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 FEV1 > 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 forin each intercostal space: 0) Normalaeration, characterized by thepresence 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 thepresence 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, 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,

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,

References

1.von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007;370(9596):1453-1457.

2.Esteban A, Alia I, Tobin MJ, et al. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med 1999;159(2):512-518.

3.Bouhemad B, Liu ZH, Arbelot C, et al. Ultrasound assessment of antibiotic-induced pulmonary reaeration in ventilator-associated pneumonia. Crit Care Med 2010;38(1):84-92.

4.Bouhemad B, Zhang M, Lu Q, et al. Clinical review: Bedside lung ultrasound in critical care practice. Crit Care 2007;11(1):205.

5.Lichtenstein D, Meziere G, Biderman P, et al. The comet-tail artifact. An ultrasound sign of alveolar-interstitial syndrome. Am J Respir Crit Care Med 1997;156(5):1640-1646.

6.Lichtenstein DA, Lascols N, Meziere G, et al. Ultrasound diagnosis of alveolar consolidation in the critically ill. Intensive Care Med 2004;30(2):276-281.

7.Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification. Eur J Echocardiogr 2006;7(2):79-108.

8.Bouhemad B, Nicolas-Robin A, Arbelot C, et al. Isolated and reversible impairment of ventricular relaxation in patients with septic shock. Crit Care Med 2008;36(3):766-774.

9.Bouhemad B, Nicolas-Robin A, Benois A, et al. Echocardiographic Doppler assessment of pulmonary capillary wedge pressure in surgical patients with postoperative circulatory shock and acute lung injury. Anesthesiology 2003;98(5):1091-1100.

10.Garcia MJ, Ares MA, Asher C, et al. An index of early left ventricular filling that combined with pulsed Doppler peak E velocity may estimate capillary wedge pressure. J Am Coll Cardiol 1997;29(2):448-454.

11.Schisterman EF, Perkins NJ, Liu A, et al. Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples. Epidemiology 2005;16(1):73-81.

12.Ray P, Le Manach Y, Riou B, et al. Statistical evaluation of a biomarker. Anesthesiology 2010;112(4):1023-1040.