We retrospectively analyzed data of 70 patients who were consecutively admitted to ICU of Eulji Universivy Hospital, Daejeon, Republic of Korea and diagnosed with scrub typhus between May 2004 and December 2014. The diagnosis of scrub typhus was based on the World Health Organization's criteria7. When an immunofluorescent antibody assay (IFA) titer against O. tsutsugamushi increased more than four times or an indirect IFA IgM titer against O. tsutsugamushi to ≥1:80, scrub typhus was confirmed.

The following data were collected from medical records: age, gender, vital signs, months at admission, reasons for ICU admission, comorbidities, symptoms, and laboratory findings at admission, transfusion, inotropic agent, eschar, death, cause of death, total duration of hospitalization, duration of ICU stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score.

In this study, we divided study patients into the following two groups: the mechanical ventilation group (MV group) and the non-mechanical ventilation group (non-MV group). We considered mechanical ventilation if patients were treated with mechanical ventilation, whether the time of diagnosis was before or after mechanical ventilation. Sepsis was defined by the present of both infection and systemic inflammatory response syndrome (SIRS). SIRS was considered if patients fullfilled at least two of the following criteria: body temperature <36℃ or >38℃, heart rate >90 beats per minute, respiratory rate >20 breaths per minute, leukocyte count <4,000 or >12,000 cells/µL or the presence of more than 10% band forms. Neurologic problem was defined by the presence of central nervous system (CNS) related symptoms such as confusion, seizure, or coma. Acute respiratory failure was defined not only by the result that hypoxemia, hypercapnia, or both cannot be maintained within normal ranges, but also by the presence of symptoms and signs resulted in the need for mechanical ventilation, pneumonia, pleural effusion, pulmonary edema, or acute respiratory distress syndrome. Cardiac problem was defined by the presence of symptoms and signs result in pericardial effusion, ischemic heart failure, and arrhythmia such as atrial fibrillation, ventricular tachycardia, and complete atrioventicular block. Acute renal failure was defined as at least 50% reduction in glomerular filtration rate using the abbreviated modified diet in renal disease equation.

Continuous variables were compared using the two-tailed Student's t test. Categorical data were analyzed using the chi-square test. Factors associated with mechanical ventilation were analyzed by binary linear regression models. Univariate binary logistic regression analysis was done. Then, multivariate analysis was done with the significant factors in the univariate analysis. Results were reported as mean±standard deviation or number (%). Data was collected in Microsoft EXCEL (Microsoft Excel 2007; Microsoft Corp., Seattle, WA, USA) and all statistical analysis were performed using SPSS version 14.0 (SPSS Inc., Chicago, IL, USA). All p-values were 2-tailed and statistical significance was considered when p-value was less than 0.05.

This study was conducted in compliance with the World Medical Association Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Eulji University Hospital (IRB File No. EMC 2014-08-007). Informed consent was waived by the board.

A total of 70 patients, 32 (45.7%) were males, 15 (21.4%) had rash, 35 (50.0%) had eschar, and seven (10%) were dead. The mean age of patients was 71.2±11.1 years (Table 1). The antibiotic treatment between 69 patients and one non-mechanical ventilation patient were doxycycline and flumoxef plus clarithromycin, respectively. The most common reasons of the patients admitted to ICU were acute respiratory failure in MV group and sepsis in non-MV group. Statistically significant differences were observed in acute respiratory failure between the two groups (p=0.008). Clinical features were analyzed between MV group and non-MV group (Table 1). The mean of peak airway pressure, positive end-expiratory pressure, fraction of inspired oxygen (FiO₂), and tidal volume in MV group were 14.6±3.2 mm Hg, 5.6±3.8 mm Hg, 71.6±21.2%, and 437.4±68.7 mL, respectively. There were statistically significant differences in APACHE II score (p=0.015), and death (p=0.014) between two groups. In comparison of laboratory features between two groups, there was no statistically significant difference (Table 2).

We analyzed factors associated with mechanical ventilation in the patients with scrub typhus admitted to ICU. In univariate analysis, acute respiratory failure at admission to ICU (p=0.005), APACHE II score (p=0.017), SOFA score (p=0.020), platelet count (p=0.058), and lactate dehydrogenase (LDH) (p=0.074) were statistically significant factors (Table 3). In multivariate analysis, acute respiratory failure at admission to ICU (odds ratio [OR], 6.289; 95% confidence interval [CI], 1.517-26.071; p=0.011), SOFA score (OR, 1.453; 95% CI, 1.119- 1.888; p=0.005), APACHE II score (OR, 1.187; 95% CI, 1.040- 1.353; p=0.011), platelet count (OR, 1.010; 95% CI, 1.002-1.017; p=0.009), and LDH (OR, 1.002; 95% CI, 1.000-1.003; p=0.011) were independent significant factors associated with mechanical ventilation in the patients with scrub typhus admitted to ICU (Table 3).

We analyzed various periods of the patients with scrub typhus between MV group and non-MV group. There was statistically significant differences in the duration of ICU stay between two groups (p=0.028). However, there were no statistically significant differences in the duration of hospitalization, and doxycycline treatment before admitting to ICU between two groups (Table 4).