Chapter 2 Materials and Methods
2.3 Statistical Analysis
The data were compiled and analyzed by using a commercial statistical software
(SPSS for Windows, version 10.0, Chicago, IL, USA). All continuous data are
expressed as means ± standard deviation (SD) and compared using a two-tailed
Student t test. Categoricalvariables are reported as a percentage and compared using
chi-square or Fisher exact test,when appropriate. A multivariate stepwise logistic
regression analysis is used to identify independently significant factors in predicting
in-hospital mortality. A p<0.05 was considered statistically significant.
Results
3.1 Comorbidity and Clinical Symptoms
Among the enrolled 72 patients admitted to ICU, concomitant underlying
diseases were frequently found at the time of admission and the most common was
diabetes mellitus (n=37, 51%) followed by alcoholism (n=17, 24%), biliary stone
(n=11, 15%), uremia (n=7, 10%), malignancy (n=5, 7%) and liver cirrhosis (n=2, 3%).
The most common clinical features were fever with chills (n=46, 64%) and abdominal
pain (n=12, 17%), besides, the other presenting symptoms included general malaise
(n=5, 7%), nausea or vomiting (n=6, 8%), altered mental status (n= 4, 6%), jaundice
(n=2, 3%) and diarrhea (n=1, 1 %) [Table 1]. The duration of symptom before
admission ranged from 1 to 10 days with a mean of 4.3±5.0 days.
Further comparing the general characteristics between the survivors (n=52) and
nonsurvivors (n=20), we found that there were no differences in gender, age, body
mass index, duration of symptoms before admission, presenting symptoms and
underlying diseases. Only Glasgow Coma Scale (GCS) and APACH II score of the
first day ICU admission had statistical significance between the two groups (p<0.05),
as shown in Table 1 in detail.
3.2 Abscess Size, Bacteriology and Treatment
The size of abscess measured by computed tomography of abdomen ranged from
1 to 12 cm in diameter, with a mean of 5.2±3 cm. The majority of abscess was solitary,
which was found in 49 of 72 patients (68.1%). Further analysis of bacteriology,
aspirated pus cultures were obtained in 61 patients with a positive culture rate of
85.2% (52/61), and positive rate of blood culture was 70.8 % (51/72). Moreover,
polymicrobial infections were found in 13.9 % of the positive cultures. Klebsiella
pneumoniae (74 %) was the most common organism isolated either from blood
culture or pus culture, followed by Escherichia coli (18 %), Streptococcus spp. (7 %),
and Enterococcus spp. (5 %). In addition, only four patients were infected by
anaerobes, including Bacteroide fragilis (n=2) and Fusobacterium (n=2).
In our series, therapeutic options for PLA included percutaneous drainage
combined with antibiotics, surgery, and antibiotics only. Seven patients were treated
with antibiotics alone and sixty-one (84%) patients initially received antibiotics
treatment combined with percutaneous drainage, however, two patients subsequently
failed and therefore underwent surgical intervention. Laparotomy was performed in 6
patients, including peritonitis caused by ruptured abscess (n=3), failure of
percutaneous drainage (n=2), and abscess with hepatolithiasis (n=1). Further analysis
of the above variables, we found that there was no statistical significance between the
two groups. Table 2 showed the bacteriology and treatment in detail.
3.3 Complication, Mortality and Prognostic Factors
Among the enrolled 72 patients with PLA admitted to ICU, twenty patients died,
yielding an ICU mortality rate of 28%, and an overall mortality rate of PLA about
4.6%. Almost all deaths were PLA related, except one patient died of acute
myocardial infarction while treating abscess. Seventeen (85%) patients were died of
septic shock and the remaining two (10%) patients were died of ARDS. Laboratory
data of survivors and nonsurvivors on the first day of ICU admission both
demonstrated leukocytosis, anemia, abnormal liver and renal function tests, markedly
elevated C-reactive protein, hypoalbuminemia, and prolonged prothrombin time (PT).
However, only serum creatinine concentration (1.9±2 vs. 2.9±2, p<0.05) and PT (16±5
vs. 21±5, p<0.05) were statistically significant between the two groups [Table 3].
The most common clinical course related complications of ICU admission were
septic shock (n=40, 56 %), followed by acute renal failure (n=33, 46 %), DIC (n=26,
36 %) and acute respiratory failure (n=23, 21 %). Particularly, eight (11 %) patients
developed metastatic infections, including endophthalmitis (n=4), meningitis (n=2),
pulmonary septic emboli (n=1), and septic arthritis (n=1). The length of ICU stay
ranged from 1 to 31 days (mean = 10±10 days) and total hospital stay ranged from 1
to 125 days (mean = 31±38 days). Further comparing these variables, as shown in
Table 4, the existence of septic shock, acute renal failure, or respiratory failure were
significantly lower in survivors than in nonsurvivors (p<0.05). Significant factors
were also analyzed again by multiple logistic regression analysis [Table 5], and the
results revealed that the presence of acute respiratory failure on the first ICU
admission day and APACHE II score > 16 were the best independent predictors of
prognosis. Especially, in patients with PLA requiring critical care, occurrence of acute
renal failure in combination with acute respiratory failure reached mortality rate of 81
%. Occurrence of acute respiratory failure with APACHE II score > 16 reached
mortality rate of 92 %.
Discussion
To our knowledge, this is the first retrospective study focusing on outcomes and
predictors of mortality in patients with PLA requiring intensive care. Our study
showed that 17 % of all PLA (72/436) were critically ill patients requiring intensive
care and that yielded a mortality rate of 28 %. Moreover, the most common
underlying disease was diabetes mellitus, and the most common isolated
microorganism was Klebsiella pneumoniae. The occurrences of higher APACHE II
score (>16) and presence of acute respiratory failure on the first day of ICU admission
significantly increased the likelihood of mortality.
Although the general condition of enrolled patients was relatively critical in this
series, the clinical features, age and gender distribution of PLA patients were similar
to that of previous reports [12, 23-24]. The major presenting symptoms were fever,
chills and abdominal pain, however, a few patients presented with only altered mental
status, dizziness or general malaise. As reported by previous literature [12, 25-26],
diabetes mellitus was also the most common underlying disease in our series,
followed by alcoholism, biliary tract disease and malignancy. Surprisingly, rare study
reported that alcoholism was one of the most common concomitant medical problems
in PLA [27].
Consistent with previous investigations [12-13, 25-27], Klebsiella pneumoniae
was the most commonly isolated microorganism (74%) in this study. The unique
characteristic of Klebsiella pneumoniae liver abscess was its potential for septic
metastatic infection, which may present as endophthalmitis, pulmonary septic emboli,
meningitis, or septic arthritis [21, 28]. In our series, two patients presented as fever,
headache, and altered mental status without gastrointestinal symptoms were initially
diagnosed as bacterial meningitis. However, blood cultures yielded Klebsiella
pneumoniae three days later after admission, and then liver abscess was found by
bedside ultrasound. Therefore, it is crucial to employ a diagnostic work-up for
metastatic complications in PLA, especially in patients concomitant with diabetes
mellitus [27] or bacterial culture yielding Klebsiella pneumonia. Interestingly,
Klebsiella pneumonia liver abscess is a prominent pathogen in Taiwan and many
studies had been reported its special characteristics. Wang JH et al. found that
Klebsiella pneumonia related PLA had higher incidences of diabetes or glucose
intolerance (75% vs. 4.5%) and metastatic infections (11.9% vs. 0) and lower rates of
intra-abdominal abnormalities (0.6% vs. 95.5%), mortality (11.3% vs. 41%), and
relapse (4.4% vs. 41%) compared with non- Klebsiella pneumonia group [29]. To
investigate the frequency of hypermucoviscosity in bacteraemic isolates of Klebsiella
pneumonia, and to determine the significance of any association between HV and
various clinical manifestations, Lee HC et al. found that the hypermucoviscosity
phenotype of Klebsiella pneumonia bacteraemic isolates was associated with the
development of a distinctive invasive syndrome [30]. To identify risk factors for
spontaneous rupture of liver abscess caused by Klebsiella pneumoniae, one study
reported that patients with spontaneous rupture of liver abscess were found to have
significantly higher proportions of diabetic mellitus (100% versus 62.1%, P = 0.003),
larger abscess size (mean of maximal diameter 7.8 versus 6.1 cm, P = 0.043), gas
formation in abscess (87.5% versus 23.5%, P < 0.001), and left hepatic lobe
involvement (50.0% versus 16.5%, P = 0.018). K. pneumoniae serotypes K1 and K2
were the predominant microorganisms isolated in both patients with non-rupture of
liver abscess and spontaneous rupture of liver abscess. Pulsed-field gel
electrophoresis-generated fingerprinting of Klebsiella pneumoniae isolates from
patients with spontaneous rupture of liver abscess revealed that these pathogens were
non-genetically related [31].
Reviewing the literature, the most common risk factors for PLA were malignancy,
immunosuppression, diabetes, and previous biliary surgery or interventional
endoscopy. Particularly in East Asia, diabetes mellitus is an important risk factor, but
formal evidence is limited. Therefore Thomsen RW et al. conducted a case-control
study with participants drawn from the entire population of Denmark, which showed
that Diabetes is a strong, potentially modifiable risk factor for PLA. PLA is associated
with a similarly poor prognosis for patients with diabetes and for other patients [32].
In another study, Kaplan GG et al. reported that liver transplantation patients,
diabetics, and patients with a history of malignancy were associated with significantly
higher risk for developing a PLA [33]. Metastatic infection was also a special
demonstration of PLA and most common metastatic infection organs included brain,
lung, spleen, and eye. To identify the risk factors for developing extra-hepatic
metastases from PLA, Chen SC et al. suggest that diabetes mellitus and alcoholism
are significant risk factors for developing metastatic infections from pyogenic liver
abscesses [27]. In the aspect of PLA associated septic endophthalmitis, one study
concluded that physicians should be alert to the development of endogenous
Klebsiella pneumoniae endophthalmitis when patients with diabetes along with
Klebsiella pneumoniae –induced PLA complain of ocular symptoms. In the majority
of patients with endogenous Klebsiella pneumoniae endophthalmitis associated with
PLA, visual outcome is generally poor despite aggressive antibiotic therapy. Early
diagnosis and prompt intervention with intravitreal antibiotics within 48 hours may
salvage useful vision in some patients with endogenous Klebsiella pneumoniae
endophthalmitis [34].
Recently the introduction and refinement of percutaneous drainage techniques
have dramatically improved the treatment success rate [10, 12], however, it seemed
not to influence the outcome of critically ill patients with PLA in our study. Probably
most patients in our series were in severe sepsis, so that the treatment should not only
focus on a local inflammation or infection but should also regulate a systemic
complex immunologic reaction [35].
As shown in Tables 1, 3, 4 in our series, variables on the first day of ICU
admission, including high APACHE II score, high serum creatinine level, prolonged
prothrombin time and low GCS score, occurrence of septic shock, acute renal failure,
and acute respiratory failure were identified as significant risk factors for mortality.
Based on the multivariate analysis, we only identified presence of acute respiratory
failure requiring mechanical ventilation and the level of APACHE II score > 16 as the
most significant risk factors for predicting mortality. The results were quite different
from previous literature [12-13, 25-26], which demonstrated that septic shock was the
most important risk factors. From our point of view, there were two reasons which
could explain why septic shock was not the most significant risk factors but acute
respiratory failure was in our study. First, even survivors of PLA in our study had a
high incidence of septic shock. Second, based on the improvement of critical care in
management of severe sepsis, some of acute respiratory failure in severe sepsis
patients was averted by early goal-directed resuscitation [36]. As a consequence,
severe sepsis patients who did not progress to acute respiratory failure by aggressively
intensive care had a significantly excellent outcome. The changes perhaps indicated
that an integrated systemic and intensive management would alter the parameters of
risk factors. Certainly our results and explanations need further larger series studies to
confirm our results in the future [12-13, 25-27].
APACHE II score had been useful for predicting outcome of ICU admissions in
many investigations [37]. However, rare studies reported that it was an independent
risk factor for predicting mortality of PLA patients [38]. It was possible that most
PLA patients were not in ICU setting, so the data of APACHE II was lacking. Another
remarkable finding of the present study was that the overall mortality rate (4.6 %) was
lower than previous reports [8-13, 39], which may reflect the improvement of
intensive care before organ failure and uncontrolled sepsis.
In conclusion, the mortality rate in patients with PLA requiring intensive care
was still high. Klebsiella pneumoniae was the most commonly isolated causative
microorganism and associated septic metastatic infection might occur. Variables
including liver abscess size, pathogens, comorbidity and most laboratory data were
not associated with mortality. Only the presence of acute respiratory failure and
APACHE II score > 16 on the first day of ICU admission were the independent
significant prognostic factors in PLA patient admitted to the ICU.
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Table 1. Clinical Features of Patients with Pyogenic Liver Abscess Admitted to
the ICU
Clinical feature Survivors (n=52)
APACHE= Acute Physiology and Chronic Health Evaluation
Onset of symptoms mean the duration (days) from onset of symptoms to admission Age, Body mass index, and APACHE II score were expressed as mean ± SD All other data were expressed as numbers (percentages)
Table 2. Features of Liver Abscess, Bacteriology, and Treatment of Patients with
Pyogenic Liver Abscess Admitted to the ICU
Variable Survivors Note: data were expressed as numbers (percentages)
Table 3. Laboratory Data of Patients with Pyogenic Liver Abscess on the First
Hemoglobin 11.3±2 10.4±3 0.17
Platelet (103/per mm3) 202±175 196±133 0.89 AST= aspartate aminotransferase BUN=blood urea nitrogen ALT=alanine aminotransferase
Data were expressed as mean ± standard deviation
Table 4. Complication and Outcome of Patients with Pyogenic Liver Abscess
Hospital stay, (days) 30±17 34±68 0.64
ICU stay, (days) 10±10 10±11 0.89
DIC= disseminated intravascular coagulation
ARDS= acute respiratory distress syndrome ICU= intensive care unit Data were expressed as numbers (percentages)
Hospital stay and ICU stay were expressed as mean ± SD
Table 5. Multiple Logistic Regression Analysis of Prognostic Factors for 72
Patients with Pyogenic Liver Abscess Admitted in ICU
Factors Comparison Relative risk (95% CI) p value Septic Shock yes vs. no 0.21 (0.02~2.2) 0.194 Acute Respiratory failure yes vs. no 18.7 (2.7~125.2) 0.003 Acute Renal failure yes vs. no 1.44 (0.27~7.69) 0.667 APACHE II >16 vs. ≦ 16 7.43 (1.27~43.4) 0.026 Note: APACHE = Acute Physiology and Chronic Health Evaluation