Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE.

An article on ARDS ventilation with neuromuscular blockade. Reviewed by Jason Duberville. Collin College Respiratory Care Program. Spring 2011.

Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE. Abstract

The New England Journal of Medicine recently published an article regarding early acute respiratory distress syndrome (ARDS). It was noted that ARDS patients receiving sedation with an additional neuromuscular blocker (cisatracurium besylate) had a 31% mortality rate, verses, 40.7% in patients receiving sedation with a placebo. Secondary findings were that pneumothorax occurred in the cisatracurium group at the rate of 4.0%, verses, 11.7% for the placebo group. (Papazian et. al. 2010) This paper reviews ARDS, ventilation details for the study population, and, gives a brief readers critique to fulfill the objectives of course RSPT1361, Clinical II, for the Collin College Respiratory Care Program.

Key words: ARDS, neuromuscular blockers, ventilation.

Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE. Acute Respiratory Distress Syndrome (ARDS) Review. Acute respiratory distress syndrome is commonly referred to as ARDS in medical literature. The term is used to describe a severe condition of fluid within the alveolar space from the capillaries, which have developed abnormal permeability. Terry Des Jardins text on respiratory disease provides a good illustration of ARDS at the alveolar level. (Diagram 1) In addition to fluid, a proteinous film also forms within the alveoli, termed a hyaline

membrane. The hyaline membrane occurs after the first 48 hours of the condition, thought to be caused by myofibroblasts. (Des Jardin 2011) The mortality rate for ARDS is at best near 30 percent, and much usually higher. The high rate is partly due to the pulmonary edema caused by pathological capillary permeability, which resists clearance by diuretics more than common hydrostatic edemas. (Stanford 2011) Fluid overload in the alveolar space causes atelectasis, as the weight of fluid in one area can squeeze air out of, and collapse, areas below. Often this is the dorsal portion of lungs in a supine patient. Areas beneath fluid are termed dependant areas. The dependent areas may be different in each patient, and frequent CT scans (computed tomographs) are used to develop ventilation and positioning strategies as needed. Giattanoni et. al. write Early in the course of ALI/ARDS, CT is helpful in assessing the nature and extent of the patients' infiltrates and their response of mechanical ventilation. To limit radiation, the lung is usually imaged at two or three levels, repeating the same levels at different ventilator settings (e.g., end inspiration and at different PEEP levels). The use of different pressures helps to distinguish between areas of alveolar

Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE. collapse and consolidation, providing helpful information about mechanical ventilation parameters. (p. 1707) Figure 2 shows a series of CT scans with more and more alveoli recruitment in the ARDS patient. Finally, the numeric definition ARDS is taken from the PaO2/FIO2 ratio. ARDS is defined as a ratio of < 200, otherwise the classification is ALI, acute lung injury, when the ratio is <300. The etiology of ARDS is most commonly from aspiration of gastric

contents, or, water aspiration from near drowning. There are, however, a surprising variety of scenarios in which ARDS occurs; toxic smoke inhalation, pneumonia, and, lung radiation injury (Des Jardin 2011).

Study Ventilation and Titration. Ventilation is a complex process in ARDS treatment and will be discussed in detail. First, the ventilator settings for the average study patient are listed in Table 1, followed by the guide lines used for changing settings to meet goals in; oxygenation, plateau pressure, and hypercapnia. (Papazian et. al.2010) Cisatracurium Age 58 Tidal Volume ml/kg 6.55 Minute Ventilation 10.0 PEEP cm H2O 9.2 Plateau cm H2O 25.0 Respiratory-system compliance ml/cm H2O 31.5 FiO2 .79 PaO2 mmHg 80 PaCO2 mmHg 47 Table 1 (Derived from Table 2. Papazian et. al. 2010) Ventilation mode was volume assist-control in all cases. Mean Baseline Characteristics of Study Patient Placebo 58 6.48 10.1 9.2 24.4 31.9 .77 85 47

Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE.

Oxygenation targets are: PaO2 55-80mmHg or SPO2 88-95. To achieve Oxygenation targets the following FiO2 and PEEP combinations were allowed; FiO2 .3 .4 .5 .6 .7 .8 .9 1.0 PEEP cm H2O 5 5, 8 8, 10 10 10, 12, 14 14 14, 16, 18 18, 20, 22, 24

Secondary factors allowed to achieve oxygenation targets; 1. Inhaled nitric oxide (vasodilator.) 2. Almitrine dimesylate (respiratory stimulant.) 3. Prone positioning. 4. Any combination thereof. Pressure targets: if plateau pressure > 32 cmH2O for more than 10 minutes; 1. Increase sedation. 2. Reduce tidal volume to 4ml/kg. 3. Decrease PEEP by increments of 2 cmH2O and inject cisatracurium bolus of 20mg. Hypercapnia targets; if pH < 7.20; 1. Connect Y directly to tracheal tube. 2. Increase respiratory rate to 35/min. 3. Increase tidal volume to maximum 8ml/kg. Weaning strategy; Attempt on day 3 if FiO2 < .6. Goals: SpO2 >88%, Respiratory Rate 26-35. Procedure: decrease PEEP to 5cmH2O for 20 minutes. Pressure support during weaning; 20, 15, 10, 5 cm H2O. If wean fails at 20 cmH2O, return to volume assist-control. After 2 hours of successful pressure support ventilation at level of 5 cm H2O, disconnect patient from ventilator.

Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE. Summary.

Papazian et. als study administered 37.5 mg per hour of cisatracurium besylate for the first 48 hours of ventilation in ARDS patients. A blind placebo was given to a control group of patients. The result was a lower mortality rate, and lower rates of pneumothorax. The authors speculate the neuromuscular blockade (cisatracurium besylate) allows better initial titration of ventilator settings because of improved patient-ventilator synchrony. This makes intuitive sense to practitioners of respiratory care because hypercapnic PaCO2 levels associated with ARDS generate a strong respiratory drive in patients that are not chronic CO2 retainers. Sedation alone reduces the respiratory drive, however the drive is not eliminated. For this reason neuromuscular blocking seems to be the emerging standard for initial ARDS ventilation protocols. (Papazian et. al. 2010.)

Readers Critique.

Dr. Papazians work reports a study that takes into account a complex array of medical factors, and controls for a single variable, as much as possible. Developing evidence from a complex population such as ARDS patients takes a great deal of planning and analysis, and, the authors do a great job of organizing the contributions of seventeen medical professionals into a foundational piece respiratory knowledge. I suspect it will prove to be a useful lens through which to view my own clinical work, and for that I am very appreciative. In addition, Gattinonie and Pietro (1995) have done a substantial amount of work with ARDS patients, and I have selected an excerpt from their work below..

Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE.

We found that at plateau pressures of 21 to 46 cm H2O, most of the recruitment is accomplished however, what stays open then depends on the PEEP level. In this series of patients, only 15 and 20 cm H2O PEEP were sufficient to keep the acini open that were recruited at a higher plateau pressure. Thus, the CT scan confirms that after the recruitment maneuver causes complete opening, very high plateau pressure is not necessary. Rather, PEEP just has to be kept high enough to prevent end-expiratory collapse. (p. 1810). In figure 2, below, we can see some of the art to alveoli recruitment, outside of the focus of Papazians (2010) neuromuscular blocking study, but which can be woven into a complex understanding of ARDS ventilation by the respiratory practitioner.

Figure 2. (Gattinonie, L., Pietro, C., et. al. 2001)

Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE.

Diagram 1: Abnormal permeability will be in some areas, but not all areas of the lung. (adapted from Des Jardin 2011)

Running Head: ARDS VENTILATION WITH NEUROMUSCULAR BLOCKADE. References

Des Jardin, T., Burton, G.G.,(2011) Clinical Manifestations and Assessment of Respiratory Disease. St. Louis, MO: Mosby Elsevier. Gattinoni L, Caironi P, Pelosi P, Goodman LR. (2001) What has computed tomography taught us about the acute respiratory distress syndrome? Am J Respir Crit Care Med. 2001 Nov 1;164(9):1701-11 Gattinoni L, Pelosi P, Crotti S, Valenza F. (1995) Effects of positive end-expiratory pressure on regional distribution of tidal volume and recruitment in adult respiratory distress syndrome. Am J Respir Crit Care Med 1995; 151: 1807-1814 Med.Stanford.edu (2011) Disorders of Gas Exchange medresidents.stanford.edu/TeachingMaterials/Gas%20Exchange/Gas%20Exchange %20Handout.doc Accessed March 20, 2011. Papazian, L., Forel, J., Gacouin, A., Penot-Ragon, C., Perrin, G., Loundou, A., Jaber, S., Arnal, J., Perez, D., Seghboyan, J., Constantin, J., Courant, P., Lefrant, J., Guerin, C., Prat, G., Morange, S., Roch, A., (2010) Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome New England Journal of Medicine September 16, 2010 Vol.363 No. 12. Pilbeam, S., Cairo, J.M., (2006) Mechanical Ventilation: Physiological and Clinical Appliactions. St. Louis, MO: Mosby Elsevier.