2-3 times) at the postoperative unit and subsequently observed at the ward with regards
to pulseoximetry, need for oxygen, vital parameters etc. Retrieved parameters will be
correlated with registered respiratory complications at 30 days.
Prior to these studies the method will be validated according to standards.
The examination of the diaphragm will be performed with the ultrasound machines normally used
at the units. A curved transducer with the frequency 2,5-3,5 MHz or a linear transducer with
the frequency 7,5-10 MHz is placed in the supine position at the right and left costal arch
measuring the movement of the diaphragm at inspiration, the thickening of the diaphragm at
inspiration and the diaphragm density. The examination is pain-free, non-invasive,
non-radiating and takes about 15 minutes.
1. Diaphragm excursion:
The movement of the diaphragm at inspiration is measured with a convex/curved
transducer. On the right side, the probe is placed between the mid-clavicular line and
the anterior axillary line under the costal arch. The probe is angled medially,
cranially and dorsally to hit the diaphragm cupola in a perpendicular manner. The
displacement of the diaphragm with inspiration is measured and registered in M-mode.
2. To measure diaphragm thickening the probe is placed between the 8:th and 9:th rib
between the antero- and midaxillary line. The right diaphragm curvature is found 0,5-2
cm beneath the phrenicocostal sinus. M-mode is used to measure the thickness from the
pleural line to the peritoneal line at forced residual capacity (FRC) and total lung
capacity (TLC), I e at maximal inspiration. Normal thickening is 2,7mm +-0.5 mm and
values under 2mm (<20%) are considered pathological.
3. Diaphragm density is measured in B-mode whereby a grayscale histogram is created with a
special software (Image J or similar). The density is measured in percent of a grayscale
where a value >65% (based on grayscale histograms on healthy controls) is defined as
pathological.
The examination of the diaphragm will be performed pre-operatively on the operating ward.
Postoperatively, the patient is examined on the operating table if possible and at two more
occasions on the postoperative ward.
On the postoperative ward, the patient's vital functions are monitored and this data will be
registered in the CRF (saturation, pulse, blood pressure, breathing frequency, pain
estimation). Data on medications, anesthetics, surgery time, anesthesia time, perioperative
bleeding, fluid balance, When the patient is transferred to the ward, a member of the
research group will perform a follow-up ultrasound 24-72h after the first ultrasound. At this
timepoint, vital parameters, data on medications, fluid balance and complications will be
registered.
The patient will thereafter be followed up in Take Care (and Clinisoft if admitted to the
ICU) with regards to respiratory complications up to 30 days after the initial surgery.
Data from the diaphragm ultrasounds will be saved in the ultrasound machine and exported as
both pictures and numerical files to pass word-protected hard disks.
Statistics Comparison of the primary outcome will be analysed with the Pearson chi-square
test or two-tailed Fisher exact test for each diaphragm parameter. Baseline patient
characteristic data will be described, and secondary outcomes, as described above, will be
analysed as appropriate, depending on categorical or continuous parameters and normal or
non-normal distribution. Data will be presented as mean ± SD or 95% CI, as median and range
or numbers (%) dependent on the above.
Clinical relevance
This project will perform a unique mapping of the magnitude of postoperative complications
after major surgery in Sweden. Several studies demonstrate diaphragm weakness after major
surgery which predisposes the patient to respiratory complications postoperatively. Early
detection of diaphragm weakness in the perioperative setting would give an opportunity to
prevent respiratory complications by introducing pneumonia bundles, physiotherapy and
increase awareness of symptoms of complications. Postoperative respiratory complications
impose great challenges on the individual´s recovery as well as on health care costs. To
introduce a non-invasive, reliable, cheap and painless diagnostic tool that could aid in the
prevention of such complications would reduce both burden of illness and costs related to
surgery.
References
1. Kazaure HS, Martin M, Yoon JK, Wren SM. Long-term results of a postoperative pneumonia
prevention program for the inpatient surgical ward. JAMA Surg. 2014;149(9):914-8.
2. Chughtai M, Gwam CU, Mohamed N, Khlopas A, Newman JM, Khan R, et al. The Epidemiology
and Risk Factors for Postoperative Pneumonia. J Clin Med Res. 2017;9(6):466-75.
3. Ford GT, Whitelaw WA, Rosenal TW, Cruse PJ, Guenter CA. Diaphragm function after upper
abdominal surgery in humans. The American review of respiratory disease.
1983;127(4):431-6.
4. Berdah SV, Picaud R, Jammes Y. Surface diaphragmatic electromyogram changes after
laparotomy. Clin Physiol Funct Imaging. 2002;22(2):157-60.
5. Krause KM, Moody MR, Andrade FH, Taylor AA, Miller CC, 3rd, Kobzik L, et al. Peritonitis
causes diaphragm weakness in rats. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1277-82.
6. Sasaki N, Meyer MJ, Eikermann M. Postoperative respiratory muscle dysfunction:
pathophysiology and preventive strategies. Anesthesiology. 2013;118(4):961-78.
7. Lerolle N, Guérot E, Dimassi S, Zegdi R, Faisy C, Fagon JY, et al. Ultrasonographic
diagnostic criterion for severe diaphragmatic dysfunction after cardiac surgery. Chest.
2009;135(2):401-7.
8. Kim SH, Na S, Choi JS, Na SH, Shin S, Koh SO. An evaluation of diaphragmatic movement by
M-mode sonography as a predictor of pulmonary dysfunction after upper abdominal surgery.
Anesth Analg. 2010;110(5):1349-54.
9. Doorduin J, van Hees HW, van der Hoeven JG, Heunks LM. Monitoring of the respiratory
muscles in the critically ill. Am J Respir Crit Care Med. 2013;187(1):20-7.
10. Lobo B, Hermosa C, Abella A, Gordo F. Electrical impedance tomography. Ann Transl Med.
2018;6(2):26.
