Use of sepsis-related diagnostic criteria in primary care: a survey among general practitioners.

BACKGROUND: Use of sepsis-criteria in hospital settings is effective in realizing early recognition, adequate treatment and reduction of sepsis-associated morbidity and mortality. Whether general practitioners (GPs) use these diagnostic criteria is unknown. OBJECTIVE: To gauge the knowledge and use of various diagnostic criteria. To determine which parameters GPs associate with an increased likelihood of sepsis. METHODS: Two thousand five hundred and sixty GPs were invited and 229 agreed to participate in a survey, reached out to through e-mail and WhatsApp groups. The survey consisted of two parts: the first part aimed to obtain information about the GP, training and knowledge about sepsis recognition, and the second part tested specific knowledge using six realistic cases. RESULTS: Two hundred and six questionnaires, representing a response rate of 8.1%, were eligible for analysis. Gut feeling (98.1%) was the most used diagnostic method, while systemic inflammatory response syndrome (37.9%), quick Sequential Organ Failure Assessment (qSOFA) (7.8%) and UK Sepsis Trust criteria (UKSTc) (1.5%) were used by the minority of the GPs. Few of the responding GPs had heard of either the qSOFA (27.7%) or the UKSTc (11.7%). Recognition of sepsis varied greatly between GPs. GPs most strongly associated the individual signs of the qSOFA (mental status, systolic blood pressure, capillary refill time and respiratory rate) with diagnosing sepsis in the test cases. CONCLUSIONS: GPs mostly use gut feeling to diagnose sepsis and are frequently not familiar with the 'sepsis-criteria' used in hospital settings, although clinical reasoning was mostly in line with the qSOFA score. In order to improve sepsis recognition in primary care, GPs should be educated in the use of available screening tools.

Ambulance dispatch versus general practitioner home visit for highly urgent out-of-hours primary care.

Background: Patients with life-threatening conditions who contact out-of-hours primary care either receive a home visit from a GP of a GP cooperative (GPC) or are handed over to the ambulance service. Objective: The objective of this study was to determine whether highly urgent visits, after a call to the GPC, are delivered by the most appropriate healthcare provider: GPC or ambulance service. Methods: We performed a cross-sectional study using patient record data from a GPC and ambulance service in an urban district in The Netherlands. During a 21-month period, all calls triaged as life-threatening (U1) to the GPCs were included. The decision to send an ambulance or not was made by the triage nurse following a protocolized triage process. Retrospectively, the most appropriate care was judged by the patient's own GP, using a questionnaire. Results: Patient and care characteristics from 1081 patients were gathered: 401 GPC visits, 570 ambulance responses and 110 with both ambulance and GPC deployment. In 598 of 1081 (55.3%) cases, questionnaires were returned by the patients' own GP. About 40% of all visits could have been carried out with a lower urgency in retrospect, and almost half of all visits should have received a different type of care or different provider. In case of ambulance response, 60.7% concerned chest pain. Conclusion: Research should be done on the process of triage and allocation of care to optimize labelling complaints with the appropriate urgency and to deploy the appropriate healthcare provider, especially for patients with chest pain.

Potential impact of a new sepsis prediction model for the primary care setting: early health economic evaluation using an observational cohort.

OBJECTIVES: To estimate the potential referral rate and cost impact at different cut-off points of a recently developed sepsis prediction model for general practitioners (GPs). DESIGN: Prospective observational study with decision tree modelling. SETTING: Four out-of-hours GP services in the Netherlands. PARTICIPANTS: 357 acutely ill adult patients assessed during home visits. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is the cost per patient from a healthcare perspective in four scenarios based on different cut-off points for referral of the sepsis prediction model. Second, the number of hospital referrals for the different scenarios is estimated. The potential impact of referral of patients with sepsis on mortality and hospital admission was estimated by an expert panel. Using these study data, a decision tree with a time horizon of 1 month was built to estimate the referral rate and cost impact in case the model would be implemented. RESULTS: Referral rates at a low cut-off (score 2 or 3 on a scale from 0 to 6) of the prediction model were higher than observed for patients with sepsis (99% and 91%, respectively, compared with 88% observed). However, referral was also substantially higher for patients who did not need hospital assessment. As a consequence, cost-savings due to referral of patients with sepsis were offset by increased costs due to unnecessary referral for all cut-offs of the prediction model. CONCLUSIONS: Guidance for referral of adult patients with suspected sepsis in the primary care setting using any cut-off point of the sepsis prediction model is not likely to save costs. The model should only be incorporated in sepsis guidelines for GPs if improvement of care can be demonstrated in an implementation study. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NTR 7026).

Predicting sepsis-related mortality and ICU admissions from telephone triage information of patients presenting to out-of-hours GP cooperatives with acute infections: A cohort study of linked routine care databases.

BACKGROUND: General practitioners (GPs) often assess patients with acute infections. It is challenging for GPs to recognize patients needing immediate hospital referral for sepsis while avoiding unnecessary referrals. This study aimed to predict adverse sepsis-related outcomes from telephone triage information of patients presenting to out-of-hours GP cooperatives. METHODS: A retrospective cohort study using linked routine care databases from out-of-hours GP cooperatives, general practices, hospitals and mortality registration. We included adult patients with complaints possibly related to an acute infection, who were assessed (clinic consultation or home visit) by a GP from a GP cooperative between 2017-2019. We used telephone triage information to derive a risk prediction model for sepsis-related adverse outcome (infection-related ICU admission within seven days or infection-related death within 30 days) using logistic regression, random forest, and neural network machine learning techniques. Data from 2017 and 2018 were used for derivation and from 2019 for validation. RESULTS: We included 155,486 patients (median age of 51 years; 59% females) in the analyses. The strongest predictors for sepsis-related adverse outcome were age, type of contact (home visit or clinic consultation), patients considered ABCD unstable during triage, and the entry complaints"general malaise", "shortness of breath" and "fever". The multivariable logistic regression model resulted in a C-statistic of 0.89 (95% CI 0.88-0.90) with good calibration. Machine learning models performed similarly to the logistic regression model. A "sepsis alert" based on a predicted probability >1% resulted in a sensitivity of 82% and a positive predictive value of 4.5%. However, most events occurred in patients receiving home visits, and model performance was substantially worse in this subgroup (C-statistic 0.70). CONCLUSION: Several patient characteristics identified during telephone triage of patients presenting to out-of-hours GP cooperatives were associated with sepsis-related adverse outcomes. Still, on a patient level, predictions were not sufficiently accurate for clinical purposes.

Added Diagnostic Value of Biomarkers in Patients with Suspected Sepsis: A Prospective Cohort Study in Out-Of-Hours Primary Care.

BACKGROUND: Point-of-care testing (POCT) has shown promising results in the primary care setting to improve antibiotic therapy in respiratory tract infections and it might also aid general practitioners (GPs) to decide if patients should be referred to a hospital in cases of suspected sepsis. We aimed to assess whether biomarkers with possible POCT use can improve the recognition of sepsis in adults in the primary care setting. METHODS: We prospectively included adult patients with suspected severe infections during out-of-hours home visits. Relevant clinical signs and symptoms were recorded, as well as the biomarkers C-reactive protein, lactate, procalcitonin, high-sensitive troponin I, N-terminal pro b-type natriuretic peptide, creatinine, urea, and pancreatic stone protein. We used a POCT device for lactate only, and the remaining biomarkers were measured in a laboratory from stored blood samples. The primary outcome was sepsis within 72 h of inclusion. The potential of biomarkers to either rule in or rule out sepsis was tested for individual biomarkers combined with a model consisting of signs and symptoms. Net reclassification indices were also calculated. RESULTS: In total, 336 patients, with a median age of 80 years, were included. One hundred forty-one patients (42%) were diagnosed with sepsis. The C statistic for the model with clinical symptoms and signs was 0.84 (95% CI 0.79-0.88). Both lactate and procalcitonin increased the C statistic to 0.85, but none of the biomarkers significantly changed the net reclassification index. CONCLUSIONS: We do not advocate the routine use of POCT in general practice for any of the tested biomarkers of suspected sepsis.

The accuracy and feasibility of respiratory rate measurements in acutely ill adult patients by GPs: a mixed-methods study.

BACKGROUND: Tachypnoea in acutely ill patients can be an early sign of a life-threatening condition such as sepsis. Routine measurement of the respiratory rate by GPs might improve the recognition of sepsis. AIM: To assess the accuracy and feasibility of respiratory rate measurements by GPs. DESIGN & SETTING: Observational cross-sectional mixed-methods study in the setting of out-of-hours (OOH) home visits at three GP cooperatives in The Netherlands. METHOD: GPs were observed during the assessment of acutely ill patients, and semi-structured interviews were performed. The GP-assessed respiratory rate was compared with a reference measurement. In the event that the respiratory rate was not counted, GPs were asked to estimate the rate (dichotomised as ≥22 breaths per minute or <22 breaths per minute). RESULTS: Observations of 130 acutely ill patients were included, and 14 GPs were interviewed. In 33 patients (25%), the GP counted the respiratory rate. A mean difference of 0.27 breaths per minute (95% confidence interval [CI] = -5.7 to 6.3) with the reference measurement was found. At a cut-off point of ≥22 breaths per minute, a sensitivity of 86% (95% CI = 57% to 98%) was found when the GP counted the rate, and a sensitivity of 43% (95% CI = 22% to 66%) when GPs estimated respiratory rates. GPs reported both medical and practical reasons for not routinely measuring the respiratory rate. CONCLUSION: GPs are aware of the importance of assessing the respiratory rate of acutely ill adult patients, and counted measurements are accurate. However, in most patients the respiratory rate was not counted, and the rate was often underestimated when estimated.

New clinical prediction model for early recognition of sepsis in adult primary care patients: a prospective diagnostic cohort study of development and external validation.

BACKGROUND: Recognising patients who need immediate hospital treatment for sepsis while simultaneously limiting unnecessary referrals is challenging for GPs. AIM: To develop and validate a sepsis prediction model for adult patients in primary care. DESIGN AND SETTING: This was a prospective cohort study in four out-of-hours primary care services in the Netherlands, conducted between June 2018 and March 2020. METHOD: Adult patients who were acutely ill and received home visits were included. A total of nine clinical variables were selected as candidate predictors, next to the biomarkers C-reactive protein, procalcitonin, and lactate. The primary endpoint was sepsis within 72 hours of inclusion, as established by an expert panel. Multivariable logistic regression with backwards selection was used to design an optimal model with continuous clinical variables. The added value of the biomarkers was evaluated. Subsequently, a simple model using single cut-off points of continuous variables was developed and externally validated in two emergency department populations. RESULTS: A total of 357 patients were included with a median age of 80 years (interquartile range 71-86), of which 151 (42%) were diagnosed with sepsis. A model based on a simple count of one point for each of six variables (aged >65 years; temperature >38°C; systolic blood pressure ≤110 mmHg; heart rate >110/min; saturation ≤95%; and altered mental status) had good discrimination and calibration (C-statistic of 0.80 [95% confidence interval = 0.75 to 0.84]; Brier score 0.175). Biomarkers did not improve the performance of the model and were therefore not included. The model was robust during external validation. CONCLUSION: Based on this study's GP out-of-hours population, a simple model can accurately predict sepsis in acutely ill adult patients using readily available clinical parameters.

Vital signs of the systemic inflammatory response syndrome in adult patients with acute infections presenting in out-of-hours primary care: A cross-sectional study.

BACKGROUND: Signs of the systemic inflammatory response syndrome (SIRS) - fever (or hypothermia), tachycardia and tachypnoea - are used in the hospital setting to identify patients with possible sepsis. OBJECTIVES: To determine how frequently abnormalities in the vital signs of SIRS are present in adult out-of-hours (OOH) primary care patients with suspected infections and assess the association with acute hospital referral. METHODS: We conducted a cross-sectional study at the OOH GP cooperative in Nijmegen, the Netherlands, between August and October 2015. GPs were instructed to record the body temperature, heart rate and respiratory rate of all patients with suspected acute infections. Vital signs of SIRS, other relevant signs and symptoms, and referral state were extracted from the electronic registration system of the OOH GP cooperative retrospectively. Logistic regression analysis was used to evaluate the association between clinical signs and hospital referral. RESULTS: A total of 558 patients with suspected infections were included. At least two SIRS vital signs were abnormal in 35/409 (8.6%) of the clinic consultations and 60/149 (40.3%) of the home visits. Referral rate increased from 13% when no SIRS vital sign was abnormal to 68% when all three SIRS vital signs were abnormal. Independent associations for referral were found for decreased oxygen saturation, hypotension and rapid illness progression, but not for individual SIRS vital signs. CONCLUSION: Although patients with abnormal vital signs of SIRS were referred more often, decreased oxygen saturation, hypotension and rapid illness progression seem to be most important for GPs to guide further management.

Development of a clinical prediction rule for sepsis in primary care: protocol for the TeSD-IT study.

BACKGROUND: Early recognition and treatment of sepsis is crucial to prevent detrimental outcomes. General practitioners (GPs) are often the first healthcare providers to encounter seriously ill patients. The aim of this study is to assess the value of clinical information and additional tests to develop a clinical prediction rule to support early diagnosis and management of sepsis by GPs. METHODS: We will perform a diagnostic study in the setting of out-of-hours home visits in four GP cooperatives in the Netherlands. Acutely ill adult patients suspected of a serious infection will be screened for eligibility by the GP. The following candidate predictors will be prospectively recorded: (1) age, (2) body temperature, (3) systolic blood pressure, (4) heart rate, (5) respiratory rate, (6) peripheral oxygen saturation, (7) mental status, (8) history of rigors, and (9) rate of progression. After clinical assessment by the GP, blood samples will be collected in all patients to measure C-reactive protein, lactate, and procalcitonin. All patients will receive care as usual. The primary outcome is the presence or absence of sepsis within 72 h after inclusion, according to an expert panel. The need for hospital treatment for any indication will be assessed by the expert panel as a secondary outcome. Multivariable logistic regression will be used to design an optimal prediction model first and subsequently derive a simplified clinical prediction rule that enhances feasibility of using the model in daily clinical practice. Bootstrapping will be performed for internal validation of both the optimal model and simplified prediction rule. Performance of both models will be compared to existing clinical prediction rules for sepsis. DISCUSSION: This study will enable us to develop a clinical prediction rule for the recognition of sepsis in a high-risk primary care setting to aid in the decision which patients have to be immediately referred to a hospital and who can be safely treated at home. As clinical signs and blood samples will be obtained prospectively, near-complete data will be available for analyses. External validation will be needed before implementation in routine care and to determine in which pre-hospital settings care can be improved using the prediction rule. TRIAL REGISTRATION: The study is registered in the Netherlands Trial Registry (registration number NTR7026).

[Early recognition of sepsis; a diagnostic challenge for the general practitioner]. / Vroege herkenning van sepsis.

Early recognition and treatment of sepsis is essential to prevent morbidity and mortality. Many sepsis patients are initially assessed by a general practitioner (GP). Delay can be prevented if patients are referred to the hospital as soon as possible. However, signs and symptoms of sepsis can be subtle or aspecific, complicating the distinction between patients who need urgent care and patients who can be safely treated at home. We describe three patients who were admitted to the intensive care after repeated assessment by GPs in an out-of-hours setting: a 76-year-old man who was diagnosed with urosepsis, an 86-year-old man who was diagnosed with pneumosepsis and a 49-year-old man who was admitted after cardiopulmonary resuscitation due to sepsis. In all cases risk factors and signs of sepsis were present, but the sepsis had not been recognized until presentation to the hospital.

Management of sepsis in out-of-hours primary care: a retrospective study of patients admitted to the intensive care unit.

OBJECTIVES: Timely recognition and treatment of sepsis is essential to reduce mortality and morbidity. Acutely ill patients often consult a general practitioner (GP) as the first healthcare provider. During out-of-hours, GP cooperatives deliver this care in the Netherlands. The aim of this study is to explore the role of these GP cooperatives in the care for patients with sepsis. DESIGN: Retrospective study of patient records from both the hospital and the GP cooperative. SETTING: An intensive care unit (ICU) of a general hospital in the Netherlands, and the colocated GP cooperative serving 260 000 inhabitants. PARTICIPANTS: We used data from 263 patients who were admitted to the ICU due to community-acquired sepsis between January 2011 and December 2015. MAIN OUTCOME MEASURES: Contact with the GP cooperative within 72 hours prior to hospital admission, type of contact, delay from the contact until hospital arrival, GP diagnosis, initial vital signs and laboratory values, and hospital mortality. RESULTS: Of 263 patients admitted to the ICU, 127 (48.3%) had prior GP cooperative contacts. These contacts concerned home visits (59.1%), clinic consultations (18.1%), direct ambulance deployment (12.6%) or telephone advice (10.2%). Patients assessed by a GP were referred in 64% after the first contact. The median delay to hospital arrival was 1.7 hours. The GP had not suspected an infection in 43% of the patients. In this group, the in-hospital mortality rate was significantly higher compared with patients with suspected infections (41.9% vs 17.6%). Mortality difference remained significant after correction for confounders. CONCLUSION: GP cooperatives play an important role in prehospital management of sepsis and recognition of sepsis in this setting proved difficult. Efforts to improve management of sepsis in out-of-hours primary care should not be limited to patients with a suspected infection, but also include severely ill patients without clear signs of infection.

Recognition of sepsis in primary care: a survey among GPs.

BACKGROUND: Early recognition and treatment of sepsis are important to reduce morbidity and mortality. Screening tools using vital signs are effective in emergency departments. It is not known how the decision to refer a patient to the hospital with a possible serious infection is made in primary care. AIM: To gain insight into the clinical decision-making process of GPs in patients with possible sepsis infections. DESIGN & SETTING: Survey among a random sample of 800 GPs in the Netherlands. METHOD: Quantitative questionnaire using Likert scales. RESULTS: One hundred and sixty (20.3%) of questionnaires were eligible for analysis. Based on self-reported cases of possible serious infections, the factors most often indicated as important for the decision to refer patients to the hospital were: general appearance (94.1%), gut feeling (92.1%), history (92.0%), and physical examination (89.3%). Temperature (88.7%), heart rate (88.7%), and blood pressure (82.1%), were the most frequently measured vital signs. In general, GPs more likely referred patients in case of: altered mental status (98.7%), systolic blood pressure <100 mmHg (93.7%), unable to stand (89.3%), insufficient effect of previous antibiotic treatment (87.4%), and respiratory rate ≥22/minute (86.1%). CONCLUSION: The GPs' assessment of patients with possible serious infection is a complex process, in which besides checking vital signs, many other aspects of the consultation guide the decision to refer a patient to the hospital. To improve care for patients with sepsis, the diagnostic and prognostic value of assessing the vital signs and symptoms, GPs' gut feeling, and additional diagnostic tests, should be prospectively studied in the primary care setting.