EXPANDED ONLINE Methods
The study was performed in the ICU of the University Hospital “Maggiore della Carità” in Novara (Italy), between December 2008 and December 2009, according to the principles outlined in theDeclaration of Helsinki. The protocol was approved by the local Ethics Committee,and written informed consent was obtained for all patients.
Patients
26 consecutive patients were enrolled into the study protocol, but only 24 were included in the data analysis. Patients were assigned to the BL or UL according to the distribution of lung collapse to reach a total number of 12 consecutive patients per group as indicated by the power analysis. 2 BL patients enrolled were excluded, as they did not end the protocol for intolerance. After inclusion of the 24 patients, a further group of 7 consecutive BL patients was evaluated in order to ascertain whether or not a carry-over effect secondary to time-dependent alveolar recruitment took place.The inclusion criteria were: PaO2/FiO2 300while breathing through a Venturi mask (VMASK) withnominalFiO2 ≥ 40%, and dyspnea and accessory muscles activation at rest.
The presence of UL or BL lung consolidation, as definedin previous studies[1,2]according to the Fleischner Society glossary[3],was determined from the chest x-ray, which was independently evaluated by 1 radiologist and 2 ICU physicians working at the same institution. Each physician indicated whether the UL or BL classification was definite, probable, or doubtful. Patients were classified as having UL or BL when all 3 physicians agreed on definite or probable UL or BL. By protocol patients who met neither the criteria for ULnor BL were excluded, but this never happened.
Patients were excluded from the study whenever they met one of the following criteria: 1) PaCO2 ≥ 50 mmHg and pH < 7.35; 2) Glasgow Coma Score ≤ 10; 3) hemodynamic instability, i.e., systolic arterial pressure < 90 mmHg despite fluid repletion, 4) use of vasoactive agents, i.e., vasopressin, epinephrine and norepinephrine at any dosage, and dopamine or dobutamine > 5 µg/kg/min; 5) need for emergency intubation and cardio-pulmonary resuscitation; 6) life threatening arrhythmia or myocardial ischemia; 7) cardiogenic pulmonary edema;8) chronic obstructive pulmonary disease (COPD); 9) more then 2 organ dysfunctionsin addition to h-ARF[4];10) recent esophageal, neck, facial, or head surgery or trauma; 11) body mass index > 30 kg/m2; 12) claustrophobia; 13) unmanageable copious secretions, 14) need for sedation, 15) enrollment in other research protocols.
Criteria for study interruption
Predetermined criteria for immediate n-CPAP interruption were: 1) cardiac or respiratory arrest; 2) inability to protect the airway; 3) inability to clear secretions; 4) inability to maintain peripheral oxygen saturation (SpO2) ≥ 90% with a FiO2 ≤ 60%; 5) uncontrolled vomiting; 6) altered sensorium (obnubilation or psychomotor agitation);7) hemodynamic instability, or life-threatening arrhythmias or cardiac ischemia; 8) patient’s intolerance to helmet.
Instrumentation and settings
Patients received n-CPAP through a noninvasive ventilation (NIV)-helmet (CaStar®, StarMed, Mirandola, Modena, Italy) by means of a continuous gas flow system. Continuous flow of fresh gas was delivered to the inspiratory port of the helmet at a rate of 40-50 L/min; FiO2was adjusted on an O2/air flow-meter (Flow-Meter, StarMed, Mirandola, Modena, Italy). FiO2 was maintained at the same value set with the Venturi mask. PEEP was applied to the expiratory port of the helmet connected to an electromechanical valve inserted between two gas outlets (TwinPAP®, StarMed, Mirandola, Modena, Italy)[5]. One of the 2 gas outlets was connected to a 22 mm adjustable (0-20 cmH2O) spring-loaded PEEP valve, while the other one to a PEEP valve pre-calibrated at 25 cmH2O (StarMed, Mirandola, Modena, Italy). By opening and closing the TwinPAP® valve we were able to apply a recruitment maneuver to n-CPAP by increasing airway pressure from 10 to 25 cmH2O for 8 seconds once a minute (SIGH).
Study design and monitoring
The protocol consisted of four consecutive steps: 1) 30 minutes breathing troughVMASK, 2) 1 hour n-CPAP 10 cmH2O via helmet (n-CPAP1), 3) 1 hour n-CPAP 10 cmH2O via helmet + SIGH (n-CPAPSIGH), and 4) 1 hour n-CPAP 10 cmH2O via helmet(n-CPAP2). An additional control group of patients with bilateral lung involvement followed the same protocol, where the third trial was replaced by another n-CPAP 10 cmH2O trial.
Patients maintained the semi-recumbent position throughout the study protocol to continuously ensure correct pneumatic seal of the helmet. Humidification was not provided during the study protocol. Heart rate, systolic and diastolic pressure, and SpO2 were monitored throughout the entire study period. Furthermore, at the end of each protocol step,respiratory rate was determined by visual inspection of the chest, arterial blood was taken for gas analysis, and the patient was asked to score dyspnea on a visual analogic scale (VASdysp), as previously described[6].
The time lag necessary to reach 25 from 10 cmH2O was determined by measuring airway pressure (Paw) and flow through a side-port and a pneumotachograph (Fleisch No. 2; Metabo; Epalinges, Switzerland), respectively, both connected to different pressure transducers (Digima Clic-1, ICU-Lab System; KleisTEK Engineering; Bari, Italy), in healthy volunteers breathing through a mouthpiece sited inside the helmet. The signals were amplified, filtered, digitized at 100 Hz, and stored in a personal computer for further analysis. The average time to attain the higher pressure level was 1.9 ± 0.22 seconds.This time span is similar to that found in patients with h-ARF not included in this study (i.e. 1.6 ± 0.67 seconds), in which respiratory mechanics was monitored for clinical purpose, although different respiratory drive and different compliance of the respiratory system might slightly influence these findings.
Statistical analysis
Based on data from previous studies [7,8], we hypothesized that the addition of SIGH to n-CPAP would determine a 40% higher increase in PaO2/FiO2 in BL group as compared to UL, and accordingly calculated an overall sample size of 24 patients (power 80%, 0.05).
Results are expressed as median ± interquartile range or mean ± standard deviation depending on data normality distribution. Two-way Anova analysis of variance for repeated measurements was applied to ascertain differences between the four steps protocol in BL and UL patients; post hoc analysis was performed using the Student-Newman-Keuls, as indicated.P values < 0.05 were considered statistically significant.
Reference List
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