We are each constructed of about 100 trillion cells forming tissues, organs, and nerve tracts; establishing highly organized systems directed by our DNA codes, chemical reactions and electrical impulses. We are tough enough to house quadrillions of bacteria in the 28 feet or so of intestinal tubing, survive being tackled at full speed just shy of the end zone and run 26-mile marathons. Each breath we take expands 300 million alveolar balloons, an average of 20,000 times a day. Our biological systems are integrated to make energy production, physical movement, air intake, oxygen delivery and even cognitive thought possible; things we take for granted until something goes wrong. The incredible integration of our physical, chemical and electrical systems also makes us vulnerable. We can be severely incapacitated as systems impact systems due to a missing enzyme, insufficient oxygen, too little surfactant, a suppressed immune system, the aspiration of chemicals, particulates or pathogens, etc. One adverse event can topple a chain of dominoes impacting many bodily functions. It is imperative that when we observe, assess, and treat our patients, we do so by looking at overall consequences. For the patient on a ventilator, we must look at the whole landscape of potential ventilator-associated adverse events, understand the primary triggers that initiate cascading consequences and implement best practices to prevent their occurrence.
The three most prominent “trigger categories” for initiating these adverse events are: 1) the aspiration of chemicals and non-microbial particulates; 2) the aspiration of pathogens; and 3) mechanical injury to the pulmonary tissues. By implementing preventative bundles addressing these three major triggers, the majority of adverse events associated with being on a ventilator can be avoided. The chart in Figure 1, outlines potential cascading events from the three major triggers. If a trigger event occurs, not all of the adverse consequences listed under each category would present as underlying morbidities, the nature of the trigger and other variables would determine the adverse event progression. By the same token, the chart does not include every complication possible. It does, however provide a framework by which preventative actions can be logically defined and implemented to provide a holistic, patient-centered approach for optimal outcomes.
Chemical and Particulate Aspiration
Focusing on the intubated patient, aspiration pneumonitis is defined as lung injury that primarily occurs after inhalation of gastric contents.1 Mendelson demonstrated that aspiration of acidic gastric contents into the lungs caused severe injury to the pulmonary tissues (pneumonitis) equal to the severity as that caused by the same volume of 0.1N hydrochloric acid.2 After the initial injury, chemotactic signals are sent out from the damaged parenchymal cells summoning neutrophils. These immune cells release destructive oxygen radicals damaging both the alveoli and the interstitial tissues. Pro-inflammatory enzymes are released and complement components cascade into destructive escalation of acute lung injury.
If food particles or other particulates are also present in the aspirate, the damage is strongly amplified as the immune system, in its efforts to rid the lungs of the unwanted invaders, up-scales its inflammatory activities significantly increasing tissue damage.3,4 The injured lungs are now very vulnerable to infection, whether from aspiration of a few microorganisms or the arrival of pathogens in the bloodstream from a remote location, potentially resulting in secondary pneumonia, a complication that occurs in up to 25% of pneumonitis patients.5
During the destructive, inflammatory activities, alveolar capillaries become more permeable allowing white cells and protein-loaded blood serum into the injured area. Unfortunately, the proteins degrade pulmonary surfactants causing the still-functioning alveoli in the region to become sticky. The snapping open as the alveoli overcome the lack of lubricity escalates the regional inflammation as tissues are torn, and the alveoli collapse. Expanding areas of atelectasis occur resulting in regional collapse. The serum proteins and damaged tissues set up a concentration gradient drawing in more fluids which flood the injured tissues and fill surrounding alveoli. Gas exchange is no longer occurring in the affected region. Acute respiratory distress is initiated. The influx of fluids increases the weight and pressure on the affected area. While the alveolar membranes are being actively damaged, they become unable to contain the incoming air from the ventilator. Air escapes outside the injured alveoli, coalesces with other air “bubbles,” and potentially sets the stage for pneumothorax.
With the increased permeability of the surrounding capillaries, the proinflammatory mediators enter the circulation escalating the pulmonary inflammatory response into a systemic condition known as Systemic Inflammatory Response Syndrome (SIRS), precursor to non-infectious sepsis. If unable to stop the cascade, the patient may spiral to further critical sequelea, including severe sepsis, multi-organ dysfunction syndrome (MODS), septic shock, multi organ failure (MOF) and death.
Within 24-48 hours of admission, all critically ill patients will acquire respiratory pathogens in their oropharynx.6-9 These pathogens invade and multiply in the biofilm of the teeth (dental plaque) and surrounding soft tissues.10,11 A mature biofilm contains >108 (100 million) bacteria per cubic millimeter.12 The higher the plaque scores, the greater the risk of pneumonia in the intubated patient.13 If early and frequent appropriate oral hygiene is not conducted during the 72 hours since the patient’s teeth were last brushed, hard calcium-phosphate crystalline structures form protecting the biofilm. These structures, termed calculus, can only be removed by the hygienists pick. The Centers for Disease Control and Prevention (CDC) states that in 76% of ventilator-associated pneumonia (VAP), bacteria colonizing the mouth before pneumonia is diagnosed are the same as those causing the pneumonia.14
Metabolites are released from the plaque bacteria inflaming the surrounding tissues. Capillaries in the gums dilate, becoming increasingly permeable, releasing fluid cytokines into the tissues causing the gums to become increasingly red and swollen. These proinflammatory agents enter the systemic circulation and increase the risk of cardiac infarction of the vulnerable.15 Bacteria released from the mature biofilm continue to expand the plaque. Some of the bacteria enter the permeable capillaries and are transported through the systemic circulation, potentially initiating infections in remote locations. They may cling to damaged heart valves, pace maker leads or any vulnerable remote location.
Bacteria also multiply within the sinus tracts if drainage is blocked by a nasogastric tube causing sinusitis, a pathogen reservoir.16 The tube also provides a great surface for biofilm construction, advancing the bio-structure and inhabitants into the oropharynx.17 The nasogastric tube damages the nasal and oropharyngeal mucosal tissues by friction-abrasion, increases gastric reflux, and bacterial colonization of the esophagus and stomach.18
Eventually, with the endotracheal tube in place, its cuff inflated and the epiglottis propped open, secretions drain from the oropharyngeal cavity into the space above the cuff, becoming the subglottic pool. Bacteria from the oropharynx, dental plaque, periodontal tissues and tongue drain into the pool where they multiply. If some of the pathogen-rich pool leaks past the cuff and is aspirated into the lungs of the vulnerable mechanically ventilated patient, the first stages of colonization and infection commence. If the local immune response is unable to eliminate the threat, the respiratory pathogens and opportunistic bacteria multiply. Inflammation increases as recruited neutrophils, complement proteins and cytokines damage alveolar tissues in expanding efforts to prevent the advancing infection. Heightened inflammatory response and falling oxygen levels can lead to acute respiratory distress syndrome (ARDS) and chronic pulmonary fibrosis.
If the initial microbial concentration was high, or encased in biofilm matrix, a bolus inoculation in the lung can form the center of a pulmonary abscess, even more resistant to immune cell attack and antibiotic treatments than the biofilm alone. With or without an abscess, inflammatory damage to local tissues can expand to regional involvement. Inflammatory proteins degrade the lubricating surfactants; fluids enter the area due to the osmotic pull and damaged tissues. Atelectasis occurs, oxygen saturation begins to fall. Incoming air can leak into the pleural cavity potentially leading to pneumothorax.
The pro-inflammatory agents enter the damaged capillaries initiating SIRS, similar to that which occurs in aspiration pneumonitis, except that bacteria and endotoxin also enter the circulation potentially leading to infectious sepsis, remote infections, MOD, septic shock, MOF and death.
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Starting with insertion, the endotracheal tube becomes contaminated as it contacts the oral cavity. Depending on the amount of contamination, this can lead to early seeding of the lungs with opportunistic bacteria. Difficult insertions with multiple attempts increase the risk of heavy contamination and tissue damage. If vocal cords or tracheal tissues are injured, the damaged tissue provides a niche within which bacteria from the oropharynx can invade and multiply providing another reservoir to seed the subglottic pool. Cuff over-inflation can cause ischemic injury to the contacted mucosal tissues. Bacteria can enter the damaged tissue, multiply and potentially migrate past the bulging cuff to enter the trachea and be aspirated.
Ventilator induced lung injury (VILI) is largely due to injury caused by alveolar over-distension (barotrauma) caused primarily by high tidal volumes and repeated atelectasis. Interstitial emphysema, pneumothorax, pneumomediastinum, pneumopericardium, pneumoperitoneum, and embolism may occur (Parker). Later, pulmonary fibrosis can be a chronic condition. The alveolar damage and up-regulation of the inflammatory response referred to as biotrauma, can lead to the sequence of events identified earlier as the pro-inflammatory agents enter the systemic circulation through damaged alveolar capillaries. If the patient continues to spiral, non-infectious sepsis ensues followed by SIRS, MODS, septic shock, and death. ARDS is both an independent risk factor for further injury and progression to the most severe sequelea, as well as one of the potential complications of pulmonary trauma.19
All of the pathways and complications described have one thing in common; the patient is intubated on mechanical ventilation. Underlying morbidities can exacerbate the potential for complications, but are not necessary. Looking at each individual injurious step and trying to address it is overwhelming. Preventing the three major pathways — aspiration pneumonia, aspiration pneumonitis and mechanical injury — before they occur is far less daunting, less expensive and more protective of the patient. Certainly every reader has seen these recommendations many times before, but realizing that the effort put forth can prevent so many spiraling consequences, makes attention to compliance details “worth the effort.” The list below reflects guidelines and recommendations from several agencies:
Prevent Chemical, Particulate, and Pathogen Aspiration
- Elevate head of bed 30ø-45ø (closer to 45ø the better (unless contraindicated); 28ø is not sufficient to reduce reflux or aspiration) all the time, but particularly when feeding or performing oral care.20
- Do not overfeed patient.
- Do not feed within 4 hours of:
- Consider reducing gastric acidity to minimize pulmonary injury should aspiration occur and to reduce stress ulcers. (practice can be controversial as resulting pH is no longer low enough to kill bacteria entering stomach, allowing bacteria to multiply)
- Comprehensive oral hygiene program
- Perform oral assessment as soon as possible and performed daily per a written procedure.
- Brush teeth and gums at least 2X daily using soft brush: breaks down biofilm/dental plaque, and stimulates the tissues.
- Moisturize mucosa & lips every 2-4hrs to prevent chapping as the cracks created provide niches for bacterial colonization.
- Use antiseptic mouth rinse: 0.12% chlorhexidine gluconate (CHG) recommended by Institute of Healthcare Improvement (IHI) for all patients on a respirator; alternatives include hydrogen peroxide, cetylpyridinium citrate (CPC), povidone iodine.
- Use oral suction while performing oral care to prevent drainage into subglottic pool.
- Avoid use of nasogastric tube if at all possible.
- Use appropriate and timely hand hygiene.
- Disinfect environment and equipment frequently. It is important to note that most respiratory pathogens remain infective on dry surfaces for days to weeks.21
- Endotracheal tube (ETT) and cuff maintenance:
- Use a micro-thin polyurethane cuffs are they are tissue compatible, conform well to the mucosal surface and maintain a seal without excessive pressure. Because micro-thin polyurethane adheres to itself, the channel formation and associated subglottic pool leaks that occur with vinyl, and silicone cuffs is averted.
- Secure the ETT well to the maxilla giving increased stability to prevent accidental seal disruption. Securing to maxilla also provides better access for oral care.
- Routinely check cuff pressure to make certain optimal level is maintained. Note: tremendous variation in cuff pressure occurs during airborne patient transport. The higher the elevation, the more the cuff expands (sometimes injuriously so).
- Use a subglottic secretion suctioning device incorporated into endotracheal tube as it provides more efficient, effective subglottic pool removal and reduces risk of injury compared to using a hand held suction catheter.
- Post signs for visitors with hand hygiene instructions and explanations as to why the patient cannot be moved, pillows fluffed or tubing manipulated.
- Closed suctioning rather than open suction maintains PEEP to reduce atelectasis and the risk of progression to surfactant degradation and up-regulated inflammation during repeated recruitment. Closed suction reduces environmental contamination that could be transported to other vulnerable patients.
- During tracheal suction, draw catheter up the inside of the ETT smoothly. Do not flip catheter around as bacterial laden biofilm fragments can be broken off, to be aspirated as a bolus inoculation.
- Implement daily sedation vacation to determine when ETT can be removed. Suction subglottic pool before initiating increased consciousness as patient may inadvertently dislodge cuff seal.
Avoid Mechanical Injury
- Use aids as recommended by your institution (e.g., conventional laryngoscope, flexible fiberoptic bronchoscope, video laryngoscope) to ensure proper insertion and placement while avoiding injury to vocal cords and surrounding tissues.
- Use an ETT with a narrow profile, transparent cuff to better visualize positioning and can reduce injury.
- Use a low volume, low pressure cuff made of micro-thin polyurethane to reduce risk of tissue injury and improve seal.
- There is no absolute threshold for the plateau airway pressure as individual pulmonary conditions vary significantly. However, plateau airway pressures equal to or below 30cm H20, are recommended. Levels greater than 35cm H20 increase the risk of barotrauma.
- Maintain a low PEEP to mitigate end-expiratory alveolar collapse and thus reduce the inflammatory response occurring with atelectic cycling and alveolar damage. Consistent PEEP requires closed suction system. For critical patients intolerant to even minimal PEEP fluctuations, a sealed port closed suction device is recommended.
It is in the patient’s and facility’s best interest to take a holistic approach to the prevention of ventilator-associated adverse events. Helping staff to understand the pathological sequences they can avoid by addressing the three major categories will make compliance easier, because it makes sense rather than, “I have to check the box.”
- Marik PE. Aspiration Pneumonitis and Aspiration Pneumonia. N Eng J Med 2001;344(9):665-661.
- Mendelson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. AM J Obstet Gynecol 1946;52:191-205.
- Knight PR, Rutter T, Tait AR, Coleman E, Johnson K. Pathogenesis of gastric particulate lung injury: a comparison and interaction with acid pneumonitis. Anesth Analg 1993;77:754-760.
- Teabeaut JR. Aspiration of gastric contents: an experimental study. Am J Pathol 1952;28:51-67.
- O’Connor S. Aspiration pneumonia and pneumonitis. Aust Prescr 2003;26:14-17.
- Garcia R. A review of the possible role of oral and dental colonization on the occurrence of healthcare-associated pneumonia: underappreciated risk and a call for interventions. Am J Infect Control. 2005;33:527-541.
- Garcia R, Jendresky L, Colbert L. Reducing ventilator-associated pneumonia through advanced oral-dental care: A 48-month study. Am J Crit Care. 2009;18:523-532.
- Safdar N, Crnich CJ, Maki DG. The pathogenesis of ventilator-associated pneumonia: Its relevance to developing effective strategies for prevention. Resp Care. 2005;50:725-739.
- Abele-Horn M, Dauber A, Bauernfeind A, et al. Decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (SOD). Intensive Care Med. 1997;23(2):187-195.
- Scannapieco FA, Stewart EM, Mylotte JM. Colonization of dental plaque by repiratory pathogens in medical intensive care patients. Crit Care Med. 1992;20(6):740-745.
- Fourrier F, Duvivier B, Boutigny H, Roussel-Delvallez M, Chopin C. Colonization of dental plaque: a source of nosocomial infections in intensive care unit patients. Crit Care Med. 1998;26:301-308.
- Gibbons RJ: Bacterial adhesion to oral tissues: A model for infectious diseases. J Dent Res 1989;68:750-760.
- Munro CL, Grap MJ, Elswick RK, Jr, et al. Oral health status and development of ventilator-associated pneumonia: a descriptive study. Am J Crit Care. 2006;15:453-460.
- Centers for Disease Control and Prevention. Guideline for the prevention of nosocomial pneumonitis. MMWR 1997;46(RR-1).
- Genco RJ. Periodontal disease and risk for myocardial infarction and cardiovascular disease. CVR&R. 1998:34-40.
- Talmor M, Li P, Barie PS. Acute paranasal sinusitis in critically ill patients: Guidelines for prevention, diagnosis, and treatment. Clin Infect Dis 1997;25:1441-1446.
- Leibovitz A, Baumoehl Y, Steinberg D. Biodynamics of biofilm formation on nasogastric tubes of the elderly. Isr Med Assoc J. 2005;7(7):483-430.
- Marrie TJ, Sung JY, Costerton JW. Bacterial biofilm formation on nasogastric tubes. J Gastroenterol Hepatol. 1990;5(5):503-506.
- Parker JC, Hernandez LA, Peevy KJ. “Mechanisms of ventilator-induced lung injury”. Crit Care Med 1993;21(1):131-143.
- van Nieuwenhoven CA, Vandenbroucke-Grauls C, van Tiel FH, et al. Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study. Crit Care Med. 2006;34(2):396-402.
- Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infectious Diseases 2006;6:3130.