The treatment effects of Xuebijing (XBJ) injection in severe septic patients with disseminated intravascular coagulation (DIC) were investigated in this study. 171 severe septic patients with DIC were divided into the control group (
Despite advancements in modern antibiotics and supportive therapies, the mortality of severe sepsis remains high. In the United States, severe sepsis accounts for 751,000 hospital admissions and 215,000 deaths every year, with an in-hospital mortality of 28.6% [
Current management of DIC relies on treating the underlying disease aggressively, along with supplementary therapy with clotting factors and platelets as required [
Xuebijing (XBJ) injection is an intravenous preparation made from five traditional Chinese medicines, namely, Chishao (Radix Paeoniae Rubra), Danggui (Radix Angelica Sinensis), Chuanxiong (Rhizoma Chuanxiong), Honghua (Flos Carthami), and Danshen (Radix Salviae Miltiorrhizae). The bioactive roles of XBJ injection include activating circulation, removing blood stasis, and clearing away toxins [
Although the effects of XBJ injection for treating sepsis have been established, there are few studies on XBJ injection in DIC. Some studies have shown that XBJ injection is also effective in treating patients with DIC [
This study included 171 adult severe septic patients with DIC who were admitted to the emergency intensive care unit (EICU) of Beijing Chaoyang Hospital, which is an urban, university hospital, from January 2011 to December 2011. Exclusion criteria were as follows: age <18 years, survival time <7 days after EICU admission, previous history of coagulopathy, use of anticoagulants, pregnancy, or breast feeding.
According to the criteria of the 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference [
DIC was diagnosed according to the criteria of the International Society on Thrombosis and Haemostasis Subcommittee. Platelet count, prothrombin time (PT), fibrinogen, and D-dimer levels were used to calculate the DIC score, and a score ≥5 was considered compatible with overt DIC (Table
ISTH scoring system for overt DIC.
0 | 1 point | 2 points | 3 points | |
---|---|---|---|---|
Platelet (×109/L) | ≥100 | <100 but ≥50 | <50 | |
Prolongation of PT | ≤3 sec | >3 sec but ≤6 sec | >6 sec | |
Fibrinogen (g/L) | ≥1.0 | <1.0 | ||
D-dimer (mg/L) | ≤0.4 | >0.4 but ≤4 | >4 |
ISTH: International Society on Thrombosis and Haemostasis; DIC: disseminated intravascular coagulation; PT: prothrombin time.
As this was a retrospective study, ethical approval and informed consent were not necessary according to the Institutional Review Board of Beijing Chaoyang Hospital. The available database of laboratory parameters and the clinical database of our EICU were used in this study.
The mainstays of routine treatments for severe septic patients with DIC were antibiotics, fluid resuscitation, mechanical ventilation, vasoactive agents, nutritional support, and transfusion of blood products, whereas coagulation inhibitors and anticoagulants were not used in our EICU. Patients were divided into the control group or intervention group. For patients in the control group, only routine treatments were administered. For patients in the intervention group, besides routine treatments, 100 mL XBJ injection (Tianjin Chasesun Pharmaceutical Co., Ltd., Tianjin, China) with 100 mL normal saline was administered via intravenous drip twice daily for 7 consecutive days. XBJ injection was administered separately, and 50 mL normal saline was used to wash the pipeline before and after administration of XBJ injection. Therefore, XBJ injection did not interact with other routine medicines.
The primary efficacy endpoint was incidence of DIC as evaluated at 7 days after administration of XBJ injection. Other evaluation parameters were as follows: (1) clinical severity scores, including the Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation (APACHE) II score; (2) coagulation parameters, including platelet, PT, fibrinogen, D-dimer, and INR; and (3) differences of clinical severity scores and coagulation parameters (values at baseline minus values at 7 days after administration of XBJ injection).
Nine variables of the MEDS score were as follows: terminal illness, tachypnea or hypoxia, septic shock, low platelet count, bandemia, age >65 years, lower respiratory tract infection, nursing home resident, and altered mental status. The MEDS score was calculated by summing the points of nine variables, giving a possible score of 0 to 27 [
The APACHE II score comprised weightings for temperature, mean arterial pressure, heart rate, respiratory rate, oxygenation, arterial pH, sodium, potassium, creatinine, hematocrit, white blood cell count, Glasgow coma score, age, chronic diseases, and surgical status, giving a possible score of 0 to 71 [
PT, INR, fibrinogen, and D-dimer levels were measured on sodium citrate anticoagulated samples using Sysmex CA7000 blood coagulation analyzer (Sysmex Corporation, Kobe, Japan). PT, INR, and plasma fibrinogen levels were measured with coagulation-based activity assay. Plasma D-dimer levels were measured with the method of immunoturbidimetric assay. Platelet count was measured on EDTA anticoagulated samples with the method of fluorescent dye laser scattering using XE-2100 blood analyzer (Sysmex Corporation, Kobe, Japan).
Evaluation parameters of side effects of XBJ injection included (1) changes in vital signs; (2) complete blood cell count and urine routine examination; and (3) biochemical parameters, including hepatic function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin), renal function (blood urea nitrogen and creatinine), glucose, and electrolytes.
The primary outcome of this study was all-cause 28-day mortality, and the survival or death of patients within 28 days was recorded.
The results were analyzed with SPSS 16.0 software (SPSS Inc., Chicago, IL, USA). Normally distributed data were expressed as the mean ± standard deviation and nonnormally distributed data were expressed as the median (25–75th percentiles). The Student paired
This study included 171 severe septic patients with DIC: 83 patients in the control group and 88 patients in the intervention group. The baseline characteristics of the overall study population are shown in Table
Baseline characteristics of patients.
Control group ( |
Intervention group ( |
| |
---|---|---|---|
Age (yrs) | 56 (49–73) | 59 (53–74) | 0.14 |
Male ( |
51 (61.45) | 57 (64.77) | 0.652 |
BMI |
|
|
0.158 |
28-day mortality ( |
29 (34.94) | 18 (20.45) | 0.034 |
Platelet (×109/L) |
|
|
0.326 |
PT (s) |
|
|
0.263 |
Fibrinogen (g/L) |
|
|
0.17 |
D-dimer (mg/L) | 4.7 (1.85–8.62) | 5.2 (2.12–9.53) | 0.192 |
INR |
|
|
0.607 |
MEDS score | 11 (8–19) | 12 (9–21) | 0.794 |
APACHE II score | 24 (15–32) | 26 (16–35) | 0.334 |
Type of infection ( |
|||
Pneumonia | 39 (46.88) | 49 (55.68) | 0.256 |
IAI | 37 (44.58) | 33 (37.5) | 0.347 |
USI | 7 (8.43) | 6 (6.82) | 0.69 |
BMI: body mass index; PT: prothrombin time; INR: international normalized ratio; MEDS score: Mortality in Emergency Department Sepsis score; APACHE II score: Acute Physiology and Chronic Health Evaluation II score; IAI: intra-abdominal infection; USI: urinary system infection.
Compared with the control group, incidence of DIC in the intervention group was significantly lower at 7 days after administration of XBJ injection (
Incidence of DIC, clinical severity scores, and coagulation parameters at 7 days after administration of Xuebijing injection.
Control group ( |
Intervention group ( |
| |
---|---|---|---|
DIC ( |
22 (26.51) | 5 (5.68) | <0.001 |
Platelet (×109/L) |
|
|
0.205 |
PT (s) |
|
|
0.003 |
Fibrinogen (g/L) |
|
|
0.183 |
D-dimer (mg/L) | 3.72 (1.26–6.37) | 3.45 (1.12–5.87) | 0.743 |
INR |
|
|
0.997 |
MEDS score | 8 (5–18) | 7 (4–15) | 0.039 |
APACHE II score | 14 (11–27) | 13 (10–25) | 0.107 |
DIC: disseminated intravascular coagulation; MEDS score: Mortality in Emergency Department Sepsis score; APACHE II score: Acute Physiology and Chronic Health Evaluation II score; PT: prothrombin time; INR: international normalized ratio.
Compared with the control group, the MEDS score was lower in the intervention group (
Differences of the MEDS score and APACHE II score were greater in the intervention group than in the control group (
Differences of clinical severity scores and coagulation parameters (values at baseline minus values at 7 days after administration of Xuebijing injection).
Control group ( |
Intervention group ( |
| |
---|---|---|---|
Platelet (×109/L) |
|
|
0.005 |
PT (s) |
|
|
0.036 |
Fibrinogen (g/L) |
|
|
0.563 |
D-dimer (mg/L) |
|
|
0.138 |
INR |
|
|
0.472 |
MEDS score |
|
|
0.007 |
APACHE II score |
|
|
0.014 |
MEDS score: Mortality in Emergency Department Sepsis score; APACHE II score: Acute Physiology and Chronic Health Evaluation II score; PT: prothrombin time; INR: international normalized ratio.
Compared with the control group, 28-day mortality was significantly lower in the intervention group (
There were no records of side effects during administration of XBJ injection.
The main findings of this study were as follows: (1) compared with the control group, incidence of DIC was significantly lower in the intervention group at 7 days after administration of XBJ injection; and (2) 28-day mortality was significantly lower in the intervention group than in the control group.
XBJ injection is a compound preparation made from five traditional Chinese medicines. Consistency in the quality of XBJ injection among different batches is ensured by fingerprint technology, which refers to the use of spectroscopy and chromatography to obtain the characteristics of component groups, maps, or images, combined with computer technology to analyze information, thereby identifying the authenticity of the drugs [
Currently, there are few studies on XBJ injection for treating DIC. Furthermore, the dose and time of XBJ injection in previous studies were not uniform. The report of Guo et al. included 4 patients with DIC, among whom two received 100 mL XBJ injection twice daily, one received 100 mL XBJ injection once daily, and one received 200 mL XBJ injection twice daily [
It has been recognized that the crosstalk between inflammation and coagulation is important in the pathogenesis of sepsis, and endothelium is the central link. During sepsis, inflammatory mediators cause endothelial damage, and damaged endothelium manifests enhanced procoagulatory properties and leads to coagulation activation; vice versa coagulation activation enhances inflammatory responses. DIC is the most severe form of coagulation abnormalities and its development is closely associated with endothelial damage [
The MEDS score and APACHE II score at baseline were not significantly different between the two groups (Table
28-day mortality in the intervention group and control group was 20.45% and 34.94%, respectively. It is notable that 28-day mortality was significantly lower in the intervention group (Table
An important limitation of this study is the retrospective design. Although the data were analyzed on the basis of laboratory parameters at entry and after treatments, this type of analysis should always be interpreted with care. Another important limitation is that this was a single-center study, and the results may not be applicable to other hospitals. Therefore, a prospective, multicenter, randomized controlled trial is needed to further confirm the effects of XBJ injection in severe septic patients with DIC in future research.
In conclusion, this study demonstrates that XBJ injection can effectively treat DIC caused by severe sepsis and improve short-term prognosis of severe septic patients with DIC.
The authors declare that there is no conflict of interests regarding the publication of this paper.