Ventilator-associated pneumonia | |
---|---|
Other names | Ventilator-acquired pneumonia |
Chest X-Ray of a person infected by pneumonia | |
Specialty | Critical Care Medicine Pulmonology Paediatric Critical Care Medicine Infectious Diseases |
Causes | Mechanical ventilation, Microaspiration past endotracheal tube cuff, prior use of broad-spectrum antimicrobials |
Ventilator-associated pneumonia (VAP) is a type of lung infection that occurs in people who are on mechanical ventilation breathing machines in hospitals. As such, VAP typically affects critically ill persons that are in an intensive care unit (ICU) and have been on a mechanical ventilator for at least 48 hours. [1] [2] VAP is a major source of increased illness and death. Persons with VAP have increased lengths of ICU hospitalization and have up to a 20–30% death rate. [3] The diagnosis of VAP varies among hospitals and providers but usually requires a new infiltrate on chest x-ray plus two or more other factors. These factors include temperatures of >38 °C or <36 °C, a white blood cell count of >12 × 109/ml, purulent secretions from the airways in the lung, and/or reduction in gas exchange. [2] [4]
A different less studied infection found in mechanically ventilated people is ventilator-associated tracheobronchitis (VAT). [5] As with VAP, tracheobronchial infection can colonise the trachea and travel to the bronchi. VAT may be a risk factor for VAP. [5]
People who are on mechanical ventilation are often sedated and are rarely able to communicate due to which many of the typical symptoms of pneumonia will either be absent or unable to be obtained. The most important signs are fever or low body temperature, new purulent sputum, and hypoxemia (decreasing amounts of oxygen in the blood). However, these symptoms may be similar for tracheobronchitis.
Risk factors for VAP include underlying heart or lung disease, neurologic disease, and trauma, as well as modifiable risk factors such as whether the head of the bed is flat (increased risk) or raised, whether the patient had an aspiration event before intubation, and prior antibiotic exposure. [3] As a result of intubation many of the body's defenses against infections are reduced or impaired; this can result in an ability for microorganisms to enter and cause infection. [6] [1] Patients who are in the ICU for head trauma or other severe neurologic illness, as well as patients who are in the ICU for blunt or penetrating trauma, are at especially high risk of developing VAP. [2] Further, patients hospitalized for blunt trauma are at a higher risk of developing VAP compared to patients with penetrating trauma. [2]
Ventilator-associated tracheobronchitis may be a risk factor for VAP, though not all cases of VAT progress to VAP. [7]
Recent studies have also linked the overall oral health of a patient to the potential development of VAP; suggesting that bacteria found in plaque can "migrate to the respiratory system." [8] [1]
The microbiologic flora responsible for VAP is different from that of the more common community-acquired pneumonia (CAP). In particular, viruses and fungi are uncommon causes in people who do not have underlying immune deficiencies. Though any microorganism that causes CAP can cause VAP, there are several bacteria which are particularly important causes of VAP because of their resistance to commonly used antibiotics. These bacteria are referred to as multidrug resistant (MDR).
It is thought by many, that VAP primarily occurs because the endotracheal or tracheostomy tube allows free passage of bacteria into the lower segments of the lung in a person who often has underlying lung or immune problems. Bacteria travel in small droplets both through the endotracheal tube and around the cuff. Often, bacteria colonize the endotracheal or tracheostomy tube and are embolized into the lungs with each breath. Bacteria may also be brought down into the lungs with procedures such as deep suctioning or bronchoscopy. Another possibility is that the bacteria already exist in the mucus lining the bronchial tree, and are just kept in check by the body's first line of defenses. Ciliary action of the cells lining the trachea drive the mucus superiorly, leading to a build-up of fluids around the inflated cuff where there is little to no airway clearance. The bacteria can then colonize easily without disturbance and then rise in numbers enough to become infective. The droplets that are driven into the airstream and into the lung fields are lofted by way of Bernoulli's principle. There is also a condition called oxidative damage that occurs when concentrations of pure oxygen come into prolonged contact with cells and this damages the cilia of the cells, thus inhibiting their action as part of the body's first line of defense.
Whether bacteria also travel from the sinuses or the stomach into the lungs is, as of 2005, controversial. However, spread to the lungs from the blood stream or the gut is uncommon.
Once inside the lungs, bacteria then take advantage of any deficiencies in the immune system (such as due to malnutrition or chemotherapy) and multiply. Patients with VAP demonstrate impaired function of key immune cells, including the neutrophil, both in the blood and in the alveolar space, [11] with this impairment being driven by pro-inflammatory molecules such as C5a. [12] These defects in immune function appear to be causally linked to the development of VAP, as they are seen before clinical infection develops. [13] A combination of bacterial damage and consequences of the immune response lead to disruption of gas exchange with resulting symptoms.
Diagnosis of ventilator-associated pneumonia is difficult and is not standardized. [14] The criteria used for diagnosis of VAP varies by institution, but tends to be a combination of several of the following radiographic, clinical sign, and laboratory evidence: [15]
As an example, some institutions may require one clinical symptoms such as shortness of breath, one clinical sign such as fever, plus evidence on chest xray and in tracheal cultures. [15]
There is no gold standard for getting cultures to identify the bacteria, virus, or fungus that is causing the pneumonia, and there are invasive and non-invasive strategies for obtaining the culture sample. [16] One non-invasive strategy collects cultures from the trachea of people with symptoms of VAP. Another is more invasive and advocates a bronchoscopy plus bronchoalveolar lavage (BAL) for people with symptoms of VAP. Both strategies also require a new or enlarging infiltrate on chest x-ray as well as clinical signs/symptoms such as fever and shortness of breath. There is no strong evidence to suggest that an invasive method to collect cultures is more effective than a non-invasive method. [16] In addition, a quantitative approach to assessing the culture (performing a bacterial count of the pathogen that is causing the pneumonia) does not appear to be superior to a qualitative approach (determining the presence of the pathogen). [16] In recent years there has been a focus on rapid diagnostics, allowing for detection of significant levels of pathogens before this becomes apparent on microbial cultures. Several approaches have been used, including using host biomarkers such as IL-1β and IL-8. [17] [18] Alternatively, molecular detection of bacteria has been undertaken, with reports that amplifying the pan-bacterial 16S gene can provide a measure of bacterial load. [19] A trial of biomarker-based exclusion of VAP (VAP-RAPID2) demonstrated test effectiveness but did not impact on clinical antibiotic prescribing decisions. [20] Studies of pathogen-focussed molecular diagnostics have shown more promise in improving antimicrobial prescribing, [21] [22] with formal findings from the INHALE randomised controlled trial awaited. Highly sensitive molecular diagnostics have the potential to increase antimicrobial use [23] as they detect dead or colonising bacteria, a combination of host-immune profiling and microbial detection may provide the optimal diagnostic technique. [24]
Blood cultures may reveal the microorganisms causing VAP, but are often not helpful as they are positive in only 25% of clinical VAP cases. [25] Even in cases with positive blood cultures, the bacteremia may be from a source other than the lung infection. [25]
Prevention of VAP involves limiting exposure to resistant bacteria, discontinuing mechanical ventilation as soon as possible, and a variety of strategies to limit infection while intubated. Resistant bacteria are spread in much the same ways as any communicable disease. Proper hand washing, sterile technique for invasive procedures, and isolation of individuals with known resistant organisms are all mandatory for effective infection control. A variety of aggressive weaning protocols to limit the amount of time a person spends intubated have been proposed. One important aspect is limiting the amount of sedation that a ventilated person receives.
Weak evidence suggests that raising the head of the bed to at least 30 degrees may help prevent VAP, however further research is required to understand the risks associated with this. [26] Antiseptic mouthwashes (in particular associated with toothbrushing) such as chlorhexidine may also reduce the risk of VAP, [27] although the evidence is mainly restricted to those who have undergone cardiac surgery. [28]
American and Canadian guidelines strongly recommend the use of subglottic secretion drainage (SSD). Special tracheal tubes with an incorporated suction lumen as the EVAC tracheal tube form Covidien / Mallinckrodt can be used for that reason. New cuff technology based on polyurethane material in combination with subglottic drainage (SealGuard Evac tracheal tube from Covidien / Mallinckrodt) showed significant delay in early and late onset of VAP. [29]
There is little evidence that the use of silver-coated endotracheal tubes reduces the incidence of VAP in the first ten days of ventilation. [30] There is tentative evidence that the use of probiotics may reduced the likelihood of getting VAP, however it is unclear if probiotics affect ICU or in-hospital death. [31]
Treatment of VAP should be matched to known causative bacteria. However, when VAP is first suspected, the bacteria causing infection is typically not known and broad-spectrum antibiotics are given (empiric therapy) until the particular bacterium and its sensitivities are determined. Empiric antibiotics should take into account both the risk factors a particular individual has for resistant bacteria as well as the local prevalence of resistant microorganisms. If a person has previously had episodes of pneumonia, information may be available about prior causative bacteria. The choice of initial therapy is therefore entirely dependent on knowledge of local flora and will vary from hospital to hospital. Treatment of VAP with a single antibiotic has been reported to result in similar outcomes as with a combination of more than one antibiotics, in terms of cure rates, duration of ICU stay, mortality and adverse effects. [32]
Risk factors for infection with an MDR strain include ventilation for more than five days, recent hospitalization (last 90 days), residence in a nursing home, treatment in a hemodialysis clinic, and prior antibiotic use (last 90 days).
Possible empirical therapy combinations include (but are not limited to):
Therapy is typically changed once the causative bacteria are known and continued until symptoms resolve (often 7 to 14 days). For patients with VAP not caused by nonfermenting Gram-negative bacilli (like Acinetobacter, Pseudomonas aeruginosa) the available evidence seems to support the use of short-course antimicrobial treatments (< or =10 days). [33]
People who do not have risk factors for MDR organisms may be treated differently depending on local knowledge of prevalent bacteria. Appropriate antibiotics may include ceftriaxone, ciprofloxacin, levofloxacin, or ampicillin/sulbactam.
As of 2005, there is ongoing research into inhaled antibiotics as an adjunct to conventional therapy. Tobramycin and polymyxin B are commonly used in certain centres but there is no strong clinical evidence to support their use.
VAP occurring early after intubation typically involves fewer resistant organisms and is thus associated with a more favorable outcome. Because respiratory failure requiring mechanical ventilation is itself associated with a high mortality, determination of the exact contribution of VAP to mortality has been difficult. As of 2006, estimates range from 33% to 50% death in patients who develop VAP. Mortality is more likely when VAP is associated with certain microorganisms (Pseudomonas, Acinetobacter), blood stream infections, and ineffective initial antibiotics. VAP is especially common in people who have acute respiratory distress syndrome (ARDS). [34] [35]
Between 8 and 28% of patients receiving mechanical ventilation are affected by VAP. [36] VAP can develop at any time during ventilation, but occurs most often in the first week of mechanical ventilation. [3] There is some evidence for gender differences in the course of VAP: men have been found to get VAP more often, but women are more likely to die after contracting VAP. [37] Recent reports indicate that patients with Coronavirus disease 2019 who require mechanical ventilation in an Intensive care unit are at increased risk of ventilator-associated pneumonia, compared to patients without COVID-19 ventilated in the same unit [38] and patients who had viral pneumonitis arising from viruses other than SARS-CoV-2. [39] Why this increased susceptibility should be present remains uncertain, as the noted reports [38] [39] adjusted for duration of ventilation, it is likely that the increased susceptibility relates impaired innate immunity in the lungs. [40] However several observational studies have identified the use of glucocorticoids as a factor associated with increased risk of VAP [41] [42] and other Hospital-acquired infections. [43]
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity of the condition is variable.
Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs.
Mechanical ventilation or assisted ventilation is the medical term for using a ventilator machine to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, with the main goal of helping the delivery of oxygen and removal of carbon dioxide. Mechanical ventilation is used for many reasons, including to protect the airway due to mechanical or neurologic cause, to ensure adequate oxygenation, or to remove excess carbon dioxide from the lungs. Various healthcare providers are involved with the use of mechanical ventilation and people who require ventilators are typically monitored in an intensive care unit.
Intensive care medicine, also called critical care medicine, is a medical specialty that deals with seriously or critically ill patients who have, are at risk of, or are recovering from conditions that may be life-threatening. It includes providing life support, invasive monitoring techniques, resuscitation, and end-of-life care. Doctors in this specialty are often called intensive care physicians, critical care physicians, or intensivists.
Extracorporeal membrane oxygenation (ECMO), is a form of extracorporeal life support, providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequate amount of oxygen, gas exchange or blood supply (perfusion) to sustain life. The technology for ECMO is largely derived from cardiopulmonary bypass, which provides shorter-term support with arrested native circulation. The device used is a membrane oxygenator, also known as an artificial lung.
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin coloration (cyanosis). For those who survive, a decreased quality of life is common.
Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.
Acinetobacter is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria. Acinetobacter species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification.
A hospital-acquired infection, also known as a nosocomial infection, is an infection that is acquired in a hospital or other healthcare facility. To emphasize both hospital and nonhospital settings, it is sometimes instead called a healthcare-associated infection. Such an infection can be acquired in a hospital, nursing home, rehabilitation facility, outpatient clinic, diagnostic laboratory or other clinical settings. A number of dynamic processes can bring contamination into operating rooms and other areas within nosocomial settings. Infection is spread to the susceptible patient in the clinical setting by various means. Healthcare staff also spread infection, in addition to contaminated equipment, bed linens, or air droplets. The infection can originate from the outside environment, another infected patient, staff that may be infected, or in some cases, the source of the infection cannot be determined. In some cases the microorganism originates from the patient's own skin microbiota, becoming opportunistic after surgery or other procedures that compromise the protective skin barrier. Though the patient may have contracted the infection from their own skin, the infection is still considered nosocomial since it develops in the health care setting. Nosocomial infection tends to lack evidence that it was present when the patient entered the healthcare setting, thus meaning it was acquired post-admission.
Artificial ventilation or respiration is when a machine assists in a metabolic process to exchange gases in the body by pulmonary ventilation, external respiration, and internal respiration. A machine called a ventilator provides the person air manually by moving air in and out of the lungs when an individual is unable to breathe on their own. The ventilator prevents the accumulation of carbon dioxide so that the lungs don't collapse due to the low pressure. The use of artificial ventilation can be traced back to the seventeenth century. There are three ways of exchanging gases in the body: manual methods, mechanical ventilation, and neurostimulation.
Aspiration pneumonia is a type of lung infection that is due to a relatively large amount of material from the stomach or mouth entering the lungs. Signs and symptoms often include fever and cough of relatively rapid onset. Complications may include lung abscess, acute respiratory distress syndrome, empyema, and parapneumonic effusion. Some include chemical induced inflammation of the lungs as a subtype, which occurs from acidic but non-infectious stomach contents entering the lungs.
Tracheobronchitis is inflammation of the trachea and bronchi. It is characterised by a cough, fever, and purulent sputum and is therefore suggestive of pneumonia. It is classified as a respiratory tract infection.
Community-acquired pneumonia (CAP) refers to pneumonia contracted by a person outside of the healthcare system. In contrast, hospital-acquired pneumonia (HAP) is seen in patients who have recently visited a hospital or who live in long-term care facilities. CAP is common, affecting people of all ages, and its symptoms occur as a result of oxygen-absorbing areas of the lung (alveoli) filling with fluid. This inhibits lung function, causing dyspnea, fever, chest pains and cough.
Bronchoalveolar lavage (BAL), also known as bronchoalveolar washing, is a diagnostic method of the lower respiratory system in which a bronchoscope is passed through the mouth or nose into an appropriate airway in the lungs, with a measured amount of fluid introduced and then collected for examination. This method is typically performed to diagnose pathogenic infections of the lower respiratory airways, though it also has been shown to have utility in diagnosing interstitial lung disease. Bronchoalveolar lavage can be a more sensitive method of detection than nasal swabs in respiratory molecular diagnostics, as has been the case with SARS-CoV-2 where bronchoalveolar lavage samples detect copies of viral RNA after negative nasal swab testing.
Respiratory tract infections (RTIs) are infectious diseases involving the lower or upper respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection or a lower respiratory tract infection. Lower respiratory infections, such as pneumonia, tend to be far more severe than upper respiratory infections, such as the common cold.
Hospital-acquired pneumonia (HAP) or nosocomial pneumonia refers to any pneumonia contracted by a patient in a hospital at least 48–72 hours after being admitted. It is thus distinguished from community-acquired pneumonia. It is usually caused by a bacterial infection, rather than a virus.
Pneumonia can be classified in several ways, most commonly by where it was acquired, but may also by the area of lung affected or by the causative organism. There is also a combined clinical classification, which combines factors such as age, risk factors for certain microorganisms, the presence of underlying lung disease or systemic disease and whether the person has recently been hospitalized.
Carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae (CPE) are gram-negative bacteria that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule. The resistance can vary from moderate to severe. Enterobacteriaceae are common commensals and infectious agents. Experts fear CRE as the new "superbug". The bacteria can kill up to half of patients who get bloodstream infections. Tom Frieden, former head of the Centers for Disease Control and Prevention has referred to CRE as "nightmare bacteria". Examples of enzymes found in certain types of CRE are KPC and NDM. KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM have also been reported in Pseudomonas.
Prone ventilation, sometimes called prone positioning or proning, is a method of mechanical ventilation with the patient lying face-down (prone). It improves oxygenation in most patients with acute respiratory distress syndrome (ARDS) and reduces mortality. The earliest trial investigating the benefits of prone ventilation occurred in 1976. Since that time, many meta-analyses and one randomized control trial, the PROSEVA trial, have shown an increase in patients' survival with the more severe versions of ARDS. There are many proposed mechanisms, but they are not fully delineated. The proposed utility of prone ventilation is that this position will improve lung mechanics, improve oxygenation, and increase survival. Although improved oxygenation has been shown in multiple studies, this position change's survival benefit is not as clear. Similar to the slow adoption of low tidal volume ventilation utilized in ARDS, many believe that the investigation into the benefits of prone ventilation will likely be ongoing in the future.
Proning or prone positioning is the placement of patients into a prone position so that they are lying on their front. This is used in the treatment of patients in intensive care with acute respiratory distress syndrome (ARDS). It has been especially tried and studied for patients on ventilators but, during the COVID-19 pandemic, it is being used for patients with oxygen masks and CPAP as an alternative to ventilation.