Indian Journal of Anaesthesia

: 2008  |  Volume : 52  |  Issue : 2  |  Page : 148--158

Pneumonia in Intensive Care Unit

Vinay Joshi1, Gurjar Mohan2,  
1 Professor, Department of Anaesthesiology & Critical Care, S.N. Medical College, Jodhpur (Raj.), India
2 Assistant Professor, Department of Anaesthesiology & Critical Care, S.N. Medical College, Jodhpur (Raj.), India

Correspondence Address:
Vinay Joshi
Q.N.21, MG Hospital Campus, In front of Sanghi Petrol Pump, Station Road, Jodhpur (Raj) 342001


No large data based, or randomized controlled studies are available in reference to pneumonia in ICU especially in adult population, in India. Moreover the types of ICU infrastructure, sterilization& disinfection protocols, empirical antibiotics and antibiotics policy are standardized in the country. Hence this review article has mainly utilized available literature from developed countries. This review article briefly discusses the definition of various pneumonia, epidemiology, causative organism, patho­genesis, risk factors, diagnostic strategies and management modalities. By this article, authors hope that a certain guidelines or standardization of protocols in India will be formulated.

How to cite this article:
Joshi V, Mohan G. Pneumonia in Intensive Care Unit.Indian J Anaesth 2008;52:148-158

How to cite this URL:
Joshi V, Mohan G. Pneumonia in Intensive Care Unit. Indian J Anaesth [serial online] 2008 [cited 2021 Jan 18 ];52:148-158
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Full Text


In intensive care unit (ICU), a significant number of beds are occupied by the patients suffering from pneu­monia whether it is community or hospital acquired. The important factor is that pneumonia adds significantly to morbidity and mortality. The etiopathogenesis, pre-dis­posing factors, selection of the empirical antibiotics, an­tibiotic protocol in the ICU, diagnostic facility in the ICU, training of paramedical and treating physicians, caus­ative organisms, non adherence to aseptic precautions, lack of monitors and specific ventilators, type of ICU (open or close) are the important factors posing specific challenges in developing countries than in developed countries. Unfortunately, no large randomized, prospec­tive or retrospective literatures on this topic, especially for adults are available in context of India. The guide­lines provided by American Thoracic Society (ATS) [1],[2] are the major source for the content in this article.

Differentiations of different types of pneumonia are important as they differ in terms of predominance of caus­ative organism, selection of antibiotic, and course and prog­nosis of the disease. To be more precise, the pneumonia has been broadly categorized as community acquired pneu­monia (CAP) and hospital acquired pneumonia (HAP).


Pneumonia: infection of the lung that is most com­monly caused by bacteria but occasionally caused by viruses, fungi, parasites, and other infectious organisms.

Nosocomial pneumonia (NP) / Hospital acquired pneumonia (HAP): pneumonia that occurs 48 hours or more after admission, which was not incubating at the time of admission.

ICU-acquired pneumonia: pneumonia that arise more than 48 hours after ICU admission.

Ventilator-associated pneumonia (VAP): pneumonia that arises more than 48-72 hours after endotracheal intubation.

Early onset HAP& VAP: occurring within the first 4 days of hospitalization.

Late onset HAP& VAP: at 5 days or more of hospitalization.

Healthcare-associated pneumonia (HACAP): This includes any patient who was hospitalized in an acute care hospital for two or more days within 90 days of the infec­tion; resided in a nursing home or long-term care facility; received recent intravenous antibiotic therapy, chemo­therapy or wound care within the past 30 days of the cur­rent infection; or attended a hospital or hemodialysis clinic.


The incidence of pneumonia has been reported to be 5-10 cases per 1000 hospital admissions [3],[4],[5] , while in general ICU population incidence has ranged from 8­20% [6] . The risk of pneumonia increases by 6 to 20 folds in mechanically ventilated patients [3],[4],[5] . The risk of pneu­monia increases maximum during first five days. During first 5 days of ventilation, risk increases by 3%/day; during 5-10 days of ventilation it increases by 2%/day and af­ter 10 days of ventilatory support it increases by 1%each day [7] . In a recent PGI Chandigarh study, VAP was found to be 30.7% per 1,000 ventilator days.

 Causative organisms

Gram negative bacilli (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Acinetobacter species) are the main culprits for HAP (more than 60%). In patients with diabetes and trauma, Gram positive cocci such as Staphylococus aureus are emerging more common [8] . Anaerobic organism may be responsible following aspiration in non-intubated patient but is rare in VAP [9] .

In VAP, MRSA and K. pneumoniae are more com­mon in non ventilated rather than intubated patients [1] . S. pneumoniae and H. influenzae are frequently found in CAP and in early onset HAP in patients without other risk fac­tors, but are uncommon in late onset HAP. Legionella may be mainly responsible organism in immunocompromised patients. Fungal pathogens as Candida species and Aspergil­lus fumigatus may also occur in immunocompromised and organ transplanted patients. Influenza A is probably the most common viral cause of HAP.


In HAP, the major sources of infection are through healthcare devices, environment (air, water, equipment& fomites), and transfer of microorganism from health care provider to the patient [3],[4],[5],[10],[11],[12],[13] .

The major potential reservoirs for organisms in a human body are stomach and sinuses. From these po­tential sites, the bacteria get entry into the trachea via aspiration of oropharyngeal pathogens or via leakage of bacteria around endotracheal tube cuff [14],[15] . From tra­chea, the microbial pathogens migrate to lower respira­tory tract and here organisms are being colonized.

Against the invasion entry or migration of micro­bial pathogen, host defenses in the form of mechanical (ciliated epithelium and formation of mucus favoring expulsion of microorganism), in the form of humoral mechanism (formation of antibody and activation of com­pliment system) or in the form of cellular protection (through polymorphonuclear leucocyte, macrophages, lymphocytes and their cytokines) to expel the microor­ganism out or to kill them or to make them inactive [3],[16]. However if the defense mechanism is weak due to any factor or is insufficient to deal with the number of or­ganisms, infection at lower respiratory tract takes place.

 Risk factors

Certain risk factors have been identified which makes the patient more vulnerable for HAP:

 General: H/O smoking, advanced age, male sex

Disease: COPD, ARDS, burn, trauma, coma or impaired consciousness, multiple organ failure, longer sur­gical procedure, thoracic or upper abdominal operations, immunosuppression (including systemic corticosteroids,) hypoalbuminemia, high APACHE II score and etc.

Intervention: H2 blockers or antacids, mechanical ventilation more than three days, previous antibiotics, use of paralytic agents or continuous sedation, re-intubations, bronchoscopy, nasogastric tube, ICP monitoring etc.

 Modifiable risk factors

The risk of HAP in patients who are intubated and mechanical ventilated, is increased by 6 to 21 fold [10],[16]. Incidence of VAP can be reduced by maintaining endot­racheal cuff pressure at greater than 20 cm H2O and by continuous aspiration of subglottic secretions [15],[17],[18].

Possibly, incidence of HAP can be reduced by lim­iting the use of sedative& paralytic agents that depress cough and other host-protective mechanism and also by use of oral endotracheal& orogastric tubes, rather than nasotracheal& nasogastric tubes [17],[18],[19] . On the other side, incidence of VAP is not affected by frequent changing of ventilatory circuit and also by use of passive humidifi­ers or heat-moisture exchangers [20],[21] .

A significant threefold reduction occurred in the incidence of ICU-acquired HAP in patients treated in the semirecumbent position [22] . Postpyloric feeding as well as strategy of late administration (i.e. day 5 of intu­bation ) of enteral feeding is associated with significant reduction in ICU-acquired HAP [23],[24] .

In a randomized trial of post surgical patients, the use of oral antiseptic chlorhexidine was to be found with significantly reduction in rates of nosocomial infection [25] . Now a days routine prophylactic use of antibiotics as a selective decontamination of the digestive tract (SDD), to reduce HAP, is avoided due to high level of antibiotic resistance 1 . Unnecessary liberal use of allogenic blood products and old stored blood are found to be a risk fac­tor for increased incidence of HAP and in a prospective randomized trial comparing liberal and conservative "trig­gers" to transfusion in ICU patients not exhibiting active bleeding and without underlying cardiac disease demonstrated that awaiting a haemoglobin level of 7.0 g/dl as opposed to a level of 9.0 g/dl before initiating transfu­sion resulted in no adverse effects on outcome [26] .

A large, double blind, randomized trial comparing ranitidine with sucralfate demonstrated a trend towards lower rates of VAP with sucralfate, but clinically signifi­cant gastrointestinal bleeding was 4% higher in the sucralfate group [27] . Aggressive treatment of hypergly­cemia has both theoretical and clinical support, but may not lead to significant benefit in patient with VAP [1] .

A great emphasis should be to ensure effective infection control measure, which includes staff educa­tion, compliance with alcohol-based hand disinfection, and isolation to reduce cross-infection with MDR patho­gens, as these means reduce incidence of HAP by around half [10],[13],[28],[29] . Surveillance of ICU infections, to identify and quantify endemic and new MDR pathogens, and preparation of timely data for infection control and to guide appropriate, antimicrobial therapy in patients with suspected HAP or other nosocomial infections, are rec­ommended (Level II) [1] .


 Clinical and bacteriological strategy

The diagnosis of HAP is suspected if the patient has a radio-graphic infiltrate that is new or progressive, along with fever, purulent sputum, leukocytosis, and de­cline in oxygenation. The diagnostic criteria of a radio­graphic infiltrate and at least one clinical feature (fever, leukocytosis, or purulent tracheal secretions) have high sensitivity but low specificity (especially for VAP)[1] . Combinations of signs and symptoms may increase the specificity. When three clinical variables were used, the sensitivity declined, whereas the use of only one vari­able led to decline in specificity [1] .

All patients should have chest radiography, prefer­ably postero-anterior and lateral if not intubated. The radiography can help to define the severity of pneumo­nia and the presence of complications, such as effusions or cavitations [30] .

The clinical approach is overly sensitive, and it could be difficult to differentiate from other non-infectious conditions like congestive heart failure, atelectasis, pul­monary thromboembolism, pulmonary drug reactions, pulmonary hemorrhage, or ARDS [1] .

The clinical pulmonary infection score (CPIS) scor­ing system grades the severity of pneumonia and this include six features [31] . Each of these six features scores on a scale from 0 to 2, as follows: tracheal secretion: 0= rare, 1= abundant, 2= purulent; radiographic infiltrates: 0= absent, 1= patchy or diffuse 2= localized; fever (°C): 0=≥36.5 and ≤38.4, 1= >38.4 and ≥ 38.9, 2= > 38.9 or 11000, 2= 11000 and > 500 band forms; PaO2/FiO2: 0= >240 or acute respiratory dis­tress syndrome (ARDS), 2= ≤ 240 and no ARDS; mi­crobiology 0= negative, 2= positive.

The absence of a "gold standard" for HAP diagno­sis is a major problem, with which diagnostic results can be compared.

Although an etiologic diagnosis is made from a res­piratory tract culture, colonization of the trachea pre­cedes development of pneumonia in almost all cases of VAP, and thus a positive culture cannot always distin­guish a pathogen from a colonizing organism. However, a sterile culture from the lower respiratory tract of an intubated patient, in the absence of a recent change in antibiotic therapy, is strong evidence that pneumonia is not present, and an extra pulmonary site of infection should be considered (Level II) [1],[32].

Samples of lower respiratory tract secretions should be obtained from all patients with suspected HAP, and should be collected before antibiotic changes. Samples can include an endotracheal aspirate, bronchoalveolar la­vage (BAL) sample, or protected specimen brush (PSB) sample (Level II) [1] . A negative tracheal aspirate (absence of bacteria or inflammatory cells) in a patient without a recent (within 72 hours) change in antibiotics has a strong negative predictive value (94%) for VAP (Level II) [33] .

In a prospective study by Gibot and coworkers used a rapid immunoblot technique on BAL fluid in whom infec­tious pneumonia suspected, and found that levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) were the strongest independent predictor of pneumonia [34] .

Being multifocal nature of VAP, BAL and endot­racheal aspirates can provide more representative samples than the protected specimen brush (PSB), which samples only a single bronchial segment [1] .

Endotracheal aspirates can be cultured quantitatively, and with a threshold of 106cfu/ml or more, the sensitivity of this method for the presence of pneumonia has a mean of 76± 9% and specificity with a mean of 75±28% [35].

Bronchoscopic BAL studies have typically used a diagnostic threshold of 104cfu/ml. A review literature of 23 prospective studies of BAL in suspected VAP showed a sensitivity with a mean of 73± 18%, and a specificity with a mean of 82±19% [36].

Quantitative cultures of PSB samples have used a diagnostic threshold of 103cfu/ml or more. The sensitiv­ity and specificity for PSB have a mean 66±19%) and 90±15%, respectively [36],[37] . PSB appears to be more spe­cific than sensitive for the presence of pneumonia [36] .

If bronchoscopic sampling is not immediately available, non bronchoscopic sampling can reliably obtain lower respi­ratory tract secretions for quantitative cultures, which can be used to guide antibiotic therapy decisions (Level II) [38] .

Semi quantitative cultures of tracheal aspirates cannot be used as reliably as quantitative cultures to define the presence of pneumonia and the need for anti­biotic therapy (Level I). [39]


Approximately 10% of hospitalized patients with CAP require ICU admission. Direct admission to an ICU or high-level monitoring unit is recommended for patients either with any one of the major criteria or 3 of the mi­nor criteria for severe CAP (Level II) as listed in [Table 1] [2] . Summary of the recommended management of HAP as a algorithm is given in [Figure 1] [1] .

 Antibiotic therapy

Major points and recommendations for anti­biotic therapy : A major goal of therapy is eradication of the infecting organism, and so, antimicrobials are a mainstay of treatment. Delays in the initiation of appro­priate antibiotic therapy can increase the mortality of VAP and thus, therapy should not be postponed for the purpose of performing diagnostic studies in patients who are clinically unstable (level II) [40],[41].

Recommended empirical antibiotics for community­ acquired pneumonia who admitted to ICU are given in [Table 2] [2] . While, use the algorithm in [Figure 2] for HAP to select an initial empiric therapy based on the absence or presence of risk factors for MDR pathogens [Table 3]& [Table 4] (Level III) [1] .

These risk factors include prolonged duration of hospitalization (5 days or more), admission from a healthcare-related facility, and recent prolonged antibi­otic therapy (Level II) [42] .

A reliable tracheal aspirate Gram stain can be used to direct initial empiric antimicrobial therapy and may increase the diagnostic value of the CPIS (Level II) [43] . Therapy is modified on the basis of the clinical response on Days 2 and 3 [1] .

Choice of specific agents should be dictated by lo­cal microbiology, cost, availability, and formulary restric­tions (Level II) [44],[45] . Patients with healthcare-related pneumonia should be treated for potentially drug-resis­tant organisms, regardless of when during the hospital stay the pneumonia begins (Level II) [46] . Inappropriate therapy (failure of the etiologic pathogen to be sensitive to the administered antibiotic) is major risk factor for excess mortality and length of stay for patients with HAP, and antibiotic-resistant organisms are the pathogens most commonly associated with inappropriate therapy (Level II) [47] .

To achieve adequate therapy, it is necessary not only to use the correct antibiotic, but also the optimal dose and the correct route of administration (oral, intra­venous, or aerosol) to ensure that the antibiotic penetrates to the site of infection, and to use combination therapy if necessary. Most b lactam antibiotics achieve less than 50% of their serum concentration in the lung, whereas fluoroquinolones and linezolid equal or exceed their se­rum concentration in bronchial secretions [48] .

The mechanism of action of certain agents can also affect dosing regimens, efficacy, and toxicity. Some antimicrobials are bactericidal whereas others are bac­teriostatic. Bactericidal agents may act in a concentration dependent fashion (aminoglycosides and quinolones) or in a time dependent fashion (vancomycin and b lactam). Some antibiotics do have postantibiotic effect (PAE), as seen with aminoglycoside and quinolones while b lactam antibiotics lack this effect against gram nega­tive bacilli with the exception of carbapenem [49] .

There is a lot of debate over the use of antibiotics as monotherapy versus combination therapy. A meta­analysis has evaluated all prospective randomized trials of -lactam monotherapy compared with b lactam­aminoglycoside combination regimens in patients with sepsis, of whom at least around 15% patients had either HAP or VAP, showed clinical failure was more com­mon with combination therapy and there was no advan­tage in the therapy of P. aeruginosa infections, compared with monotherapy [50]. In addition, combination therapy did not prevent the emergence of resistance during therapy, but did lead to a significantly higher rate of neph­rotoxicity.

Combination therapy should be used if patients are likely to be infected with MDR pathogens (Level II) [42],[44], though no data documented the superiority of this ap­proach compared with monotherpay, except to enhance the likelihood of initially appropriate empiric therapy (Level I) [50] . If patients receive combination therapy with an aminoglycoside-containing regimen, the aminoglycoside can be stopped after 5-7 days in respond­ing patients (Level III) [51].

Monotherapy should be used and preferred over combination therapy whenever possible because combi­nation therapy is often expensive and exposes patients to unnecessary antibiotics, thereby increasing the risk of MDR pathogens and adverse outcomes [1] . Patients who develop nosocomial pneumonia with no risk factors for drug-resistant organisms are likely to respond to monotherapy with the antibiotics listed in [Table 3]. Monotherapy is also the standard when gram-positive HAP, including MRSA, is documented [1] . Monotherapy with ciprofloxacin has been successful in patients with mild HAP (defined as a CPIS of 6 or less) but is less effective in severe HAP [52] .

To use monotherapy in patients with severe VAP, the ATS committee believed that patients should initially receive combination therapy as described in [Table 4], but therapy could be changed to a single agent if cultures did not shown a resistant pathogen [44] .

Monotherapy with selected agents can be used for patients with severe HAP and VAP in the absence of resistant pathogens (Level I) [53],[54] . Patients in this risk group should initially receive combination therapy until the results of lower respiratory tract cultures are known and confirm that a single agent can be used (Level II).

If P. aeruginosa pneumonia is documented, com­bination therapy is recommended, mainly because of the high frequency of development of resistance on monotherapy [53] . Although combination therapy will not necessary prevent the development of resistance, com­bination therapy is more likely to avoid inappropriate and ineffective treatment of patients. (Level II) [44] .

In case of Acinetobacter species are to be present, the most active agents are the carbapenems, sulbactam, colistin, and polymyxin. There are no data documenting an improved outcome if these organisms are treated with a combination regimen. (Level II) [55] . If ESBL+ Enterbacteriaceae are present, then monotherapy with a third-generation cephalosporin should be avoided. The most active agents are the carbapenems (Level II) [56].

 Duration of therapy

If patients receive an initially appropriate antibi­otic regimen, efforts should be made to shorten the du­ration of therapy from the traditional 14 to 21 days to periods as short as 7 days, provided that the etiologic pathogen is not P. aeruginosa, and that the patient has a good clinical response with resolution of clinical features of infection (Level I) [57] . Patients with a low clinical sus­picion of VAP (CPIS of 6 or less) can have antibiotics safely discontinued after 3 days [52] .

Data support the promise that most patients with VAP, who receive appropriate antibiotic therapy, have a good clinical response within first 6 days. Prolonged therapy leads to colonization with antibiotic resistants.

 Aerosolized antibiotics

Aerosolized antibiotics have not been proven to have value in the therapy of VAP (Level I) [58] . But may be considered as adjunctive therapy with an inhaled amingolycoside or polymyxin for MDR gram negative pneumonia, especially in patients who are not improving with systemic therapy (Level III) [59] . More studies of this type of therapy are needed.

 Preference of particular antibiotic

Linezolide is an alternative to vancomycin for the treatment of MRSA VAP (Level II) and may also be preferred if patients have renal insufficiency or are re­ceiving other nephrotoxic agents, but more data are needed (Level III) [60],[61]

 Antibiotic rotation or restriction or holiday

Antibiotic restriction can limit epidemics of infec­tion with specific resistant pathogens. Heterogeneity of antibiotic prescriptions, including formal antibiotic cycling, may be able to reduce the incidence of antibiotic resis­tance. But, the long-term impact of this practice is un­known. (Level II) [62],[63] .

 Continuous versus intermittent infusion

Standard administration is by intermittent infusion; however, continuous infusion may be advantageous. Ef­ficacy of drug with bactericidal activity increases with the exposure time that could be well maintained above minimum inhibitory concentration (MIC) by the continu­ous infusion. However, sufficient evidence of its clinical efficacy is limited.

 Supportive therapy

Although supportive therapy like chest physio­therapy, postural drainage, humidification and aerosolisation with bronchodilators, mucolytic agents are crucial but with little documentation of efficacy in the management of pneumonia.


Patients with VAP had a longer duration of me­chanical ventilation and longer hospital stay. VAP has its own attributable mortality. The crude mortality rate has ranged from 25-70% in late onset HAP/VAP. The in­creased mortality rates were associated with aerobic gram negative bacteria (Pseudomonas aeruginosa, Acinetobacter species), associated with medical rather than surgical illness, inadequate& ineffective antibiotic therapy and also in patients who had acute respiratory distress syndrome [64],[65].


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