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Ultrasound assessment of lung aeration loss during a successful
weaning trial predicts postextubation distress
Supplemental Digital Content
MATERIAL AND METHODS
This study, in accordance with the recent published STROBE guidelines (1),
was registered by the U.S National Institute of Health in ClinicalTrials.gov as
Identifier NCT01098773. The study was conducted in two multi-disciplinary French
ICUs: a 12-beds ICU “Réanimation Polyvalente Pierre VIARS” (Pr Rouby) in
University Hospital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, and a
16-bed ICU
“Réanimation Polyvalente” (Pr Bazin), Hôpital Estaing, Clermont-
Ferrand. Procedures were standardized between centers.
Inclusion criteria and data collection
Patients mechanically ventilated and equipped with an arterial line were
screened for inclusion when showing clinical improvement of the clinical condition
that had required intubation and invasive mechanical ventilation. Inclusion criteria
were: 1) existence of stables conditions allowing interruption of sedatives drugs for
several hours with a fully awake patients defined as Glasgow coma scale above 13,
2) stable hemodynamic status defined as a mean arterial blood pressure > 65 mmHg
without the use of vasoactive drugs for at least 24 hours 3) adequate gas exchange
defined as a PaO2 > 60 mmHg using FiO2 < 40%, positive end-expiratory pressure <
5 cmH2O, pressure support ≤ 10 cmH20, with a respiratory rate < 25/min and a tidal
volume > 7ml/kg, 4) a core temperature < 38°C, 5) an hemoglobin level > 8g/dL (2).
When fulfilling all criteria, patients were ready to pass a spontaneous breathing trial
(SBT) on T-tube with a deflated endotracheal cuff.
Spontaneous breathing trial success, failure and postextubation distress were
defined as previously described (2). SBT success was defined when patients fulfilled
all the followings criteria: heart rate <130 b/min or variation < 20%, systolic blood
pressure between 90 and 200 mmHg, respiratory rate < 35/min without recruitment of
accessory respiratory muscles, SpO2 > 90% with an O2 supply < 9L/min and
PaCO2< 45 mmHg, an efficient cough, a good neurological status with quiet and
cooperative patient. On the contrary, SBT failure was definied when patient
presented one criteria among the followings: heart rate > 130/min or variation > 20%,
a systolic blood pressure < 90 or > 200 mmHg, a respiratory rate > 35/min or
recruitment of accessory muscles, a SpO2 < 90% with O2 supply >9L/min, a PaCO2 >
45 mmHg or a variation > 25%, an inefficient cough (unable to propel secretions into
the tube), altered consciousness, excessive anxiety, hypercarbia. Postextubation
distress was definied when respiratory failure criteria occurred and required a
resumption of ventilatory support (either non invasive or invasive ventilation) within
48h after extubation. Criteria for re-establishing mechanical ventilation were:
respiratory rate > 35/min or recruitment of accessory muscles, a SpO2 < 90% with O2
supply > 9L/min, a PaCO2 > 45 mmHg with pH < 7.35, an inefficient cough (unable to
propel secretions into the tube), heart rate > 130 b/min or variation > 20%, systolic
blood pressure < 90 or > 200 mmHg, altered consciousness, excessive anxiety and
hypercarbia.
Usual demographics variables were recorded such as age, sex, mode and
reason of admission in the ICU (scheduled or emergency surgery, type of surgery,
medical disease), underlying co-morbidities such as cardiovascular disorders
(coronary artery disease, hypertension, valvulopathy), past history of pulmonary
disease (chronic obstructive pulmonary disease with FEV 1 > 50%, smoking habit,
asthma) and renal impairment. SOFA and SAPS II on admission, length of
mechanical ventilation, body weight on admission and at day of inclusion, fluid
balance over the last 24 hours and since admission were recorded. Respiratory
frequency, heart rate, blood pressure, pulsed-oxygen saturation (SpO2) and level of
consciousness were closely monitored by the nurse during the 60-min SBT.
Lung ultrasound
Lung ultrasound was performed by trained physicians only, using a Siemens
Acuson CV70 or a Philips Envisor with 2-4 MHz probes. As previously
recommended, all intercostal spaces of upper and lower parts of anterior, lateral and
posterior regions of left and right chest (12 region of interest) were carefully and
extensively examined (3-6). Each region of interest was identified according to
anatomical landmarks: from sternum to anterior axillary line for anterior lung regions,
from anterior to posterior axillary lines for lateral lung regions and from posterior
axillary line to spine for posterior lung regions. Upper and lower parts of anterior,
lateral and posterior lung region were determined using the horizontal mamillary line.
Four ultrasound patterns corresponding to different degree of aeration loss were
looked for in each intercostal space: 0) Normal aeration, characterized by the
presence of lung sliding with horizontal “A lines” and, occasionally, 1 or 2 isolated
vertical “B lines”; 1) Moderate loss of lung aeration, characterized either by multiple
well-defined and regularly spaced 7-mm apart “B1 lines”, issued from the pleural line
and corresponding to interstitial edema 2) Severe loss of lung aeration, characterized
by multiple coalescent vertical B2 lines issued from the pleural line and
corresponding to alveolar edema; 3) Complete loss of lung aeration resulting in lung
consolidation and characterized by the presence of tissue pattern containing either
hyperechoïc punctiform images representative of static air bronchograms, or
hyperechoïc tubular images, representative of dynamic air bronchograms. The worst
ultrasound pattern observed in one or several intercostal spaces was considered as
characterizing the region of interest. A value (0 ,1 ,2 or 3) was attributed to each
region examined and the lung ultrasound score was calculated as the sum of the 12
regions examined (3).
Echocardiography
Echocardiographic measurements were made at the end-expiratory period
over five consecutive cardiac cycles. Transthoracic echocardiography was performed
using a Siemens Acuson CV70 or a Philips Envisor with 2-4 MHz probes. Images
were stored for later playback and analysis. Left systolic function was derived from
left ventricular end-diastolic area (LVEDA) and left ventricular end-systolic area
(LVESA). LVEDA and LVESA were measured on the short axis parasternal view
excluding the papillary muscles at the mid-papillary level) (7). Left ventricular systolic
function was assessed by calculating the fractional area change (FAC), defined as
(LVEDA - LVESA)/LVEDA. A systolic dysfunction was defined by a FAC of < 50%.
The transmitral flow was recorded by pulsed Doppler with the sample volume placed
at the mitral valve tips. The mitral inflow velocity was analyzed for peak velocity of
early (E) and late (A) filling, deceleration time of E (DTE). Velocities of mitral annulus
were recorded by a tissue Doppler imaging (TDI) program with a 5-mm sample
volume placed at the lateral corner of the mitral annulus (8-10). The early diastolic
(Ea) velocity of mitral annular displacement was measured from the TDI recording
and the E/Ea ratio was calculated.
Three arterial samples for blood-gas analysis with BNP were performed
before, at the end of SBT, and if necessary 4H-6H after extubation. B-type Natriuretic
Peptide (pg/mL) were analyzed on a plasma sample stored on EDTA –tube and
obtained after whole lung centrifugation using a TriageO Meter BNP test (BIOSITE).
Statistical Analysis:
Receiver operating characteristic and its area under curve (AUC-ROC)
represents the probability of assigning a greater risk to present a postextubation
distress to a randomly selected patient who failed extubation at H48 compared with a
randomly selected patient who was successfully weaned. The discriminate power of
LUS score was quantified by measuring the area under the receiver-operating
characteristic (AUC ROC), which is the usual global measure of the performance of a
prognostic test. Calibration was assessed by the Hosmer-Lemeshow test. The
determination of the cutoff point to make a clinical appropriate discrimination was
assessed by maximizing the Youden index (11). Since a single cutoff dichotomizes
the population, we completed the analysis and rather propose two cut-offs for
sensibility and specificity above 90%, associated with their respective likelihood
ratios separating an inconclusive limit. This approach is probably more useful from a
clinical point of view with a more fair communication and a better understanding of
the values presented (12). Interval likelihood ratios are calculated with 95%
confidence interval as follows. Positive likelihood ratio is the ratio between the
probability of a positive test result given the presence of the disease and the
probability of a positive test result given the absence of the disease. Negative
likelihood ratio is the ratio between the probability of a negative test result given the
presence of the disease and the probability of a negative test result given the
absence of the disease.
In multivariate analysis, the association of LUS on ICU-mortality or extubation
failure was performed with binaries logistic regression. The odds ratio are given with
their 95% CI.
RESULTS
Predicting factors of spontaneous breathing trial failure and postextubation
distress
Assessment of clinical variable differences during the weaning trial
Changes in oxygen saturation, respiratory rate, arterial CO2 level, and
cardiovascular parameters (cardiac frequency and blood pressure) did not
significantly differ during a successful SBT among patients who develop
postextubation
distress
and
patients
definitively
weaned.
Similarly,
theses
physiological variables were not different between theses two groups before and at
the end of SBT.
Cardiovascular abnormalities during spontaneous breathing trial.
As
shown
in
Figure
S1
(Supplemental
Digital
Content
2,
http://links.lww.com/CCM/A436), BNP changes were significantly correlated to E/Ea
changes only in patients with postextubation distress (r2=0.89).
FigureS1. Variations of E/Ea according to variations of B-type Natriuretic Peptide
(BNP) in patients with postextubation success and postextubation distress. On the y
axis, variations of the ratio between early mitral flow and early diastolic velocity of
mitral annular displacement (E/Ea) during the spontaneous breathing trial are
represented. On the x axis, variations of BNP during SBT are represented. Empty
circles represent patients with postextubation success, and back circles represent
patients with postextubation distress.
Figure S2. Illustration of thoracic scanning points used to perform a LUS according
to anatomical landmarks. Theses anatomical landmarks are depicted as follows: Red
line represents the sternum, Green line represents the horizontal mamillary line,
White line represents the anterior axillary line, Blue line represents the posterior
axillary line (see Supplemental Digital Content 3, http://links.lww.com/CCM/A437).
Lung aeration loss before and during weaning trial.
In a multivariate analysis adjusted on severity scores on admission (SOFA,
SAPS2) and duration of mechanical ventilation before SBT, the end-SBT LUS was
significantly associated to extubation failure with OR=1.41 1.21 – 1.65 , p<0.001 per
LUS unit increase.
Figure S3. Regional changes in lung aeration during the spontaneous breathing trial
(SBT) in 29 patients with postextubation distress. For each patient, ultrasound
changes were assessed in 12 thoracic regions: upper and lower parts of anterior
thoracic regions, upper and lower parts of lateral thoracic regions, and upper and
lower parts of posterior thoracic regions in each lung. A total of 348 regions were
examined twice before and after the SBT. On the y axis, data are expressed as the
percentage of patients demonstrating no change in ultrasound pattern (white bars),
lung derecruitment (black bars) and lung recruitment (grey bars). N= normal aeration,
B1= B lines well defined with irregular spacing, B2= multiple coalescent B lines, C=
alveolar consolidation. On the x axis, the first symbol indicates the ultrasound pattern
before SBT, and the second symbol indicates the ultrasound pattern at the end of
SBT (see Supplemental Digital Content 4, http://links.lww.com/CCM/A438).
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