Primary postpartum hemorrhage (PPH) is a major cause of maternal morbidity and one of the top five causes of maternal mortality in both developed and developing countries (1). Primary PPH can be classified into grades of severity, relating to the amount of blood actually lost by the patient. However, previous studies showed that blood loss estimation by obstetricians had been found to be neither precise nor accurate (2–4). Also recent studies showed that emergency department (ED) physicians did not estimate blood loss well in variety of scenarios, and such estimates could potentially be misleading if used in clinical decision making (5, 6). Especially, in the ED setting, it will be more difficult to estimate blood loss for clinicians attending to patients with primary PPH who transferred from other hospitals.
However, the prompt and objective recognition of patients at risk for severe hemorrhage shock, i.e., those who require massive transfusion (MT) during the immediate phase of resuscitation, is very important to optimize patient outcomes.
For trauma patients, it has been known that the severity of hemorrhagic shock can be diagnosed by traditional vital signs, including heart rate (HR), blood pressure (BP), pulse pressure, respiration rate, urine output, and mental status. Systolic BP (SBP) has been used as the most common triage parameter in the ED setting, even though hypotension has long been stated to be a late finding of shock (7). However, many studies reported that the traditional vital signs alone are not reliable measures of acute hemorrhage because compensatory mechanisms and shock index (SI), defined as the ratio of HR to SBP, better identify patients with early acute blood loss rather than traditional vital signs (8–12).
We hypothesized that initial SI, available on arrival to the ED, could be predictive of the requirement for MT in ED patients with primary PPH. The aim of this study was to determine whether initial SI was independently associated with the requirement for MT in ED patients with primary PPH.
MATERIALS AND METHODS
This retrospective cohort single-center study was conducted at the Asan Medical Center, a 2,800-bed, university-affiliated, tertiary referral center in Seoul, Korea. The cohort was composed of 126 consecutive primary PPH patients who presented to the ED between January 1, 2004, and May 31, 2012. Primary PPH was defined as blood loss of 500 mL or more that occurs within 24 h after birth. Patients were excluded if they had transfusion of more than 1 U of packed red blood cells (pRBCs) before ED arrival.
This study was approved by the ethics committee of our institution, and the informed consent was waived because of retrospective study.
The clinical and demographic characteristics of all patients, including their age, initial vital signs, and initial laboratory findings, were retrieved from electronic medical records. The amount of transfusion including pRBCs, fresh frozen plasma (FFP), platelet concentrates (PCs) within initial 24 h and during hospitalization and definitive treatment, including embolization and hysterectomy, were also retrieved. Initial vital signs on arrival to ED were used to calculate SI (defined as HR divided by SBP). Data collection was performed using a predrafted data abstraction form by two emergency physicians. Each data abstraction form was verified for completeness and accuracy by one of the two emergency physicians.
Study patients were classified into two groups: MT group defined as patients who required transfusion of 10 U or more of pRBCs within initial 24 h and non-MT group defined as patients who did not.
All statistical analyses were performed using SPSS for Windows version 18.0 (SPSS Inc, Chicago, Ill). The data are presented as median and interquartile range (IQR) for continuous variables and as absolute or relative frequencies for categorical variables. For comparisons of categorical variables, Pearson χ2 test or Fisher exact test was used. Continuous variables were analyzed for normal distribution by the Kolmogorov-Smirnov test, and then either Student t test or Mann-Whitney U test was performed depending on the distribution. Multivariate logistic regression analyses were used to identify independent factors associated with the requirement for MT, and all variables associated with the requirement for MT in univariate analyses were included in the logistic regression analysis. Stepwise modeling was used to screen potential variables for inclusion in the final model. The results of multivariate logistic regression analysis were reported as odds ratios (ORs) and 95% confidence intervals (CIs). SPSS sample power v3 for Windows (SPSS Inc) was used for the calculation of the actual power of this study.
A total of 126 patients were included in this study. Of these patients, 26 (20.6%) were included in MT group and 100 (79.4%) in non-MT group (Fig. 1). The actual power of this study was 0.97. Baseline and clinical characteristics of patients classified according to the requirement for MT are summarized in Table 1. There were no significant differences in age, parity, the type of delivery, and the time interval between the onset of bleeding and arrival at the ED between two groups. However, there was a significant difference in initial mental status between two groups (P < 0.01). Patients in MT group had significantly lower SBP, lower diastolic BP (DBP), and higher HR on arrival to ED compared with patients in non-MT group. The hypotensive state (defined as SBP <90 mmHg) on arrival to the ED was more frequent in MT group than in non-MT group (30.8% vs 11.0%, P = 0.03). Initial SI on arrival to the ED was significantly higher in MT group than in non-MT group (1.3 vs 0.8, P < 0.01).
Laboratory findings, transfusion, definitive treatment, and outcome according to the requirement for MT are compared in Table 2. Patients in MT group had significantly lower hemoglobin, lower hematocrit, lower platelet counts, and prolonged prothrombin time international normalized ratio compared with patients in non-MT group. Units of blood components including pRBCs, FFP, and PCs are compared in Table 2. Patients in MT group had significantly more units of blood components compared with patients in non-MT group. Also patients in MT group had increased length of stay, higher intensive care unit care, and higher in-hospital mortality compared with patients in non-MT group (P < 0.01). Of fatalities, two patients died of cardiac arrest due to uncontrolled hemorrhagic shock, and one patient died of multiple organ dysfunction syndrome after severe hemorrhagic shock.
Initial mental status, SBP, hypotensive state, DBP, HR, and SI that were statistically significant in the univariate analysis were included in multivariate logistic regression analysis. Initial SI and HR were the only variables associated with the requirement for MT, with ORs of 9.47 (95% CI, 1.75–51.28; P < 0.01) and 1.06 (95% CI, 1.02–1.09; P < 0.01), respectively (Table 3).
In the normal SI group (0.5 ≤ SI < 0.7), MT rate was 0.0% (Fig. 2). As SI increased above 0.7, an increase in MT rate was observed, and in the group with SI of 1.3 or greater, 66.7% required MT.
In this study, we identified that initial SI was independently associated with the requirement for MT in ED patients with primary PPH. This finding suggests that simple calculation of SI from initial vital signs on arrival to the ED provides very useful information about timely and appropriate use of MT to improve clinical outcomes in patients with primary PPH in the ED setting.
To the best of our knowledge, this is the first study to evaluate the potential utility of initial SI to guide MT therapy during the immediate phase of resuscitation for ED patients with primary PPH.
Resuscitation of patients with primary PPH is conceptually similar to that of patients with traumatic injury, where the goals are to establish rapid control of bleeding and restore systemic oxygen delivery (13). Resuscitation of patients with traumatic injury is defined as two phases: an immediate phase directly after injury with ongoing hemorrhage and a maintenance phase after stabilization (14). During the immediate phase of resuscitation, rapid restoration of the components of the blood including pRBCs and PCs is essential for ensuring adequate tissue perfusion, i.e., systemic oxygen delivery, and preventing acidosis, coagulopathy, and hypothermia. Also, adequate replacement of plasma component including FFP is particularly important for avoiding dilutional coagulopathy in the patient with massive bleeding (13). For patients with major gastrointestinal bleeding, surgery, or trauma, the availability of MT protocol, which comprises a prepared package of pRBCs and other blood products, can prove lifesaving in the management of severe hemorrhage (15). But rapid identification of patients’ active ongoing bleeding requiring transfusion or even MT remains unsatisfactory (16). Recently, two studies showed that the implementation of a standardized MT protocol achieved in part the optimization of outcomes of patients with life-threatening primary PPH (13, 17). But, there were no strict criteria for activating MT protocol, and the decision was based on the rate/magnitude of ongoing blood loss, a high index of suspicion for the development of major hemorrhage, the lack of availability of cross-matched blood, and the early response to medical/surgical intervention (17). However, it is very difficult and inaccurate to predict blood loss for clinicians attending to patients with acute hemorrhage (2–6). Especially, in the ED setting, it will be more difficult to estimate blood loss for clinicians attending to patients with primary PPH who transferred from other hospitals.
Charbit et al. (18) reported that early changes in the coagulation profile occur during the early period of blood loss, including decreased fibrinogen, factor V, antithrombin, and protein C and increased PT and thrombin-antithrombin levels in patients who develop severe PPH. The results of laboratory coagulation testing such as prothrombin time, activated partial thromboplastin time, platelet counts, and fibrinogen are best used to guide blood products replacement therapy during the maintenance phase of resuscitation for patients with primary PPH (13). However, standard coagulation tests are usually unavailable during the immediate phase of resuscitation in the ED because they have typical turnaround times around 30 to 60 min or longer (19, 20).
In the ED setting, clinicians use SBP as the most common parameter for predicting the severity of acute hemorrhage. But patients with occult shock, whose compensatory mechanisms are maintaining adequate SBP, may be undertriaged and have significant delay to appropriate care (7, 21).
When PPH is excessive, a syndrome of hypovolemic shock occurs, characterized by inadequate blood flow to vital organs, and specifically the change in mental status occurs when blood loss exceeds about 1,000 to 2,000 mL (22). In the present study, the change in mental status was more frequent in the MT group than in the non-MT group. However, in multivariate analysis, there was no statistically significant difference between two groups.
Shock index is a simple calculation of HR divided by SBP. Shock index is normally 0.5 to 0.7 and has been shown to be elevated in the setting of acute hypovolemia and left ventricular dysfunction (11, 23–25). The critically ill patient demonstrates a physiological compensatory mechanism, keeping the BP from falling despite the presence of decreased circulating blood volume, stroke volume, and cardiac output (26). In such situations, SI can serve well as an early warning predictor as compared with the conventional vital signs. The utility of SI has been evaluated as a predictor of ruptured ectopic pregnancy, ongoing intraoperative bleeding, the need for expedient intervention in gastrointestinal hemorrhage, sepsis, and the differentiation of major and minor injury (24, 26–32). Also, according to a study by Choi et al. (33), SI was a better marker for predicting mortality in rats undergoing acute hemorrhage in comparison to the traditional vital signs including SBP, DBP, and HR.
However, to date, the usefulness of SI has not been specifically examined in patients with primary PPH. In our study, SI was independently associated with the requirement for MT. Because vital signs are measured immediately in all patients on arrival to the ED and before the initiation of resuscitation, SI is easily available during the immediate phase of ED resuscitation. Thus, clinicians attending to patients with primary PPH in the ED can use initial SI as a predictor of the requirement for MT during the immediate phase of resuscitation.
Our study has several limitations. First, this study was limited by its retrospective design, with all of the potential errors inherent to this type of study. Second, we analyzed only patients who presented to the ED. Thus, it would be difficult to apply our results to patients in the labor and delivery unit of hospital or the obstetric clinic. Third, in our study, patients were excluded if they had transfusion of more than 1 U of pRBCs before ED arrival from other hospital. Thus, our results cannot apply to patients who had a transfusion before ED arrival. Based on these data, we recommend additional prospective studies to confirm out results.
In conclusion, initial SI was independently associated with the requirement for MT in ED patients with primary PPH. This finding suggests that simple calculation of SI from initial vital signs on arrival to the ED can help clinicians to identify PPH patients who may benefit from timely and appropriate use of MT to improve clinical outcomes.
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