CN112669965A

CN112669965A - Sepsis prognosis evaluating system

Info

Publication number: CN112669965A
Application number: CN201910987358.0A
Authority: CN
Inventors: 曹钰; 李东泽; 姚蓉; 王婉婷; 何亚荣
Original assignee: West China Hospital of Sichuan University
Current assignee: West China Hospital of Sichuan University
Priority date: 2019-10-16
Filing date: 2019-10-16
Publication date: 2021-04-16

Abstract

The invention provides a sepsis prognosis evaluation system, which carries out sepsis pre-hospital prognosis evaluation by information such as age, heart rate, respiratory rate and whether consciousness disorder exists. The sepsis patients graded by the system have significant differences in 7-day fatality rate, 28-day mechanical ventilation rate and 28-day ICU survival rate. The evaluation system of the invention can rapidly and accurately guide sepsis risk classification, and has very good application prospect.

Description

Sepsis prognosis evaluating system

Technical Field

The invention belongs to the field of pre-hospital prognosis evaluation, and particularly relates to a sepsis prognosis evaluation system.

Background

Sepsis (Sepsis) is a clinical syndrome in which the host response to infectious disorders causes life-threatening organ dysfunction, with high mortality and increasing incidence year by year. In the United states, 7.5 hundred million hospitalized patients are in total in 1979 to 2000, wherein 10,319,418 patients with sepsis have an annual incidence increased from 16.4 to 66 ten thousand, and the annual growth rate is 9%. The mortality rate of sepsis is between 30% and 50%, and has declined in recent years as the level of awareness of medical personnel of sepsis has increased. But since the early clinical manifestations of sepsis are not specific, multiple organ systems are involved. Patients with sepsis have a great individual variability, and if septic shock is not recognized in time, the mortality rate of patients with sepsis is obviously increased. Every hour of delay to start treatment after diagnosis, sepsis-associated mortality increases by approximately 8%. The 2016 renewed rescue Sepsis Campaign (SSC) indicated that early and timely effective intervention in individualized treatment of Sepsis patients is a powerful measure to improve the prognosis of Sepsis patients. Therefore, early identification of sepsis patients with high mortality risk and timely intervention are of great significance in clinical work. A prognostic scoring system that simply quantifies the risk of patient death is needed to help clinicians identify the patient's criticality early and guide clinical decisions.

The scores currently widely used clinically to assess the prognosis of patients with sepsis are mainly acute physiology and chronic health condition score system (APACHE) II, sequential organ failure Score (SOFA), rapid sequential organ failure score (qsfa), improved early warning score (MEWS), and sepsis-related mortality score in emergency department (MEDS). Early Systemic Inflammatory Response Syndrome (SIRS) scores do not fully reflect a deregulated host Response, many other patients with no infection or poor prognosis meet the SIRS score criteria, while ICU severely infected patients at 1/8 do not meet the SIRS score criteria of 2 or more, and thus SIRS is currently used less clinically to assess the prognosis of sepsis patients. The APACHE II and SOFA scores can accurately reflect the prognosis of patients with sepsis, the infection or suspected infection plus SOFA more than or equal to 2 points is recommended to define the sepsis in the current definition of international third edition sepsis and septic shock (sepsis3.0), but the two scores are complex in index required for calculation, part of blood indexes are difficult to measure in the early stage of emergency treatment, and the early shunting of the emergency treatment is not facilitated. MEDS, mems are somewhat simpler to calculate than the first two, but are not as sensitive and specific as the first two, and do not guide early clinical decisions in emergency. qSOFA only consists of systolic pressure less than or equal to 100mmHg, respiratory frequency more than or equal to 22 times per minute and disturbance of consciousness, is simple to calculate and is suitable for quick screening beside a bed. However, the low sensitivity of the qSOFA prognostic assessment (New Sepsis criterion: A Change We Shuold Not Make. Chest2016, 149 (5): 1117-; also, researchers have indicated that qsfa has not been supported by critical evidence-based medical evidence, but has been clinically abused to guide clinical decisions; in addition, studies have shown that qSOFA is not as desirable in assessing mechanical ventilation and organ function recovery in septic patients (compare of qSOFA and SIRS for predicting both ventilation and organ function of patients of sepsis. critical care (London, England)2017, 21 (1): 73.).

At present, a sepsis patient prognosis scoring system with simple index parameters and high accuracy is lacked.

Disclosure of Invention

In order to solve the above problems, the present invention provides a sepsis prognosis evaluation system, which comprises an input module, a scoring module, a diagnosis module and an output module;

the input module is used for receiving information such as the age, heart rate, respiratory rate and whether consciousness disorder exists of the sepsis patient;

the scoring module receives information from the input module and scores according to the Pre-hospital Prognostic Prediction Score (PPS) rule of the present invention:

1) age: the number is less than 46 years old, and the score is 0; 46-59 years old, count 3 points; 60-71 years old, 4 points are counted; 5 points are counted when the Chinese medicinal composition is older than 71 years;

2) heart rate: less than 95 times/minute, and 0 minute is counted; 95-107 times/minute, 3 minutes; 108-; 3 minutes is counted when the time is more than 123 times/minute;

3) breathing frequency: less than 21 times/minute, and 0 minute is counted; 21-22 times/minute, and 1 minute is counted; 23-25 times/minute, 2 minutes; more than 25 times/minute, 6 minutes are counted;

4) disturbance of consciousness: judging that the consciousness disturbance is judged if the Glassy coma score is less than or equal to 14 points, and counting 7 points if the consciousness disturbance is judged; if the patient is unconscious, the score is 0;

5) summing the four fractions to obtain a total fraction;

the diagnosis module is responsible for obtaining a diagnosis conclusion according to the total score given by the scoring module according to the following rules:

(1) when the total score is 0-6, the diagnosis is concluded as: low risk;

(2) when the total score is 7-9 minutes, the diagnosis is concluded as: medium risk;

(3) when the total score is more than 10 points, the diagnosis conclusion is that: high risk;

the output module is responsible for outputting the diagnosis conclusion.

Further, the output module also outputs the total score and/or each score value obtained by the scoring module.

Further, the disturbance of consciousness is: lethargy, light coma, moderate coma or deep coma.

Note: the glasgow coma score is also called the glasgow coma index, and is scored from three aspects of eye opening reaction, language reaction and limb movement, the total score of the three aspects is the glasgow coma score, and the scoring standards of the three aspects are as follows:

1. eye reaction (E, Eye openning)

And 4, dividing: open eyes naturally (spontaneous): when the patient is close to the patient, the patient can open the eyes automatically, and the operator should not speak and touch the patient.

And 3, dividing: call eyes open (to speech): a normal volume call to the patient, or a high volume call, does not contact the patient.

And 2, dividing: eye irritation or pain (to pain): the patient is tapped or shaken first, and is given a strong stimulus after no response, such as: the lateral side of the 2 nd or 3 rd finger of the patient is stimulated by a pen tip, the stimulation is increased to the maximum within 10 seconds, the eyes are strongly stimulated to open, and the score is 2, and if the eyebrows are wrinkled, the eyes are closed, and the expression is painful, the score cannot be 2.

1 minute: no response to stimulation (none)

2. Language reaction (V, Verbal response)

And 5, dividing: justification of speech (ordered): the orientation capability is correct, and the name, the city or the current place, the year and the month of the year can be clearly expressed.

And 4, dividing: (ii) answered, but not asked questions (conflicted): disorientation and wrong answer.

And 3, dividing: the single word (inperpropriates words) can be said to be: no dialogue can be done at all, only short sentences or single words can be said.

And 2, dividing: utterances (unidentifiable voices): only meaningless screaming sounds can be made to the painful stimuli.

1 minute: without any reaction (none).

3. Limb movement (M, Motor response)

6 min: actionable on command (obey commands): 2 different actions are accomplished per instruction.

And 5, dividing: the location of the pain (locus) can be located when a stimulus is applied: in the case of painful stimuli, the patient can move the limb in an attempt to remove the stimulus. Pain stimulation was gold standard with supraorbital nerve compression.

And 4, dividing: in response to a painful stimulus, the limb will retract (withdry).

And 3, dividing: in response to painful stimuli, the limb bends (decortite flexion): takes on the posture of 'decortication and tetany'.

And 2, dividing: in response to painful stimuli, the limb straightens (deceibrate extension): takes on the posture of 'eliminating rigidity of brain'.

1 minute: without any reaction (no response).

The invention has the following beneficial effects:

1) the system disclosed by the invention can realize sepsis prognosis risk assessment by only detecting the heart rate and the respiratory rate and combining the age and whether the consciousness disorder is disturbed or not without using a complex instrument, is simple and quick, and is convenient for helping clinicians and even non-medical professionals to quickly and accurately identify high-risk sepsis patients in the early stage of hospital or emergency treatment.

2) The system of the invention has high diagnosis accuracy: a) the area under the curve (AUC) of 28-day disease death evaluated by the score is 0.762, which is higher than APACHE II, MEDS and qSOFA and is not inferior to the existing SOFA and APACHE II; b) the area under the curve for assessing 7-day mortality was 0.777, higher than SOFA, MEDS, MEWS, and qsfa; c) AUC for the 28-day mechanical ventilation evaluated was 0.718, higher than APACHE II, MEDS, MEWS, and qsfa; d) the AUC for the 28-day occupancy ICU was estimated to be 0.701, higher than APACHE II, MEDS, MEWS, and qsfa.

3) The system of the invention is higher than SOFA and APACHE II in the aspect of predicting 28-day mortality rate differentiation of sepsis.

4) The system can independently predict sepsis prognosis in subgroups of different sexes, ages, white blood cell numbers, platelet numbers, lactic acid concentrations, SOFA scores, APACHE II scores, consciousness states, mechanical ventilation, vascular medicine application and the like.

Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.

The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.

Drawings

FIG. 1: test group HL test.

FIG. 2: validation group PPS, SOFA, APACHE II scores decision analysis curves to predict 28-day mortality from sepsis.

Detailed Description

Example 1 use of the system of the invention

The operator only needs to input the age (year), heart rate (times/minute), respiratory rate (times/minute) and whether the consciousness disorder appears in the sepsis patient through the input module.

The occurrence of disturbance of consciousness specifically means: the cognitive and cognitive abilities of the surrounding environment and the state of the person caused by the impaired activity of the higher nerve center are impaired, such as one of sleepiness, coma, light coma, moderate coma and deep coma.

The scoring module of the system of the present invention will score according to the following criteria:

the scoring module receives information from the input module and scores according to the PPS rule of the invention:

4) disturbance of consciousness: if the consciousness is disturbed, 7 points are counted;

5) summing the four fractions to obtain a total fraction;

the diagnosis module obtains a diagnosis conclusion according to the total score given by the scoring module according to the following rules:

(1) when the total score is 0-6, the diagnosis is concluded as: low risk;

and after the diagnosis module obtains the diagnosis conclusion, the output module outputs the diagnosis conclusion.

The present invention will be further described below by way of examples.

Study subjects involved in the experimental examples:

month 7, 2015, day 1, 00: 6 months and 30 days from 00 to 2016 23: sepsis was diagnosed in the emergency department at western university, washington, 59 days, and 841 patients who met the inclusion criteria and did not meet the exclusion criteria. Patients were randomized into trial (n-585) and validation (n-236) groups, with no statistical difference in the general data, site of infection, vital signs, laboratory examination, and incidence of endpoint events (P > 0.05). Inclusion and exclusion criteria are as follows:

inclusion criteria were: (the following 2 items should be satisfied at the same time)

Meeting the sepsis diagnosis standard: reference to sepsis septic shock definition version 3 [17 ]: sepsis patients infected or suspected to be infected and having a SOFA score of greater than or equal to 2 points; ② the age is more than or equal to 18 years old;

exclusion criteria: (satisfy any one of them and exclude them)

The test is not willing to be added; ② pregnancy; history of severe organ dysfunction; thrombotic or connective tissue disease; fifthly, merging basic diseases of the blood system; sixthly, mechanical ventilation (including wound and non-wound) is performed when the hospital arrives; seventhly, when the emergency treatment is reached, sudden cardiac arrest occurs and immediate resuscitation is needed; the diagnosis of the blood vessel is carried out for 2 weeks, and the history of anticoagulation and anti-platelet treatment is available; and ninthly, the data are not complete and cannot be scored or are not complete within 24h of admission.

Indices collected for study subjects:

1) general data: sex, age, time of onset, site of infection, history of present disease, past history, etc.;

2) vital signs: heart rate, body temperature, blood pressure, respiratory rate, state of consciousness, etc. at the time of visit;

3) laboratory metrics including: blood routine (white blood cell count, hemoglobin, platelet count, etc.); ② blood biochemistry (total bilirubin, urea nitrogen, serum creatinine); DIC conventions (D-dimers, fibrinogen, etc.); inflammation indexes (PCT, IL-6, CRP and the like); analysis of arterial blood gas (PH, PO2, PCO2, FiO2, plasma lactic acid, etc.); sixthly, lactic acid and the like;

4) scoring of the disease is done based on the data collected (see tables 1-6, attached below), including: glasgow Coma Score (GCS), APACHE II score, SOFA score, qsfa score, MEWS score, MEDS score, etc.

End point indicator and follow-up:

1) the main endpoint indexes are: mortality in 28 days;

2) secondary endpoint indicator: 7 days of fatality rate; (ii) Mechanical Ventilation ratio (MV); (iii) entering ICU proportion (AICU);

3) follow-up: the admitted patient adopts a his system and ward follow-up to observe the destination index of the patient, and the discharged patient adopts telephone follow-up or clinic follow-up; patients with hospitalization less than 28 days of survival discharge or 28 days of follow-up survival are considered "alive".

Note: in the present invention, an event corresponding to the end point indicator is referred to as an "end point event".

Experimental example 1 ability of the present invention to evaluate prognosis of low, medium and high risk sepsis patients

1. Method of producing a composite material

Subjects were scored using the prognostic evaluation system of the present invention and classified into low-risk groups (PPS: 0 to 6 points, n-79), medium-risk groups (PPS: 7 to 9 points, n-79), and high-risk groups (PPS: 10 points and above, n-78).

And (4) counting the 28-day mortality, 7-day mortality, 28-day mechanical ventilation rate and 28-day survival ICU rate of the low-risk group and the medium-risk combined high-risk group.

2. Results

The 28-day fatality rates of low-risk, medium-risk and high-risk sepsis patients are respectively 3.8%, 13.9% and 43.6%, and the difference has statistical significance (P is less than 0.001); the 7-day fatality rates of low-risk, medium-risk and high-risk sepsis patients are respectively 1.3%, 6.3% and 26.9%, and the difference has statistical significance (P is less than 0.001); the mechanical ventilation rates of 28 days of low-risk, medium-risk and high-risk sepsis patients are respectively 25.3%, 29.1% and 67.9%, and the difference has statistical significance (P is less than 0.001); the ICU rates of 28-day survival of low-risk, medium-risk and high-risk sepsis patients are 22.8%, 32.9% and 60.3%, and the difference has statistical significance (P is less than 0.001).

Experimental example 2 evaluation rule of evaluation of PPS Performance of the present invention

1. Method of producing a composite material

1.1 precision:

and comparing the expected frequency of PPS score with the observation frequency of distribution by adopting goodness-of-fit inspection, and judging whether the two frequencies have obvious difference.

The basic idea of goodness of fit test here is as follows:

1) root of the subjectGrouping according to PPS score, and sorting the groups from small to large according to PPS score into 10Small Group of；

2) Calculating expected frequency and observation frequency in each group respectively, wherein the expected frequency is the frequency of each group in the test groupGroup ofSumming the frequency counts of the internally occurring end-point events, wherein the observation frequency count is the sum of the frequency counts of the internally occurring end-point events in each subgroup in the verification group;

3) and calculating chi-square values according to the expected frequency and the observed frequency of each group, and obtaining P values according to chi-square distribution.

If the obtained chi-square value is smaller, the corresponding P value is larger, and the prediction accuracy is better.

1.2, degree of distinction:

A. area under subject's working curve (AUC)

Plotting and comparing the PPS score to the AUC of APACHE II, SOFA, qSOFA, MEWS, MEDS compares the ability of PPS and other traditional scores to predict the accuracy of 28-day sepsis mortality.

The larger the AUC, the better the discrimination of the prediction model. Generally speaking, AUC < 0.6 means poor discrimination, 0.6-0.75 means that the model has certain discrimination capability, and >0.75 means good discrimination capability.

B. Novel reclassification analysis method

Currently, it is internationally recommended to use a novel Reclassification Analysis method to evaluate the Discrimination of risk score model, so we use Net Reclassification Improvement (NRI), Integrated Differentiation Improvement (IDI), Decision Curve Analysis (DCA) to evaluate the capability of PPS to predict the Discrimination of 28-day sepsis fatality rate.

2. Results

2.1 precision of PPS prediction for 28-day mortality of sepsis

The result of the goodness-of-fit test (HL test) shows that the P value of the PPS in predicting 28-day mortality of sepsis is 0.669, which prompts that the PPS model has stronger disease prognosis prediction capability, and the HL test chart shows that the expected frequency and the observation frequency have no significant difference. See fig. 1.

2.2 comparison of the accuracy of the prediction of sepsis prognosis of PPS with other sepsis scores

1) Death rate in 28 days

The area under the curve (AUC) for 28-day mortality assessed by PPS was 0.762 (95% CI 0.702-0.815, P < 0.001), equal to SOFA (AUC 0.762), higher than MEWS (AUC 0.656), with statistical significance (P < 0.05); slightly higher than APACHE II (AUC 0.761), higher than MEDS (AUC 0.724) and qSOFA (AUC 0.695), but the differences were not statistically significant (P > 0.05) (see table 1).

TABLE 1 comparison of PPS to other sepsis scores to predict sepsis prognostic efficacy

Note: PPS: pre-hospital prognosis prediction score, apache ii: acute physiological and chronic health status scoring system, SOFA: sequential organ failure score, MEDS: emergency department sepsis related mortality score, mems: improved early warning score, qSOFA: rapid sequential organ failure scoring.

2)7 days mortality

The area under the curve (AUC) for PPS assessed 7-day mortality was 0.777 (95% CI 0.719-0.829, P < 0.001), slightly lower than APACHE II (AUC 0.788), higher than SOFA (AUC 0.762), med (AUC 0.707), MEWS (AUC 0.721) and qSOFA (AUC 0.772), but the differences were not statistically significant (P > 0.05) (see table 2).

3)28 days mechanical ventilation

The AUC for 28 days mechanical ventilation evaluated by PPS was 0.718 (95% CI 0.656-0.774, P < 0.001), lower than SOFA (AUC 0.873), higher than APACHE II (AUC 0.698), med (AUC 0.688), MEWS (AUC 0.640) and qSOFA (AUC 0.697), with statistical significance for differences compared to SOFA and MEWS (P < 0.05) (see table 2).

4) ICU Rate of 28 days stay

The AUC for PPS assessed 28-day occupancy in ICU was 0.701 (95% CI0.638-0.759, P < 0.001), lower than SOFA (AUC 0.817), higher than APACHE II (AUC 0.684), MEDS (AUC 0.672), MEWS (AUC 0.663) and qSOFA (AUC 0.693), but the differences were not statistically significant (P > 0.05) (see table 2).

TABLE 2 comparison of PPS with other sepsis scores to predict sepsis prognostic efficacy

2.3 comparison of PPS with SOFA and APACHE II in predicting mortality discrimination at 28 days of sepsis

Since the area under the curve (AUC) for PPS and SOFA predicting 28-day mortality from sepsis is the largest and the same, the inventors compared the ability of these two scores to predict the discrimination of 28-day mortality from sepsis using the net reclassification method (NRI), Integrated Discriminatory Improvement (IDI), and Decision Curve Analysis (DCA).

1) Net Reclassification Improvement (NRI) and Integrated Difference Improvement (IDI)

In the death group, PPS was less divided by 6(8vs.14) patients than SOFA into the mid-high risk group, resulting in an upregulation of risk assessment (NRI +) of-0.125; in the survival group, PPS divided 7(46vs.39) more patients than SOFA into the low-intermediate risk group, resulting in a risk assessment downregulation (NRI-) of 0.037. Thus, PPS predicts 28-day mortality from sepsis as compared to SOFA with a total NRI of-0.088, P0.42; the Integration Discrimination Improvement (IDI) was-0.039, P ═ 0.27 (see table 3).

Compared to SOFA, there was no statistical difference between NRI and IDI (P > 0.05) in PPS, indicating no significant difference between PPS and SOFA in the ability to stratify low, high, and high risk patients.

TABLE 3 Net reclassification Table for validation group PPS score and SOFA score prediction 28-day mortality

2) Decision Curve Analysis (DCA)

As shown in fig. 2, Treat None indicated that all samples were negative, all were untreated, and the net benefit was 0; treat All represents the net benefit curve for the case where All samples were positive and All were treated. The decision analysis curve results show that the Net benefit of PPS in predicting mortality at 28 days of sepsis (Net belit) is better than either SOFA or APACHE II at any Threshold Probability (Threshold Probability) (see fig. 2).

In conclusion, the net benefit of PPS in predicting 28-day mortality from sepsis is better than that of SOFA or APACHE II, indicating that the prognosis evaluation system of the invention has higher discrimination on 28-day mortality from sepsis.

EXAMPLE 3 subgroup analysis of PPS for predicting 28-day mortality from sepsis

1. Method of producing a composite material

Patients were grouped by sex, age, white blood cells, platelets, lactate, SOFA, APACHE II, state of consciousness, mechanical ventilation and whether vasoactive drugs were used and the effect of PPS on sepsis 28-day death was analyzed using Logistic regression.

2. Results

The results show that: PPS is independently associated with 28-day mortality from sepsis in subgroups of different sex, age, leukocytes, platelets, lactate, SOFA, APACHE II, state of consciousness, mechanical ventilation, use of vasoactive drugs, etc. (see table 4).

TABLE 4 subgroup analysis of PPS and 28-day mortality from sepsis

In conclusion, the sepsis prognosis evaluation system can well distinguish low, medium and high risk sepsis patients and can guide risk stratification; the invention has high diagnosis accuracy which is not inferior to SOFA and APACHE II, and the discrimination of prognosis evaluation is superior to the two; the PPS score can also be independently related to 28-day mortality of sepsis in subgroups of different sexes, ages, leukocyte numbers, platelet numbers, lactic acid concentrations, SOFA scores, APACHE II scores, consciousness states, mechanical ventilation, use of vascular drugs and the like, and can be applied to prognosis prediction of sepsis in each subgroup.

Claims

1. A sepsis prognosis evaluation system is characterized by comprising an input module, a scoring module, a diagnosis module and an output module;

the scoring module receives information from the input module and scores according to the following rules:

4) disturbance of consciousness: judging the consciousness disturbance if the Glassge coma score is less than or equal to 14 points; if the consciousness is disturbed, 7 points are counted; if the patient is unconscious, the score is 0;

5) summing the four fractions to obtain a total fraction;

(1) when the total score is 0-6, the diagnosis is concluded as: low risk;

the output module is responsible for outputting the diagnosis conclusion.

2. The evaluation system of claim 1, wherein the output module further outputs the total score and/or the scores of the individual items obtained by the scoring module.

3. The assessment system of claim 1, wherein the disturbance of consciousness is: lethargy, coma, shallow coma, moderate coma or deep coma.