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Although sepsis is well recognised as a medical emergency, it can be difficult to identify given its various clinical presentations. Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. These are also key components in international guidelines for managing sepsis.1–3

A set of guidelines for sepsis known as the Sepsis Pathway (Figure 1) was included in a pre-formed pack of equipment and introduced in three emergency departments—Monash Medical Centre (tertiary hospital), Dandenong Hospital and Casey Hospital (district hospitals) in June 2015. This aimed to promote early recognition and response to patients with potential sepsis. It details steps to assist clinicians to: i) recognise, ii) respond and escalate, iii) resuscitate and reassess, and iv) refer septic patients. After ethics approval the first Victorian sepsis pathway was developed by the Monash health multidisciplinary sepsis group. Monash Health is the largest health network in the state of Victoria, Australia, with an annual emergency department network census of about 200,000 presentations. It comprises of three hospitals: Monash Medical Centre (tertiary referral), Dandenong and Casey hospitals (district hospitals).

Figure 1: Sepsis flowchart checklist.

To assist with the recognition of sepsis, the guideline includes a checklist of vital sign parameters, which vary slightly from the well-known Systemic Inflammatory Response Criteria, but are aligned with Australian Observation and Response Charts.4 The Guideline suggests responding to patients with two or more observations that fall within the set criteria with a review by a senior clinician within 30 minutes.

The pathway advises collection of blood for multiple tests including two sets of blood cultures, a venous blood gas and a lactate level. However, it also emphasises that administration of empirical antibiotics for sepsis should not be delayed by investigations or results (Figure 2).

Figure 2: Sepsis management plan.

The Sepsis Pathway was introduced as part of a Sepsis Pack, designed to support clinicians in performing the steps outlined in the guideline. The Sepsis Pack includes equipment for intravenous cannulation and intravenous fluids, as well as for collection of blood for culture and lactate measurement.

This article evaluates the impact of the implementation of the Sepsis Pathway Programme on the recognition, early investigation and management of septic patients in the emergency department.

Methods

The aim of this pathway was to improve recognition of patients with sepsis (RECOGNISE) and to initiate early management with intravenous fluid and antimicrobial therapy (REACT). The Sepsis Pathway was designed with broad inclusion criteria to identify sepsis as well as risk stratify potential septic patients. There are a set of risk factors based on history and physical examination to identify high-risk patients:

• Immunocompromised/chronic illness/chemotherapy/radiotherapy

• Abdominal pain/distension/peritonism

• Indwelling medical device

• Cough/sputum/breathlessness

• Recent surgery/invasive procedure

• New onset of confusion/altered LOC/neck stiffness/headache

• History of fever or rigors

• Re-presentation within 48 hours

• Wound infection/cellulitis

• Fall not related to mechanism of injury

• Dysuria/frequency/odour

• Age >65yo

This, in conjunction with the analysis of the patients’ vital signs can be used to risk stratify patients. Vital signs triggering the initiation of Sepsis Pathway are as follows:

• Respirations ≤10 or ≥25 per minute

• SpO2 ≤95%

• Systolic blood pressure ≤100mmHg

• Heart rate ≤50 or ≥120 per minute

• Altered LOC or new onset of confusion

• Temp <35.5 °C or >38.5 °C

High-risk patients are identified if:

• Lactate ≥4mmol/L

• Immunocompromised

• SBP ≤90mmHg

• Base excess <-5.0

After identification of a septic or potentially septic patient, the pathway is strictly followed.

An explicit Sepsis Data Collection Form to assess the effect of the Sepsis Pathway was added to Sepsis Packs at Casey Hospital, a district hospital with mixed emergency department (adults and paediatrics) with about 60,000 presentations annually. A comparative prospective cohort study of patients presenting with suspected sepsis pre- and post-implementation of the Sepsis Pathway was then conducted. This was in conjunction with multidisciplinary Monash Health sepsis pathway development programme, which was approved by the ethics committee. From June to December 2015, data was collected prospectively for patients who were identified in the emergency department to have potential sepsis. The outcomes were measured for groups where the Sepsis Pathway was used and not used. Cases where a diagnosis of sepsis was missed in the emergency department were identified through a search of electronic medical records (EMR) looking for all patients subsequently diagnosed with sepsis as well as those that had documented positive blood cultures during admission. Those with growth on blood culture of a gram-positive cocci were excluded from this group as they were considered false positives due to likely contamination.

These groups were compared to a control group which included patients with suspected sepsis who presented to the same emergency department from June to December 2014, a year prior to the implementation of the Sepsis Pathway. These patients were identified through a search of EMR looking for patients who were diagnosed with sepsis in the emergency department. Those cases that were missed in the emergency department were also included. They were identified through a search of the EMR looking for patients diagnosed with sepsis throughout their admission or those had positive blood cultures during admission. Similar to above, false positives were duly accounted for and excluded as any growth of gram-positive cocci were considered most likely contaminated samples. We compared the control group (2014) to the group of patients specifically placed on the Sepsis Pathway (2015), as well as those that were missed and later identified through EMR during the intervention period. Patients <18 years old, those who were already taking a course of antibiotics as an outpatient prior to their presentation and those that were transferred to other hospitals during admission were excluded from the study.

The following data was collected:

• Date of birth

• Triage time and date

• Triage category

• Presenting problem at triage

• Time to antibiotic from time of triage

• Time to lactate measurement from time of triage

• Number of cases where blood cultures were taken

• Number of intensive care admissions

• Length of intensive care admission

• Length of hospital admission

• In-hospital mortality

Analysis included the calculation of odds ratios with 95% confidence intervals according to Altman and p-values using Fisher’s exact and t test. Statistical significance was defined as p<0.05.

Results

Following the introduction of the Sepsis Pathway, a total of 109 patients were identified to be septic, either at presentation in the emergency department or throughout admission during the study period of 15 June to 31 December 2015. Of these, 52 cases were identified prospectively to be septic through the initiation and completion of the Sepsis Pathway Collection Form. This group will be referred to as the ‘Sepsis Pathway’ Group. It also includes patients who were identified and treated as septic, and subsequently transferred to intensive care unit from the emergency department. The remaining cases were either those identified with sepsis in the emergency department but were not treated with the Sepsis Pathway or those that were missed and identified to be septic throughout their admission. These groups were identified to have sepsis through a retrospective search of the EMR using positive blood cultures collected on presentation or during their admission. The missed cases that had gram-positive cocci grown on blood culture were excluded as they were presumed to be contaminated samples and could bias the data. This group will be referred to as the ‘Missed Cases Group’. The pre-intervention control group included 139 patients who presented from 15 June to 31 December 2014. They were either identified in the emergency department to be septic, were documented as septic during their admission or had a true positive blood culture, again excluding any cases that could be contaminated (gram positive cocci growth on blood culture).

Figure 3: Breakdown of the septic patients for both the control and intervention group.

The Pre-intervention Control Group (2014) had a median age of 78 (IQR 56–91). Patients in the ‘Sepsis Pathway Group (2015)’ and the ‘Missed Cases Group (2015)’ had a median age of 67 (IQR 53.75–81) and 69 (IQR 50–84), respectively.

In the study period prior to the implementation of the Sepsis Pathway, there was a significantly lower proportion of septic patients who were triaged as Category 1 according to the Australasian Triage Scale (ATS) from no cases in the pre-intervention period to three cases in the Sepsis Pathway Group (0% vs 5.8%, p=0.0193).5

Figure 4: Comparison of the triage categories.

The three most common presenting problems in all groups were ‘febrile/PUO’ (17.8% of all cases), ‘shortness of breath’ (13.9% of all cases) and ‘generally unwell’ (15.4% of all cases).

Table 1: The three most common presenting problems.

The median time to antibiotic administration in the Sepsis Pathway Group improved significantly compared to the Control Group (75 minutes vs 182 minutes, p<0.00001). The proportion of patients who received antibiotics within 60 minutes of triage was greater in the Sepsis Pathway Group than in the pre-intervention group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69–13.81, p<0.0001).

Figure 5: Antibiotics administered within the hour.

Similarly, the median time to lactate measurement was significantly shorter in the Sepsis Pathway Group compared to the pre-intervention group (54.5 minutes vs. 64 minutes, p=0.0117). A greater proportion of patients had their lactate measured within 60 minutes of triage in the Sepsis Pathway Group than in the pre-intervention group and this was statistically significant (53.8% vs 27.3%, OR 2.86, 95% CI 1.49–5.49, p=0.0016).

Figure 6: Lactate measured within the hour.

Table 2: Median time to antibiotics administration and lactate measurement.

Serum lactate levels were tested more often in the Sepsis Pathway Group than in the Control Group (92.3% vs 64.0%, OR 6.74, 95% CI 2.30–19.80, p=0.0005). Blood cultures were sent in all of the cases that utilised the Sepsis Pathway; 20.9% of the cases in the pre-implementation group did not have blood cultures taken during their admission.

Table 3: Number of blood culture and lactate done in each group.

There was an increase in the rate of ICU admission in the Sepsis Pathway group when compared to the pre-intervention group; however, this was not statistically significant (28.8% vs 16.5%, OR 1.94, 95% CI 0.92–4.09, p=0.0823).

No significant differences were seen between the groups when looking at the median length of stay in ICU, length of hospital admission or mortality.

Table 4: ICU admission rates and length of stay, hospital length of stay and mortality comparison.

Discussion

Recognition of sepsis and the importance of prompt management appear to have improved following the introduction of the Sepsis Pathway Flowchart. This is demonstrated by the reduction of missed cases in the emergency department following the implementation of the Sepsis Pathway when compared to the pre-implementation phase (69.1% vs 20.5%). This decrease could be due to the guideline being presented as a checklist to medical staff, allowing doctors to follow it easily even when they are unsure. Though there is a decrease in the number of missed cases after the implementation of the Sepsis Pathway, there is still room for improvement. False negatives remain with non-specific presentations or early presenting features not covered by the checklist. Additionally, in 2015, more patients were triaged as Category 1 and 2 compared to prior to the implementation of the Sepsis Pathway (38.5% vs 22.3%). Being classified in a more urgent Triage Category, these patients are more likely to be seen by a clinician earlier and subsequently, investigation and management may be initiated earlier. Previous sepsis quality improvement programmes have also resulted in increases in the number of patients in higher urgency triage categories, such as ATS 1 or 2, and there were also reciprocal reductions in less urgent triage categories.5

In sepsis, delay in administration of appropriate antibiotics is associated with increased mortality. Commencing appropriate antibiotic therapy as soon as possible in septic patients is ideal, with international guidelines recommending one hour as a reasonable minimal target.3,7 The median time to antibiotic administration was shorter in the Sepsis Pathway Group with significantly more patients receiving antibiotics within 60 minutes of being triaged. However, the median time remained suboptimal even after the introduction of the Sepsis Pathway with 64.5% of antibiotic administration times exceeding the target of 60 minutes.

There has been a recent change in the classification of sepsis, with the introduction of the sepsis 3 criteria. Lactate levels are included in the clinical criteria for septic shock as they an important indicator of illness severity and therapeutic response.8 Not only was there a significant increase in the rate of lactate measurement in the Sepsis Pathway Group compared to the Control Group (92.3% vs 64%, OR 6.74, 95% CI 2.30–19.80, p=0.0005), but the time to lactate measurement was also shorter; the median time to lactate measurement was 54.5 minutes in the Sepsis Pathway Group compared to 64 minutes in the control group. Also, the proportion of patients who had their lactate measured within the target of 60 minutes after triage almost doubled from 27.3% prior to the pathway to 53.8% in the Sepsis Pathway Group (OR 2.86, 95% CI 1.49–5.49, p=0.0016). Blood culture collection rates were also significantly higher in the Sepsis Pathway Group with blood cultures performed on all patients in the group. This indicates that staff may have been prompted to perform lactate levels and blood cultures by the complementary Sepsis Pack, which included equipment for intravenous cannulation, lactate measurement and blood cultures.

The initial investigation and management with antibiotics of septic patients improved when the Sepsis Pathway was used. However, this did not have a significant effect on outcomes such as duration of ICU admission and length of hospital stay. There was also an increase in mortality and ICU admission rates in septic patients where the Sepsis Pathway was used; however, this was not statistically significant.

The predominant presenting problems both pre- and post-protocol were non-specific, including fever/pyrexia of unknown origin, shortness of breath and generally unwell. More timely recognition of potential sepsis in these patients may lead to further improvements in time to antibiotic and investigation, with subsequent improvements in ICU rates and mortality.1,2

The moment a patient presents to the emergency department, they are classified into a Triage Category, which affects how quickly they are seen by a clinician in the department. A greater index of suspicion that patients are potentially septic, especially in those with non-specific presenting problems, may lead to expedition of their investigation and management, including allocation to more urgent triage categories. This has a flow-on effect as these patients are likely to be seen by a clinician earlier, have investigations performed more promptly and receive empirical antibiotics earlier. This effect should be further evaluated to see whether the introduction of the Sepsis Pathway and its effect on the Triage Category has a causational effect on antibiotic administration times and time to investigations. Further work is required to examine the confounding effect of a generally higher triage category on time to antibiotics and investigations.

Additionally, the Sepsis Pathway, as aforementioned should risk stratify patients. This will ensure that cases that are more severe are prioritised. Although patients that were septic were identified, further investigations should be explored in future studies to assess the degree of organ dysfunction that has occurred as a result of sepsis. Markers of organ and tissue dysfunction such as those included in the SOFA score (eg, serum creatinine, bilirubin and platelet count) may be useful in determining the risk of adverse outcomes. This could be included in further studies9  (Table 5).

Table 5: Summary.

Limitations

This study was conducted at a single health service across three sites and is subsequently limited by a small study size. As with other quality improvement programmes and especially in the emergency department where staff turnover is high, the improved outcomes may also be related to other factors. Staff experience, knowledge of sepsis and the recent sepsis recognition awareness training within the hospital are potential confounders. Moreover, this study was conducted after the Monash Health Sepsis Pathway Project was established. Naturally as a result of this, there was some delay in publishing the results obtained.

Our data collection involved the time antibiotics were given but did not include the time antibiotics were prescribed. Without knowing the time a decision was made to give antibiotics, it is difficult to identify the cause of the delay in antibiotic administration. This could be due to the antibiotics not being prescribed early enough or due to a delay in administration. Additionally, data collection did not include time from onset of symptoms to presentation to the emergency department as this was not always documented. Ideally, this should be considered as this will impact on results. Similarly, the origin of sepsis was also not often known and therefore could not be analysed as a variable that may affect outcomes.

Septic patients were also not separated in terms of antibiotic protocol used, however this can be considered in further study.

As the selection of patients in the control group is retrospective in nature, identification of patients is subject to selection bias. This is demonstrated by a slight difference in age between the pre-intervention group and Sepsis Pathway and Missed Cases groups. We recognise that age could be a confounder as a result. We attempted to reduce this bias, however by ensuring that all cases that were identified through blood cultures were not false positives.

Due to the importance of quick biomarker results in this critically unwell septic cohort, venous blood gas lactate was used in this study. The accuracy of lactate measurement might vary based on the sample site, however strong correlation between arterial, central vein and peripheral vein lactate as well as other parameter with laboratory blood tests was demonstrated in previous studies.10,11

Conclusions

Implementation of the Sepsis Pathway led to earlier recognition, the lactate being measured more often and earlier administration of antibiotics in patients presenting to the emergency department with suspected sepsis. Nonetheless, this did not influence frequency of ICU admission or hospital length of stay.

There are still delays in the recognition of sepsis and initiation of investigation and management. Further evaluation of the Sepsis Pathway in a larger multi-centre study, also evaluating duration from the time a patient is first seen by a clinician rather than from triage, is warranted.

Summary

Abstract

Aim

Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. We aimed to study the effect of the Sepsis Pathway Programme, a set of guidelines for sepsis, on the recognition, early investigation and management of septic patients in the emergency department.

Method

We conducted a comparative prospective cohort study of patients who presented with suspected sepsis pre- and post-implementation of the Sepsis Pathway. Patients where the Sepsis Pathway was used were identified and followed prospectively to analyse outcomes. This group was compared to a pre-intervention control group who were identified retrospectively before the Sepsis Pathway was implemented to determine if there was any difference in outcomes.

Results

A total of 109 patients were identified to be septic in the emergency department following the implementation of the Sepsis Pathway. Of these, 52 cases involved the initiation and completion of the Sepsis Pathway. One hundred and fifty-seven cases were identified in the pre-intervention group of which 18 cases were excluded. The time to antibiotic administration decreased from 182 to 75 minutes (p<0.00001). The proportion of cases where antibiotics were given within the hour was higher in the pathway group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69–13.81, p<0.0001). Similarly, the time to lactate measurement decreased from 64 minutes to 54.5 minutes (p=0.0117) and the proportion of cases where lactate was measured improved from 64% to 92.3% (p=0.0005). Blood culture rates improved from 79.1% to 100%.

Conclusion

The implementation of the Sepsis Pathway improved time taken to perform investigations and manage patients with sepsis. Although it had improved, there was still a delay in recognition of sepsis and initiation of investigations and management, demonstrating that further strategies need to be employed to reduce poor outcomes associated with sepsis. However, it did not affect ICU admissions, length of stay or mortality.

Author Information

Pourya Pouryahya, Casey Hospital, Emergency Department, Programme of Emergency Medicine, Monash Health, Victoria; Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria; Natalie Guiney, Bendigo Health, Victoria; Alastair Meyer, Casey Hospital, Emergency Department, Programme of Emergency Medicine, Monash Health, Victoria; Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria; Neil Goldie, Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria.

Acknowledgements

Special thanks to all Casey Hospital emergency department team and Monash Health sepsis group for their support during this study.

Correspondence

Dr Pourya Pouryahya, Casey Hospital, 62 Kangan Drive, Berwick, Victoria 3806.

Correspondence Email

pourya.pouryahya@monashhealth.org

Competing Interests

Nil.

1. Damiani E, Donati A, Serafini G, Rinaldi L, Adrario E, Pelaia P, et al. Effect of Performance Improvement Programs on Compliance with Sepsis Bundles and Mortality: A Systematic Review and Meta-Analysis of Observational Studies. PLOS ONE. 2015; 10(5):e0125827.

2. Levy M, Dellinger R, Townsend S, Linde-Zwirble W, Marshall J, Bion J, et al. The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Critical Care Medicine. 2010; 38(2):367–374.

3. Rhodes A, Evans L, Alhazzani W, Levy M, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Critical Care Medicine. 2017; 45(3):486–552.

4. Observation and Response Charts | Safety and Quality [Internet]. Safetyandquality.gov.au. 2017 [cited 9 March 2017]. Available from: http://www.safetyandquality.gov.au/our-work/recognising-and-responding-to-clinical-deterioration/observation-and-response-charts/

5. Guidelines on the implementation of the Australasian Triage Scale in Emergency Departments [Internet]. Acem.org.au. 2016 [cited 9 March 2017]. Available from: http://acem.org.au/getattachment/4320524e-ad60-4e7c-a96d-bdf90cd7966c/G24-Implementation-of-the-Australasian-Triage-Scal.aspx

6. Burrell A, McLaws M, Fullick M, Sullivan R, Sindhusake D. SEPSIS KILLS: early intervention saves lives. The Medical Journal of Australia. 2016; 204(2):73.

7. Ferrer R, Martin-Loeches I, Phillips G, Osborn T, Townsend S, Dellinger R et al. Empiric Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock From the First Hour. Critical Care Medicine. 2014; 42(8):1749–1755.

8. Singer M. Deutschmann C, Seymour C, Shankar-Hari M, Annane D, Bauer M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8):801

9. Shetty A, Macdonald S, Keijzers G, Williams J, Tang B, Bas de Grout, et al. Sepsis in the emergency department- Part 2: Investigations and monitoring. Emergency Medicine Australasia. 2018; 30(1):4–12.

10. Velissaris D, Karamouzos V, Pantzaris ND, Kyriakopoulou O, Gogos C, Karanikolas M. Relation Between Central Venous, Peripheral Venous and Arterial Lactate Levels in Patients with Sepsis in the Emergency Department: J Clin Med Res. 2019 Sep; 11(9):629–634.

11. Pouryahya P, Tan Lynn, Lin Caleb, Meyer A. Reliability of venous blood gas Sodium, Potassium and Creatinine. NZMJ 14 December 2018; 131(1487):38–43.

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Although sepsis is well recognised as a medical emergency, it can be difficult to identify given its various clinical presentations. Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. These are also key components in international guidelines for managing sepsis.1–3

A set of guidelines for sepsis known as the Sepsis Pathway (Figure 1) was included in a pre-formed pack of equipment and introduced in three emergency departments—Monash Medical Centre (tertiary hospital), Dandenong Hospital and Casey Hospital (district hospitals) in June 2015. This aimed to promote early recognition and response to patients with potential sepsis. It details steps to assist clinicians to: i) recognise, ii) respond and escalate, iii) resuscitate and reassess, and iv) refer septic patients. After ethics approval the first Victorian sepsis pathway was developed by the Monash health multidisciplinary sepsis group. Monash Health is the largest health network in the state of Victoria, Australia, with an annual emergency department network census of about 200,000 presentations. It comprises of three hospitals: Monash Medical Centre (tertiary referral), Dandenong and Casey hospitals (district hospitals).

Figure 1: Sepsis flowchart checklist.

To assist with the recognition of sepsis, the guideline includes a checklist of vital sign parameters, which vary slightly from the well-known Systemic Inflammatory Response Criteria, but are aligned with Australian Observation and Response Charts.4 The Guideline suggests responding to patients with two or more observations that fall within the set criteria with a review by a senior clinician within 30 minutes.

The pathway advises collection of blood for multiple tests including two sets of blood cultures, a venous blood gas and a lactate level. However, it also emphasises that administration of empirical antibiotics for sepsis should not be delayed by investigations or results (Figure 2).

Figure 2: Sepsis management plan.

The Sepsis Pathway was introduced as part of a Sepsis Pack, designed to support clinicians in performing the steps outlined in the guideline. The Sepsis Pack includes equipment for intravenous cannulation and intravenous fluids, as well as for collection of blood for culture and lactate measurement.

This article evaluates the impact of the implementation of the Sepsis Pathway Programme on the recognition, early investigation and management of septic patients in the emergency department.

Methods

The aim of this pathway was to improve recognition of patients with sepsis (RECOGNISE) and to initiate early management with intravenous fluid and antimicrobial therapy (REACT). The Sepsis Pathway was designed with broad inclusion criteria to identify sepsis as well as risk stratify potential septic patients. There are a set of risk factors based on history and physical examination to identify high-risk patients:

• Immunocompromised/chronic illness/chemotherapy/radiotherapy

• Abdominal pain/distension/peritonism

• Indwelling medical device

• Cough/sputum/breathlessness

• Recent surgery/invasive procedure

• New onset of confusion/altered LOC/neck stiffness/headache

• History of fever or rigors

• Re-presentation within 48 hours

• Wound infection/cellulitis

• Fall not related to mechanism of injury

• Dysuria/frequency/odour

• Age >65yo

This, in conjunction with the analysis of the patients’ vital signs can be used to risk stratify patients. Vital signs triggering the initiation of Sepsis Pathway are as follows:

• Respirations ≤10 or ≥25 per minute

• SpO2 ≤95%

• Systolic blood pressure ≤100mmHg

• Heart rate ≤50 or ≥120 per minute

• Altered LOC or new onset of confusion

• Temp <35.5 °C or >38.5 °C

High-risk patients are identified if:

• Lactate ≥4mmol/L

• Immunocompromised

• SBP ≤90mmHg

• Base excess <-5.0

After identification of a septic or potentially septic patient, the pathway is strictly followed.

An explicit Sepsis Data Collection Form to assess the effect of the Sepsis Pathway was added to Sepsis Packs at Casey Hospital, a district hospital with mixed emergency department (adults and paediatrics) with about 60,000 presentations annually. A comparative prospective cohort study of patients presenting with suspected sepsis pre- and post-implementation of the Sepsis Pathway was then conducted. This was in conjunction with multidisciplinary Monash Health sepsis pathway development programme, which was approved by the ethics committee. From June to December 2015, data was collected prospectively for patients who were identified in the emergency department to have potential sepsis. The outcomes were measured for groups where the Sepsis Pathway was used and not used. Cases where a diagnosis of sepsis was missed in the emergency department were identified through a search of electronic medical records (EMR) looking for all patients subsequently diagnosed with sepsis as well as those that had documented positive blood cultures during admission. Those with growth on blood culture of a gram-positive cocci were excluded from this group as they were considered false positives due to likely contamination.

These groups were compared to a control group which included patients with suspected sepsis who presented to the same emergency department from June to December 2014, a year prior to the implementation of the Sepsis Pathway. These patients were identified through a search of EMR looking for patients who were diagnosed with sepsis in the emergency department. Those cases that were missed in the emergency department were also included. They were identified through a search of the EMR looking for patients diagnosed with sepsis throughout their admission or those had positive blood cultures during admission. Similar to above, false positives were duly accounted for and excluded as any growth of gram-positive cocci were considered most likely contaminated samples. We compared the control group (2014) to the group of patients specifically placed on the Sepsis Pathway (2015), as well as those that were missed and later identified through EMR during the intervention period. Patients <18 years old, those who were already taking a course of antibiotics as an outpatient prior to their presentation and those that were transferred to other hospitals during admission were excluded from the study.

The following data was collected:

• Date of birth

• Triage time and date

• Triage category

• Presenting problem at triage

• Time to antibiotic from time of triage

• Time to lactate measurement from time of triage

• Number of cases where blood cultures were taken

• Number of intensive care admissions

• Length of intensive care admission

• Length of hospital admission

• In-hospital mortality

Analysis included the calculation of odds ratios with 95% confidence intervals according to Altman and p-values using Fisher’s exact and t test. Statistical significance was defined as p<0.05.

Results

Following the introduction of the Sepsis Pathway, a total of 109 patients were identified to be septic, either at presentation in the emergency department or throughout admission during the study period of 15 June to 31 December 2015. Of these, 52 cases were identified prospectively to be septic through the initiation and completion of the Sepsis Pathway Collection Form. This group will be referred to as the ‘Sepsis Pathway’ Group. It also includes patients who were identified and treated as septic, and subsequently transferred to intensive care unit from the emergency department. The remaining cases were either those identified with sepsis in the emergency department but were not treated with the Sepsis Pathway or those that were missed and identified to be septic throughout their admission. These groups were identified to have sepsis through a retrospective search of the EMR using positive blood cultures collected on presentation or during their admission. The missed cases that had gram-positive cocci grown on blood culture were excluded as they were presumed to be contaminated samples and could bias the data. This group will be referred to as the ‘Missed Cases Group’. The pre-intervention control group included 139 patients who presented from 15 June to 31 December 2014. They were either identified in the emergency department to be septic, were documented as septic during their admission or had a true positive blood culture, again excluding any cases that could be contaminated (gram positive cocci growth on blood culture).

Figure 3: Breakdown of the septic patients for both the control and intervention group.

The Pre-intervention Control Group (2014) had a median age of 78 (IQR 56–91). Patients in the ‘Sepsis Pathway Group (2015)’ and the ‘Missed Cases Group (2015)’ had a median age of 67 (IQR 53.75–81) and 69 (IQR 50–84), respectively.

In the study period prior to the implementation of the Sepsis Pathway, there was a significantly lower proportion of septic patients who were triaged as Category 1 according to the Australasian Triage Scale (ATS) from no cases in the pre-intervention period to three cases in the Sepsis Pathway Group (0% vs 5.8%, p=0.0193).5

Figure 4: Comparison of the triage categories.

The three most common presenting problems in all groups were ‘febrile/PUO’ (17.8% of all cases), ‘shortness of breath’ (13.9% of all cases) and ‘generally unwell’ (15.4% of all cases).

Table 1: The three most common presenting problems.

The median time to antibiotic administration in the Sepsis Pathway Group improved significantly compared to the Control Group (75 minutes vs 182 minutes, p<0.00001). The proportion of patients who received antibiotics within 60 minutes of triage was greater in the Sepsis Pathway Group than in the pre-intervention group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69–13.81, p<0.0001).

Figure 5: Antibiotics administered within the hour.

Similarly, the median time to lactate measurement was significantly shorter in the Sepsis Pathway Group compared to the pre-intervention group (54.5 minutes vs. 64 minutes, p=0.0117). A greater proportion of patients had their lactate measured within 60 minutes of triage in the Sepsis Pathway Group than in the pre-intervention group and this was statistically significant (53.8% vs 27.3%, OR 2.86, 95% CI 1.49–5.49, p=0.0016).

Figure 6: Lactate measured within the hour.

Table 2: Median time to antibiotics administration and lactate measurement.

Serum lactate levels were tested more often in the Sepsis Pathway Group than in the Control Group (92.3% vs 64.0%, OR 6.74, 95% CI 2.30–19.80, p=0.0005). Blood cultures were sent in all of the cases that utilised the Sepsis Pathway; 20.9% of the cases in the pre-implementation group did not have blood cultures taken during their admission.

Table 3: Number of blood culture and lactate done in each group.

There was an increase in the rate of ICU admission in the Sepsis Pathway group when compared to the pre-intervention group; however, this was not statistically significant (28.8% vs 16.5%, OR 1.94, 95% CI 0.92–4.09, p=0.0823).

No significant differences were seen between the groups when looking at the median length of stay in ICU, length of hospital admission or mortality.

Table 4: ICU admission rates and length of stay, hospital length of stay and mortality comparison.

Discussion

Recognition of sepsis and the importance of prompt management appear to have improved following the introduction of the Sepsis Pathway Flowchart. This is demonstrated by the reduction of missed cases in the emergency department following the implementation of the Sepsis Pathway when compared to the pre-implementation phase (69.1% vs 20.5%). This decrease could be due to the guideline being presented as a checklist to medical staff, allowing doctors to follow it easily even when they are unsure. Though there is a decrease in the number of missed cases after the implementation of the Sepsis Pathway, there is still room for improvement. False negatives remain with non-specific presentations or early presenting features not covered by the checklist. Additionally, in 2015, more patients were triaged as Category 1 and 2 compared to prior to the implementation of the Sepsis Pathway (38.5% vs 22.3%). Being classified in a more urgent Triage Category, these patients are more likely to be seen by a clinician earlier and subsequently, investigation and management may be initiated earlier. Previous sepsis quality improvement programmes have also resulted in increases in the number of patients in higher urgency triage categories, such as ATS 1 or 2, and there were also reciprocal reductions in less urgent triage categories.5

In sepsis, delay in administration of appropriate antibiotics is associated with increased mortality. Commencing appropriate antibiotic therapy as soon as possible in septic patients is ideal, with international guidelines recommending one hour as a reasonable minimal target.3,7 The median time to antibiotic administration was shorter in the Sepsis Pathway Group with significantly more patients receiving antibiotics within 60 minutes of being triaged. However, the median time remained suboptimal even after the introduction of the Sepsis Pathway with 64.5% of antibiotic administration times exceeding the target of 60 minutes.

There has been a recent change in the classification of sepsis, with the introduction of the sepsis 3 criteria. Lactate levels are included in the clinical criteria for septic shock as they an important indicator of illness severity and therapeutic response.8 Not only was there a significant increase in the rate of lactate measurement in the Sepsis Pathway Group compared to the Control Group (92.3% vs 64%, OR 6.74, 95% CI 2.30–19.80, p=0.0005), but the time to lactate measurement was also shorter; the median time to lactate measurement was 54.5 minutes in the Sepsis Pathway Group compared to 64 minutes in the control group. Also, the proportion of patients who had their lactate measured within the target of 60 minutes after triage almost doubled from 27.3% prior to the pathway to 53.8% in the Sepsis Pathway Group (OR 2.86, 95% CI 1.49–5.49, p=0.0016). Blood culture collection rates were also significantly higher in the Sepsis Pathway Group with blood cultures performed on all patients in the group. This indicates that staff may have been prompted to perform lactate levels and blood cultures by the complementary Sepsis Pack, which included equipment for intravenous cannulation, lactate measurement and blood cultures.

The initial investigation and management with antibiotics of septic patients improved when the Sepsis Pathway was used. However, this did not have a significant effect on outcomes such as duration of ICU admission and length of hospital stay. There was also an increase in mortality and ICU admission rates in septic patients where the Sepsis Pathway was used; however, this was not statistically significant.

The predominant presenting problems both pre- and post-protocol were non-specific, including fever/pyrexia of unknown origin, shortness of breath and generally unwell. More timely recognition of potential sepsis in these patients may lead to further improvements in time to antibiotic and investigation, with subsequent improvements in ICU rates and mortality.1,2

The moment a patient presents to the emergency department, they are classified into a Triage Category, which affects how quickly they are seen by a clinician in the department. A greater index of suspicion that patients are potentially septic, especially in those with non-specific presenting problems, may lead to expedition of their investigation and management, including allocation to more urgent triage categories. This has a flow-on effect as these patients are likely to be seen by a clinician earlier, have investigations performed more promptly and receive empirical antibiotics earlier. This effect should be further evaluated to see whether the introduction of the Sepsis Pathway and its effect on the Triage Category has a causational effect on antibiotic administration times and time to investigations. Further work is required to examine the confounding effect of a generally higher triage category on time to antibiotics and investigations.

Additionally, the Sepsis Pathway, as aforementioned should risk stratify patients. This will ensure that cases that are more severe are prioritised. Although patients that were septic were identified, further investigations should be explored in future studies to assess the degree of organ dysfunction that has occurred as a result of sepsis. Markers of organ and tissue dysfunction such as those included in the SOFA score (eg, serum creatinine, bilirubin and platelet count) may be useful in determining the risk of adverse outcomes. This could be included in further studies9  (Table 5).

Table 5: Summary.

Limitations

This study was conducted at a single health service across three sites and is subsequently limited by a small study size. As with other quality improvement programmes and especially in the emergency department where staff turnover is high, the improved outcomes may also be related to other factors. Staff experience, knowledge of sepsis and the recent sepsis recognition awareness training within the hospital are potential confounders. Moreover, this study was conducted after the Monash Health Sepsis Pathway Project was established. Naturally as a result of this, there was some delay in publishing the results obtained.

Our data collection involved the time antibiotics were given but did not include the time antibiotics were prescribed. Without knowing the time a decision was made to give antibiotics, it is difficult to identify the cause of the delay in antibiotic administration. This could be due to the antibiotics not being prescribed early enough or due to a delay in administration. Additionally, data collection did not include time from onset of symptoms to presentation to the emergency department as this was not always documented. Ideally, this should be considered as this will impact on results. Similarly, the origin of sepsis was also not often known and therefore could not be analysed as a variable that may affect outcomes.

Septic patients were also not separated in terms of antibiotic protocol used, however this can be considered in further study.

As the selection of patients in the control group is retrospective in nature, identification of patients is subject to selection bias. This is demonstrated by a slight difference in age between the pre-intervention group and Sepsis Pathway and Missed Cases groups. We recognise that age could be a confounder as a result. We attempted to reduce this bias, however by ensuring that all cases that were identified through blood cultures were not false positives.

Due to the importance of quick biomarker results in this critically unwell septic cohort, venous blood gas lactate was used in this study. The accuracy of lactate measurement might vary based on the sample site, however strong correlation between arterial, central vein and peripheral vein lactate as well as other parameter with laboratory blood tests was demonstrated in previous studies.10,11

Conclusions

Implementation of the Sepsis Pathway led to earlier recognition, the lactate being measured more often and earlier administration of antibiotics in patients presenting to the emergency department with suspected sepsis. Nonetheless, this did not influence frequency of ICU admission or hospital length of stay.

There are still delays in the recognition of sepsis and initiation of investigation and management. Further evaluation of the Sepsis Pathway in a larger multi-centre study, also evaluating duration from the time a patient is first seen by a clinician rather than from triage, is warranted.

Summary

Abstract

Aim

Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. We aimed to study the effect of the Sepsis Pathway Programme, a set of guidelines for sepsis, on the recognition, early investigation and management of septic patients in the emergency department.

Method

We conducted a comparative prospective cohort study of patients who presented with suspected sepsis pre- and post-implementation of the Sepsis Pathway. Patients where the Sepsis Pathway was used were identified and followed prospectively to analyse outcomes. This group was compared to a pre-intervention control group who were identified retrospectively before the Sepsis Pathway was implemented to determine if there was any difference in outcomes.

Results

A total of 109 patients were identified to be septic in the emergency department following the implementation of the Sepsis Pathway. Of these, 52 cases involved the initiation and completion of the Sepsis Pathway. One hundred and fifty-seven cases were identified in the pre-intervention group of which 18 cases were excluded. The time to antibiotic administration decreased from 182 to 75 minutes (p<0.00001). The proportion of cases where antibiotics were given within the hour was higher in the pathway group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69–13.81, p<0.0001). Similarly, the time to lactate measurement decreased from 64 minutes to 54.5 minutes (p=0.0117) and the proportion of cases where lactate was measured improved from 64% to 92.3% (p=0.0005). Blood culture rates improved from 79.1% to 100%.

Conclusion

The implementation of the Sepsis Pathway improved time taken to perform investigations and manage patients with sepsis. Although it had improved, there was still a delay in recognition of sepsis and initiation of investigations and management, demonstrating that further strategies need to be employed to reduce poor outcomes associated with sepsis. However, it did not affect ICU admissions, length of stay or mortality.

Author Information

Pourya Pouryahya, Casey Hospital, Emergency Department, Programme of Emergency Medicine, Monash Health, Victoria; Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria; Natalie Guiney, Bendigo Health, Victoria; Alastair Meyer, Casey Hospital, Emergency Department, Programme of Emergency Medicine, Monash Health, Victoria; Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria; Neil Goldie, Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria.

Acknowledgements

Special thanks to all Casey Hospital emergency department team and Monash Health sepsis group for their support during this study.

Correspondence

Dr Pourya Pouryahya, Casey Hospital, 62 Kangan Drive, Berwick, Victoria 3806.

Correspondence Email

pourya.pouryahya@monashhealth.org

Competing Interests

Nil.

1. Damiani E, Donati A, Serafini G, Rinaldi L, Adrario E, Pelaia P, et al. Effect of Performance Improvement Programs on Compliance with Sepsis Bundles and Mortality: A Systematic Review and Meta-Analysis of Observational Studies. PLOS ONE. 2015; 10(5):e0125827.

2. Levy M, Dellinger R, Townsend S, Linde-Zwirble W, Marshall J, Bion J, et al. The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Critical Care Medicine. 2010; 38(2):367–374.

3. Rhodes A, Evans L, Alhazzani W, Levy M, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Critical Care Medicine. 2017; 45(3):486–552.

4. Observation and Response Charts | Safety and Quality [Internet]. Safetyandquality.gov.au. 2017 [cited 9 March 2017]. Available from: http://www.safetyandquality.gov.au/our-work/recognising-and-responding-to-clinical-deterioration/observation-and-response-charts/

5. Guidelines on the implementation of the Australasian Triage Scale in Emergency Departments [Internet]. Acem.org.au. 2016 [cited 9 March 2017]. Available from: http://acem.org.au/getattachment/4320524e-ad60-4e7c-a96d-bdf90cd7966c/G24-Implementation-of-the-Australasian-Triage-Scal.aspx

6. Burrell A, McLaws M, Fullick M, Sullivan R, Sindhusake D. SEPSIS KILLS: early intervention saves lives. The Medical Journal of Australia. 2016; 204(2):73.

7. Ferrer R, Martin-Loeches I, Phillips G, Osborn T, Townsend S, Dellinger R et al. Empiric Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock From the First Hour. Critical Care Medicine. 2014; 42(8):1749–1755.

8. Singer M. Deutschmann C, Seymour C, Shankar-Hari M, Annane D, Bauer M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8):801

9. Shetty A, Macdonald S, Keijzers G, Williams J, Tang B, Bas de Grout, et al. Sepsis in the emergency department- Part 2: Investigations and monitoring. Emergency Medicine Australasia. 2018; 30(1):4–12.

10. Velissaris D, Karamouzos V, Pantzaris ND, Kyriakopoulou O, Gogos C, Karanikolas M. Relation Between Central Venous, Peripheral Venous and Arterial Lactate Levels in Patients with Sepsis in the Emergency Department: J Clin Med Res. 2019 Sep; 11(9):629–634.

11. Pouryahya P, Tan Lynn, Lin Caleb, Meyer A. Reliability of venous blood gas Sodium, Potassium and Creatinine. NZMJ 14 December 2018; 131(1487):38–43.

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Although sepsis is well recognised as a medical emergency, it can be difficult to identify given its various clinical presentations. Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. These are also key components in international guidelines for managing sepsis.1–3

A set of guidelines for sepsis known as the Sepsis Pathway (Figure 1) was included in a pre-formed pack of equipment and introduced in three emergency departments—Monash Medical Centre (tertiary hospital), Dandenong Hospital and Casey Hospital (district hospitals) in June 2015. This aimed to promote early recognition and response to patients with potential sepsis. It details steps to assist clinicians to: i) recognise, ii) respond and escalate, iii) resuscitate and reassess, and iv) refer septic patients. After ethics approval the first Victorian sepsis pathway was developed by the Monash health multidisciplinary sepsis group. Monash Health is the largest health network in the state of Victoria, Australia, with an annual emergency department network census of about 200,000 presentations. It comprises of three hospitals: Monash Medical Centre (tertiary referral), Dandenong and Casey hospitals (district hospitals).

Figure 1: Sepsis flowchart checklist.

To assist with the recognition of sepsis, the guideline includes a checklist of vital sign parameters, which vary slightly from the well-known Systemic Inflammatory Response Criteria, but are aligned with Australian Observation and Response Charts.4 The Guideline suggests responding to patients with two or more observations that fall within the set criteria with a review by a senior clinician within 30 minutes.

The pathway advises collection of blood for multiple tests including two sets of blood cultures, a venous blood gas and a lactate level. However, it also emphasises that administration of empirical antibiotics for sepsis should not be delayed by investigations or results (Figure 2).

Figure 2: Sepsis management plan.

The Sepsis Pathway was introduced as part of a Sepsis Pack, designed to support clinicians in performing the steps outlined in the guideline. The Sepsis Pack includes equipment for intravenous cannulation and intravenous fluids, as well as for collection of blood for culture and lactate measurement.

This article evaluates the impact of the implementation of the Sepsis Pathway Programme on the recognition, early investigation and management of septic patients in the emergency department.

Methods

The aim of this pathway was to improve recognition of patients with sepsis (RECOGNISE) and to initiate early management with intravenous fluid and antimicrobial therapy (REACT). The Sepsis Pathway was designed with broad inclusion criteria to identify sepsis as well as risk stratify potential septic patients. There are a set of risk factors based on history and physical examination to identify high-risk patients:

• Immunocompromised/chronic illness/chemotherapy/radiotherapy

• Abdominal pain/distension/peritonism

• Indwelling medical device

• Cough/sputum/breathlessness

• Recent surgery/invasive procedure

• New onset of confusion/altered LOC/neck stiffness/headache

• History of fever or rigors

• Re-presentation within 48 hours

• Wound infection/cellulitis

• Fall not related to mechanism of injury

• Dysuria/frequency/odour

• Age >65yo

This, in conjunction with the analysis of the patients’ vital signs can be used to risk stratify patients. Vital signs triggering the initiation of Sepsis Pathway are as follows:

• Respirations ≤10 or ≥25 per minute

• SpO2 ≤95%

• Systolic blood pressure ≤100mmHg

• Heart rate ≤50 or ≥120 per minute

• Altered LOC or new onset of confusion

• Temp <35.5 °C or >38.5 °C

High-risk patients are identified if:

• Lactate ≥4mmol/L

• Immunocompromised

• SBP ≤90mmHg

• Base excess <-5.0

After identification of a septic or potentially septic patient, the pathway is strictly followed.

An explicit Sepsis Data Collection Form to assess the effect of the Sepsis Pathway was added to Sepsis Packs at Casey Hospital, a district hospital with mixed emergency department (adults and paediatrics) with about 60,000 presentations annually. A comparative prospective cohort study of patients presenting with suspected sepsis pre- and post-implementation of the Sepsis Pathway was then conducted. This was in conjunction with multidisciplinary Monash Health sepsis pathway development programme, which was approved by the ethics committee. From June to December 2015, data was collected prospectively for patients who were identified in the emergency department to have potential sepsis. The outcomes were measured for groups where the Sepsis Pathway was used and not used. Cases where a diagnosis of sepsis was missed in the emergency department were identified through a search of electronic medical records (EMR) looking for all patients subsequently diagnosed with sepsis as well as those that had documented positive blood cultures during admission. Those with growth on blood culture of a gram-positive cocci were excluded from this group as they were considered false positives due to likely contamination.

These groups were compared to a control group which included patients with suspected sepsis who presented to the same emergency department from June to December 2014, a year prior to the implementation of the Sepsis Pathway. These patients were identified through a search of EMR looking for patients who were diagnosed with sepsis in the emergency department. Those cases that were missed in the emergency department were also included. They were identified through a search of the EMR looking for patients diagnosed with sepsis throughout their admission or those had positive blood cultures during admission. Similar to above, false positives were duly accounted for and excluded as any growth of gram-positive cocci were considered most likely contaminated samples. We compared the control group (2014) to the group of patients specifically placed on the Sepsis Pathway (2015), as well as those that were missed and later identified through EMR during the intervention period. Patients <18 years old, those who were already taking a course of antibiotics as an outpatient prior to their presentation and those that were transferred to other hospitals during admission were excluded from the study.

The following data was collected:

• Date of birth

• Triage time and date

• Triage category

• Presenting problem at triage

• Time to antibiotic from time of triage

• Time to lactate measurement from time of triage

• Number of cases where blood cultures were taken

• Number of intensive care admissions

• Length of intensive care admission

• Length of hospital admission

• In-hospital mortality

Analysis included the calculation of odds ratios with 95% confidence intervals according to Altman and p-values using Fisher’s exact and t test. Statistical significance was defined as p<0.05.

Results

Following the introduction of the Sepsis Pathway, a total of 109 patients were identified to be septic, either at presentation in the emergency department or throughout admission during the study period of 15 June to 31 December 2015. Of these, 52 cases were identified prospectively to be septic through the initiation and completion of the Sepsis Pathway Collection Form. This group will be referred to as the ‘Sepsis Pathway’ Group. It also includes patients who were identified and treated as septic, and subsequently transferred to intensive care unit from the emergency department. The remaining cases were either those identified with sepsis in the emergency department but were not treated with the Sepsis Pathway or those that were missed and identified to be septic throughout their admission. These groups were identified to have sepsis through a retrospective search of the EMR using positive blood cultures collected on presentation or during their admission. The missed cases that had gram-positive cocci grown on blood culture were excluded as they were presumed to be contaminated samples and could bias the data. This group will be referred to as the ‘Missed Cases Group’. The pre-intervention control group included 139 patients who presented from 15 June to 31 December 2014. They were either identified in the emergency department to be septic, were documented as septic during their admission or had a true positive blood culture, again excluding any cases that could be contaminated (gram positive cocci growth on blood culture).

Figure 3: Breakdown of the septic patients for both the control and intervention group.

The Pre-intervention Control Group (2014) had a median age of 78 (IQR 56–91). Patients in the ‘Sepsis Pathway Group (2015)’ and the ‘Missed Cases Group (2015)’ had a median age of 67 (IQR 53.75–81) and 69 (IQR 50–84), respectively.

In the study period prior to the implementation of the Sepsis Pathway, there was a significantly lower proportion of septic patients who were triaged as Category 1 according to the Australasian Triage Scale (ATS) from no cases in the pre-intervention period to three cases in the Sepsis Pathway Group (0% vs 5.8%, p=0.0193).5

Figure 4: Comparison of the triage categories.

The three most common presenting problems in all groups were ‘febrile/PUO’ (17.8% of all cases), ‘shortness of breath’ (13.9% of all cases) and ‘generally unwell’ (15.4% of all cases).

Table 1: The three most common presenting problems.

The median time to antibiotic administration in the Sepsis Pathway Group improved significantly compared to the Control Group (75 minutes vs 182 minutes, p<0.00001). The proportion of patients who received antibiotics within 60 minutes of triage was greater in the Sepsis Pathway Group than in the pre-intervention group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69–13.81, p<0.0001).

Figure 5: Antibiotics administered within the hour.

Similarly, the median time to lactate measurement was significantly shorter in the Sepsis Pathway Group compared to the pre-intervention group (54.5 minutes vs. 64 minutes, p=0.0117). A greater proportion of patients had their lactate measured within 60 minutes of triage in the Sepsis Pathway Group than in the pre-intervention group and this was statistically significant (53.8% vs 27.3%, OR 2.86, 95% CI 1.49–5.49, p=0.0016).

Figure 6: Lactate measured within the hour.

Table 2: Median time to antibiotics administration and lactate measurement.

Serum lactate levels were tested more often in the Sepsis Pathway Group than in the Control Group (92.3% vs 64.0%, OR 6.74, 95% CI 2.30–19.80, p=0.0005). Blood cultures were sent in all of the cases that utilised the Sepsis Pathway; 20.9% of the cases in the pre-implementation group did not have blood cultures taken during their admission.

Table 3: Number of blood culture and lactate done in each group.

There was an increase in the rate of ICU admission in the Sepsis Pathway group when compared to the pre-intervention group; however, this was not statistically significant (28.8% vs 16.5%, OR 1.94, 95% CI 0.92–4.09, p=0.0823).

No significant differences were seen between the groups when looking at the median length of stay in ICU, length of hospital admission or mortality.

Table 4: ICU admission rates and length of stay, hospital length of stay and mortality comparison.

Discussion

Recognition of sepsis and the importance of prompt management appear to have improved following the introduction of the Sepsis Pathway Flowchart. This is demonstrated by the reduction of missed cases in the emergency department following the implementation of the Sepsis Pathway when compared to the pre-implementation phase (69.1% vs 20.5%). This decrease could be due to the guideline being presented as a checklist to medical staff, allowing doctors to follow it easily even when they are unsure. Though there is a decrease in the number of missed cases after the implementation of the Sepsis Pathway, there is still room for improvement. False negatives remain with non-specific presentations or early presenting features not covered by the checklist. Additionally, in 2015, more patients were triaged as Category 1 and 2 compared to prior to the implementation of the Sepsis Pathway (38.5% vs 22.3%). Being classified in a more urgent Triage Category, these patients are more likely to be seen by a clinician earlier and subsequently, investigation and management may be initiated earlier. Previous sepsis quality improvement programmes have also resulted in increases in the number of patients in higher urgency triage categories, such as ATS 1 or 2, and there were also reciprocal reductions in less urgent triage categories.5

In sepsis, delay in administration of appropriate antibiotics is associated with increased mortality. Commencing appropriate antibiotic therapy as soon as possible in septic patients is ideal, with international guidelines recommending one hour as a reasonable minimal target.3,7 The median time to antibiotic administration was shorter in the Sepsis Pathway Group with significantly more patients receiving antibiotics within 60 minutes of being triaged. However, the median time remained suboptimal even after the introduction of the Sepsis Pathway with 64.5% of antibiotic administration times exceeding the target of 60 minutes.

There has been a recent change in the classification of sepsis, with the introduction of the sepsis 3 criteria. Lactate levels are included in the clinical criteria for septic shock as they an important indicator of illness severity and therapeutic response.8 Not only was there a significant increase in the rate of lactate measurement in the Sepsis Pathway Group compared to the Control Group (92.3% vs 64%, OR 6.74, 95% CI 2.30–19.80, p=0.0005), but the time to lactate measurement was also shorter; the median time to lactate measurement was 54.5 minutes in the Sepsis Pathway Group compared to 64 minutes in the control group. Also, the proportion of patients who had their lactate measured within the target of 60 minutes after triage almost doubled from 27.3% prior to the pathway to 53.8% in the Sepsis Pathway Group (OR 2.86, 95% CI 1.49–5.49, p=0.0016). Blood culture collection rates were also significantly higher in the Sepsis Pathway Group with blood cultures performed on all patients in the group. This indicates that staff may have been prompted to perform lactate levels and blood cultures by the complementary Sepsis Pack, which included equipment for intravenous cannulation, lactate measurement and blood cultures.

The initial investigation and management with antibiotics of septic patients improved when the Sepsis Pathway was used. However, this did not have a significant effect on outcomes such as duration of ICU admission and length of hospital stay. There was also an increase in mortality and ICU admission rates in septic patients where the Sepsis Pathway was used; however, this was not statistically significant.

The predominant presenting problems both pre- and post-protocol were non-specific, including fever/pyrexia of unknown origin, shortness of breath and generally unwell. More timely recognition of potential sepsis in these patients may lead to further improvements in time to antibiotic and investigation, with subsequent improvements in ICU rates and mortality.1,2

The moment a patient presents to the emergency department, they are classified into a Triage Category, which affects how quickly they are seen by a clinician in the department. A greater index of suspicion that patients are potentially septic, especially in those with non-specific presenting problems, may lead to expedition of their investigation and management, including allocation to more urgent triage categories. This has a flow-on effect as these patients are likely to be seen by a clinician earlier, have investigations performed more promptly and receive empirical antibiotics earlier. This effect should be further evaluated to see whether the introduction of the Sepsis Pathway and its effect on the Triage Category has a causational effect on antibiotic administration times and time to investigations. Further work is required to examine the confounding effect of a generally higher triage category on time to antibiotics and investigations.

Additionally, the Sepsis Pathway, as aforementioned should risk stratify patients. This will ensure that cases that are more severe are prioritised. Although patients that were septic were identified, further investigations should be explored in future studies to assess the degree of organ dysfunction that has occurred as a result of sepsis. Markers of organ and tissue dysfunction such as those included in the SOFA score (eg, serum creatinine, bilirubin and platelet count) may be useful in determining the risk of adverse outcomes. This could be included in further studies9  (Table 5).

Table 5: Summary.

Limitations

This study was conducted at a single health service across three sites and is subsequently limited by a small study size. As with other quality improvement programmes and especially in the emergency department where staff turnover is high, the improved outcomes may also be related to other factors. Staff experience, knowledge of sepsis and the recent sepsis recognition awareness training within the hospital are potential confounders. Moreover, this study was conducted after the Monash Health Sepsis Pathway Project was established. Naturally as a result of this, there was some delay in publishing the results obtained.

Our data collection involved the time antibiotics were given but did not include the time antibiotics were prescribed. Without knowing the time a decision was made to give antibiotics, it is difficult to identify the cause of the delay in antibiotic administration. This could be due to the antibiotics not being prescribed early enough or due to a delay in administration. Additionally, data collection did not include time from onset of symptoms to presentation to the emergency department as this was not always documented. Ideally, this should be considered as this will impact on results. Similarly, the origin of sepsis was also not often known and therefore could not be analysed as a variable that may affect outcomes.

Septic patients were also not separated in terms of antibiotic protocol used, however this can be considered in further study.

As the selection of patients in the control group is retrospective in nature, identification of patients is subject to selection bias. This is demonstrated by a slight difference in age between the pre-intervention group and Sepsis Pathway and Missed Cases groups. We recognise that age could be a confounder as a result. We attempted to reduce this bias, however by ensuring that all cases that were identified through blood cultures were not false positives.

Due to the importance of quick biomarker results in this critically unwell septic cohort, venous blood gas lactate was used in this study. The accuracy of lactate measurement might vary based on the sample site, however strong correlation between arterial, central vein and peripheral vein lactate as well as other parameter with laboratory blood tests was demonstrated in previous studies.10,11

Conclusions

Implementation of the Sepsis Pathway led to earlier recognition, the lactate being measured more often and earlier administration of antibiotics in patients presenting to the emergency department with suspected sepsis. Nonetheless, this did not influence frequency of ICU admission or hospital length of stay.

There are still delays in the recognition of sepsis and initiation of investigation and management. Further evaluation of the Sepsis Pathway in a larger multi-centre study, also evaluating duration from the time a patient is first seen by a clinician rather than from triage, is warranted.

Summary

Abstract

Aim

Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. We aimed to study the effect of the Sepsis Pathway Programme, a set of guidelines for sepsis, on the recognition, early investigation and management of septic patients in the emergency department.

Method

We conducted a comparative prospective cohort study of patients who presented with suspected sepsis pre- and post-implementation of the Sepsis Pathway. Patients where the Sepsis Pathway was used were identified and followed prospectively to analyse outcomes. This group was compared to a pre-intervention control group who were identified retrospectively before the Sepsis Pathway was implemented to determine if there was any difference in outcomes.

Results

A total of 109 patients were identified to be septic in the emergency department following the implementation of the Sepsis Pathway. Of these, 52 cases involved the initiation and completion of the Sepsis Pathway. One hundred and fifty-seven cases were identified in the pre-intervention group of which 18 cases were excluded. The time to antibiotic administration decreased from 182 to 75 minutes (p<0.00001). The proportion of cases where antibiotics were given within the hour was higher in the pathway group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69–13.81, p<0.0001). Similarly, the time to lactate measurement decreased from 64 minutes to 54.5 minutes (p=0.0117) and the proportion of cases where lactate was measured improved from 64% to 92.3% (p=0.0005). Blood culture rates improved from 79.1% to 100%.

Conclusion

The implementation of the Sepsis Pathway improved time taken to perform investigations and manage patients with sepsis. Although it had improved, there was still a delay in recognition of sepsis and initiation of investigations and management, demonstrating that further strategies need to be employed to reduce poor outcomes associated with sepsis. However, it did not affect ICU admissions, length of stay or mortality.

Author Information

Pourya Pouryahya, Casey Hospital, Emergency Department, Programme of Emergency Medicine, Monash Health, Victoria; Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria; Natalie Guiney, Bendigo Health, Victoria; Alastair Meyer, Casey Hospital, Emergency Department, Programme of Emergency Medicine, Monash Health, Victoria; Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria; Neil Goldie, Monash Emergency Research Collaborative, School of Clinical Sciences, Monash Health, Monash University, Victoria; Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria.

Acknowledgements

Special thanks to all Casey Hospital emergency department team and Monash Health sepsis group for their support during this study.

Correspondence

Dr Pourya Pouryahya, Casey Hospital, 62 Kangan Drive, Berwick, Victoria 3806.

Correspondence Email

pourya.pouryahya@monashhealth.org

Competing Interests

Nil.

1. Damiani E, Donati A, Serafini G, Rinaldi L, Adrario E, Pelaia P, et al. Effect of Performance Improvement Programs on Compliance with Sepsis Bundles and Mortality: A Systematic Review and Meta-Analysis of Observational Studies. PLOS ONE. 2015; 10(5):e0125827.

2. Levy M, Dellinger R, Townsend S, Linde-Zwirble W, Marshall J, Bion J, et al. The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Critical Care Medicine. 2010; 38(2):367–374.

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