Supplementary Online Content 2

Transcription

1 Supplementary Online Content 2 van Meenen DMP, van der Hoeven SM, Binnekade JM, et al. Effect of on demand vs routine nebulization of acetylcysteine with salbutamol on ventilator-free days in intensive care unit patients receiving invasive ventilation: a randomized clinical trial. JAMA. doi: /jama emethods eresults ereferences etable 1. Ventilator Settings and Respiratory Variables etable 2. Nebulization Related Adverse Events This supplementary material has been provided by the authors to give readers additional information about their work.

2 emethods Nebulization technique Nurses were experienced in applying nebulization of drugs in invasively ventilated patients. Nebulization was performed using jet nebulizers or vibrating mesh nebulizers, depending on local availability. Nebulizers were placed in the inspiratory line between the ventilator tubing system at the side of the patient and the Y piece of the tubing system. The nebulizers were placed prior to the heated humidifier or HME filter. The jet nebulizers were powered by pressured air or oxygen at a continuous flow of 3 to 5 L/min. A typical nebulization session lasted 20 to 30 minutes. Standard Care Standard care followed local clinical guidelines and was performed by independent board certified ICU physicians and board certified ICU nurses not involved in the trial. The nurse to patient ratio in the participating centers varied from 1:1 to 1:2, depending on severity of illness. ICU physicians rotated in 24/7 shifts, meaning that there was always an ICU physician present in the ICU. Physician and nursing staffs were encouraged to use lung protective ventilation strategies including the use of low tidal volumes and positive end expiratory pressures adjusted to severity of lung disease, restrictive sedation preferring analgosedation over hypnosedation, and an intravascular fluid protocol preferring a restrictive over a liberal fluid strategy. ICU nurses performed standard airway care, including endotracheal suctioning, and tracheostomy care if applicable. Endotracheal suction was performed only when clinically indicated and according to current guidelines. 1 All patients received humidification (passive or active) of the inhaled air. Infection prevention Infection prevention strategies consisted of frequent oral care (tooth brushing and rinsing of the oral cavity every six hours), head of bed elevation, hand washing, and use of selective decontamination of the digestive tract. 2 Criteria used for nebulization related adverse events Adverse events that were considered related to the nebulization of acetylcysteine or salbutamol included, development of tachyarrhythmia (defined as new onset tachycardia > 120 pulse/min, or any new onset arrhythmia during or shortly after nebulization), agitation (defined as temporary increase in the Richmond Agitation Sedation Scale score +2 during or shortly after nebulization), hypoxemia (defined

3 as a drop in pulse oximetry to below 90% during or shortly after nebulization), dyspnea (as expressed by an awake patient), bronchospasm (defined as wheezing or typical abnormalities of ventilator waves during or shortly after nebulization), apnea (defined as absence of triggering the ventilator for longer than 30 seconds in a patient on assisted ventilation, during or shortly after nebulization), self extubation (defined as accidental removal of the endotracheal tube by the patient during or shortly after nebulization), and vomiting (defined as vomiting during or shortly after nebulization). The nebulization related complications were reported by the nursing and physician staff in the case report form.

4 eresults Nebulization practice A total of 187 patients (41%) in the on demand received either nebulization of acetylcysteine or nebulization of salbutamol; 61 patients (33%) received nebulization of acetylcysteine, 36 patients (19%) received nebulization of salbutamol, and 90 patients (48%), received both. Of 151 patients receiving nebulization with acetylcysteine, in 127 patients (84%) this was started after a median of 3 (IQR, 2 to 5) days because of thick or tenacious secretions; in 24 patients (16%) who started without a reported indication, nebulization with acetylcysteine started after a median of 1 (IQR, 1 to 3) days. Of 126 patients receiving nebulization with salbutamol, in 84 patients (67%) this was started because of bronchospasm after a median of 3 (IQR, 2 to 6) days; in 42 patients (33%) who started without a reported indication, nebulization with salbutamol started after a median of 2 (IQR, 1 to 5) days. Nebulization of acetylcysteine or salbutamol was continued for a median of 2 (IQR, 1 to 4) and a median of 2 (IQR, 1 to 4) days, respectively. A total of 463 patients (99%) in the routine received nebulization of acetylcysteine with salbutamol according to the study protocol. In 10 patients (2%) some nebulizations were withheld without an indication reported, in 4 (1%) patients nebulization was never started due to unknown reasons. Nebulization of acetylcysteine with salbutamol was continued for a median of 4 (IQR, 3 to 9) days.

5 ereferences 1. American Association for Respiratory Care, AARC Clinical Practice Guidelines Endotracheal Suctioning of Mechanically Ventilated Patients With Artificial Airways Resp Care. 2010;55: Oostdijk EAN, Kesecioglu J, Schultz MJ, et al; Notice of Retraction and Replacement: Oostdijk et al. Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial. JAMA. 2014;312(14): JAMA Apr 18;317(15):

6 etable 1. Ventilator Settings and Respiratory Variables On demand nebulization (n = 455) Ventilator settings, median (IQR) Day 1 Day 2 Day 3 Routine P a On demand Routine P a On demand Routine nebulization nebulization nebulization nebulization nebulization (n = 467) (n = 412) (n = 416) (n = 333) (n = 329 FiO 2, % 40 (30 50) 40 (30 50) (30 45) 40 (30 45) (30 45) 40 (30 46).76 Tidal volume, ml/kg PBW 7.1 ( ) 7.2 ( ) ( ) 8.0 ( ) ( ) 7.9 ( ).06 Plateau airway b pressure, cm H 2 O 19 (16 24) 20 (16 25) (15 23) 18 (15 23) (14 22) 18 (15 22).58 Positive end expiratory pressure, cm H 2 O 8 (5 10) 8 (5 10).39 8 (5 10) 8 (5 10).31 8 (5 10) 8 (5 10).06 Respiratory rate, breaths/min 19 (15 22) 19 (15 24) (15 23) 18 (14 24) (15 24) 20 (15 26).05 Blood gas analysis results, median (IQR) c PaO 2 to FiO 2 ratio 257 ( ) 241 ( ) ( ) 243 ( ) ( ) 229 ( ).59 PaO 2, mmhg 92 (76 112) 90 (77 111) (74 102) 86 (74 99) (71 98) 84 (71 98).82 PaCO 2, mmhg 38 (34 43) 40 (35 44) (35 44) 40 (35 44) (35 44) 39 (36 44).83 Arterial ph 7.38 ( ) 7.36 ( ) ( ) 7.39 ( ) ( ) 7.42 ( ).26 Bicarbonate, mmol/l 22 (20 25) 22 (19 25) (21 26) 24 (21 26) (23 28) 25 (22 28).61 Mode of invasive ventilation, No. (%) d Volume assist 42/392 (10.7) 34/394 (8.6).32 18/367 (4.9) 16/377 (4.2).65 7/277 (2.5) 4/279 (1.4).35 controlled ventilation Pressure assist 74/392 (18.9) 71/394 (18.0).75 50/367 (13.6) 46/377 (12.2).57 31/277 (11.2) 29/279 (10.4).76 controlled ventilation Spontaneous breathing 178/392 (45.4) 160/394 (40.6) /367 (58.3) 225/377 (59.7) /277 (64.6) 181/279 (64.9).94 ventilation Combined controlled spontaneous ventilation 98/392 (25.0) 129/394 (32.7).02 85/367 (23.2) 90/377 (23.9).82 60/277 (21.7) 65/279 (23.3).65 Abbreviations: FiO 2, fraction of inspired oxygen; IQR, interquartile range; PaO 2, partial pressure of arterial oxygen; PaCO 2, partial pressure of arterial CO 2; PBW, predicted body weight. a P-values are not corrected for multiple testing. b Or maximum airway pressure with pressure controlled ventilation. c In case of more than one blood gas analysis per day, the result closest to 6 AM was used. d Mode of invasive ventilation was not complete for all patients. P a

7 etable 2. Nebulization-Related Adverse Events a On demand nebulization Routine nebulization Patients with acetylcysteine only (n = 61) Patients with salbutamol only (n = 36) Patients with acetylcysteine and salbutamol (n = 90) Patients with acetylcysteine and salbutamol (n = 463) Events No. /n (%) b 20/61 (32.8) 7/36 (19.4) 36/90 (40.0) 147/463 (31.7) Tachyarrhythmia c 18/61 (29.5) 6/36 (16.7) 33/90 (36.7) 121/463 (26.1) Agitation d 1/61 (1.6) 0/36 (0.0) 0/90 (0.0) 20/463 (4.3) Hypoxemiae 1/61 (1.6) 1/36 (2.8) 7/90 (7.8) 20/463 (4.3) Dyspnea f 0/61 (0.0) 0/36 (0.0) 1/90 (1.1) 5/463 (1.1) Bronchospasm g 1/61 (1.6) 0/36 (0.0) 0/90 (0.0) 4/463 (0.9) Apnea h 0/61 (0.0) 0/36 (0.0) 0/90 (0.0) 3/463 (0.6) Self extubation i 0/61 (0.0) 0/36 (0.0) 0/90 (0.0) 4/463 (0.9) Vomiting j 0/61 (0.0) 0/36 (0.0) 1/90 (1.1) 6/463 (1.3) a Adverse events during and within the first hour after start of nebulization. b Proportion of adverse events presented by type of administered nebulization (acetylcysteine, salbutamol, or combined). Patients could have developed more than one different nebulization related adverse event. If a patient experienced the same event more than once, only one event was counted. c New onset tachycardia > 120 pulse/min, or any new onset arrhythmia during or shortly after nebulization d A temporary increase in the Richmond Agitation Sedation Scale score +2 during or shortly after a nebulization. e A drop in pulse oximetry to below 90% during or shortly after nebulization. f As expressed by an awake patient during or shortly after nebulization. g Wheezing or typical abnormalities of ventilator waves during or shortly after nebulization. h Absence of triggering the ventilator for longer than 30 seconds in a patient on a spontaneous breathing mode during or shortly after nebulization. i Accidental removal of the endotracheal tube by the patient during or shortly after nebulization. j Vomiting during or shortly after nebulization.