ORIGINAL ARTICLE Year : 2023  |  Volume : 30  |  Issue : 1  |  Page : 70-74

Utility and impact of early diagnostic assessment of sepsis on mortality in an emergency department of a tertiary hospital in Lagos, Nigeria

Iorhen Ephraim Akase1, Henry Chukuma Akujobi2, Oziegbe Oghide2, Akinsanya Daniel Olusegun-Joseph3, Chukwuemeka Abraham Agbarakwe2, Adefolarin Opawoye4
1 Infectious Diseases Unit, Department of Medicine, College of Medicine, University of Lagos; Department of Medicine, Lagos University Teaching Hospital, Lagos, Nigeria
2 Accident and Emergency Department, Lagos University Teaching Hospital, Lagos, Nigeria
3 Department of Medicine, Lagos University Teaching Hospital; Cardiology Unit, Department of Medicine, College of Medicine, University of Lagos, Lagos, Nigeria
4 Department of Medicine, Lagos University Teaching Hospital, Lagos, Nigeria, Lagos, Nigeria

Date of Submission09-Jul-2022Date of Decision14-Sep-2022Date of Acceptance02-Jan-2023Date of Web Publication09-Feb-2023

Correspondence Address:
Iorhen Ephraim Akase
Infectious Diseases Unit, Department of Medicine, College of Medicine, University of Lagos, Lagos
Nigeria

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/npmj.npmj_190_22

Context: Currently, little is known about the timely application of clinical screening tools and blood sampling for decision-making in the management of patients with suspected sepsis in the accident and emergency units of hospitals in Nigeria. Aim: The aim of the study was to ascertain the association between the time taken for the conduct of serum lactate and blood culture investigations following a clinical suspicion of sepsis, and the mortality of patients admitted to a Nigerian tertiary hospital. Methods: Over a 6-month period (November 2021 to April 2022), 119 patients hospitalised for sepsis or septic shock at the Lagos University Teaching Hospital were followed until discharge or death. The proportion of patients whose serum lactate, serum procalcitonin and blood culture samples was taken was also determined. Predictors of mortality were determined using bivariate analysis and logistic regression. Kaplan–Meier plots were used to predict survival using sepsis diagnostic criteria. Results: Eighty (67%) of 119 sepsis patients met systemic inflammatory response syndrome or quick sequential (sepsis-related) organ failure assessment criteria. Only 3 (2.5%) patients had blood cultures and serum procalcitonin and 0 (0%) had serum lactate tests. Forty-one (34.5%) patients died, but clinical and laboratory procedures for sepsis management were not linked to death. A shorter hospital stay increased the death risk (χ2 = 14.83, P = 0.002). Conclusion: This study revealed low compliance with sepsis care guidelines and no impact of timely clinical and laboratory procedures on sepsis mortalities. Further study is needed to explore patient care models that can improve the objective assessment and treatment of sepsis patients in emergency departments of busy tertiary hospitals.

Keywords: Accident and emergency department, sepsis mortality, tertiary hospital, timeliness of assessment

How to cite this article:
Akase IE, Akujobi HC, Oghide O, Olusegun-Joseph AD, Agbarakwe CA, Opawoye A. Utility and impact of early diagnostic assessment of sepsis on mortality in an emergency department of a tertiary hospital in Lagos, Nigeria. Niger Postgrad Med J 2023;30:70-4
How to cite this URL:
Akase IE, Akujobi HC, Oghide O, Olusegun-Joseph AD, Agbarakwe CA, Opawoye A. Utility and impact of early diagnostic assessment of sepsis on mortality in an emergency department of a tertiary hospital in Lagos, Nigeria. Niger Postgrad Med J [serial online] 2023 [cited 2023 Feb 9];30:70-4. Available from: https://www.npmj.org/text.asp?2023/30/1/70/369303   Introduction 

Sepsis is associated with high morbidity and mortality.[1] It is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[2] Estimates of cases of sepsis in the United States, the United Kingdom and Europe range between 0.4/1000 and 1/1000.[3] It is one of the most common reasons for admission in a medical emergency and accounts for an estimated 10% of intensive care unit admissions.[4] The incidence of sepsis has been increasing over the last few decades, partly due to increasing age and life expectancy, an increase in comorbidities and the increasing availability of immunosuppressive and invasive treatments.[3],[4] The cases of death from sepsis have, however, reduced from 35% to 18% in the last 20 years due to improvements in early detection and supportive care.[4] Associated cost of management is, however, high, as high as over $20 billion annually in the United States.[3]

In resource-limited settings like Nigeria, morbidity and mortality associated with sepsis are still high. A study conducted in two tertiary hospitals in South-East Nigeria revealed an incidence of 7.41% amongst medical admissions.[5] An audit of sepsis patients in North Central Nigeria found a mortality rate of 53% amongst patients admitted with sepsis over a 14-month period.[6]

Early recognition of sepsis is enhanced through the judicious use of the sequential (sepsis-related) organ failure assessment (SOFA). Patients with sepsis are identified by a score of ≥2 points.[2] The use of this scoring index in the accident and emergency (A&E) department is often hampered by collateral requirements for laboratory assessments and the demonstration of organ dysfunction using critical care assessments.[2],[7] The development of the quick SOFA (qSOFA) score was an attempt to overcome the challenges associated with the use of the SOFA, as it requires only clinical parameters such as respiratory rate, blood pressure and Glascow coma score (GCS).[2] As a result, qSOFA is easily applicable in the emergency room, with a qSOFA score of ≥2 points displaying a high degree of sensitivity in identifying patients with a greater risk of sepsis-related worsening and adverse outcomes.[2]

In most resource-constrained settings, however, the older systemic inflammatory response syndrome (SIRS) score is more widely used for identifying patients with sepsis, due to its higher sensitivity.[7] In patients who meet the qSOFA and/or SIRS criteria, the Surviving Sepsis Campaign (SSC) recommendations indicate that blood cultures and serum lactate be conducted, as well as the administration of appropriate antibiotics, within 1 h of the clinical diagnosis of sepsis.[8]

In Nigeria, therapeutic decisions for sepsis management are often delayed and antibiotic prescriptions are inappropriate.[5],[6] Up to 33.8% of patients initially diagnosed clinically with sepsis did not ultimately meet the diagnostic criteria for sepsis, 24.5% of antibiotics prescribed for the management of sepsis were inappropriate and antibiotics were not administered within the first hour as required.[5] A cross-sectional online survey of 25 public secondary health-care facilities in Abuja, Federal Capital Territory, and Lagos State, Nigeria, revealed that only 2.7% of sepsis cases had routine blood culture testing and only 32% (8/25) of facilities reported performing blood cultures.[9] Currently, little is known about the timely application of clinical screening tools and blood sampling for decision-making on the management of patients with suspected sepsis in the A&E units of hospitals in Nigeria.

The aim of the study was to ascertain the association between the time taken for the conduct of serum lactate and blood culture investigations following a clinical suspicion of sepsis and the mortality of patients admitted to a Nigerian tertiary hospital.

  Methods 

Study design and study setting

This study was a cohort study. All patients admitted in the A&E Department of Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, with a working diagnosis of sepsis or septic shock by the managing clinicians were enrolled into the study. Patients admitted to the LUTH emergency department with a diagnosis of sepsis and older than 18 years of age were recruited sequentially until the minimum sample size was reached. Recruited patients were followed up till discharge from the hospital or death. The recruitment period lasted from November 2021 to April 2022. Written consent was obtained from patients or from the next of kin for those too ill to provide consent.

The study was approved by the Health Research Ethics Committee (HREC) of LUTH, Idi-Araba, with approval number ADM/DSCST/HREC/APP/2642, initially given 05 November 2018, and extended from 16 November 2021 to 16 November 2022.

Sample size

The sample size was calculated using the formula by Daniel:[10] , with the standard normal deviate at 5% type 1 error, a precision/absolute error of 5% and a 7.4% incidence of sepsis on admissions.

Minimum required sample size required = 105.30. Using an attrition rate of 10% (i.e. 11 patients), a sample size of 119 patients was recruited for this study.

Study procedure

For this study, sepsis was defined using the SIRS and/or qSOFA criteria. The SIRS criteria define sepsis as 'suspected infection in the presence of two SIRS signs: tachycardia (heart rate >90 beats/min), tachypnoea (respiratory rate >20 breaths/min), fever or hypothermia (temperature >38°C or <36°C) and leucocytosis (white blood cells >11,000/mm3), leucopenia (white blood cells <4000/mm3) or bandemia (band forms ≥10%)'. A score of ≥2 is indicative of suspected sepsis in the presence of suspected or proven infection.[9] The sepsis-3 criteria utilises the qSOFA score which assigns one point to each of the following three criteria: (1) respiratory rate ≥22 cycles/min, (2) altered mental status or (3) systolic blood pressure ≤100 mmHg. A score of ≥2 in a patient with suspected infection indicates a greater risk of death.

Study procedure

Clinical and laboratory evaluation

Information on the patient's age and sex was collected. Each patient's temperature was taken, and a decision about if the patient had fever or hypothermia was made using axillary temperature measurement. A patient was classified as having a fever if the axillary temperature was >37.3°C and hypothermia if the temperature was below 36°C.[11]

In addition, the respiratory rate, pulse rate and blood pressure, of all patients were documented at admission and 30 min after the presentation. The two readings were used to categorise the patients as having sepsis or not. Patients who were catheterised and those who received intravenous fluids were noted. In addition, the GCS score on admission was documented.

Subsequently, the temperature, oxygen saturation, respiratory rate, pulse rate, blood pressure and GCS score of all patients were documented every 6 h. All patients were closely observed until they were discharged or died.

Laboratory assessment

Following the clinical evaluation on admission, patients are required to have blood samples taken for serum lactate, serum procalcitonin and blood culture within 1 h of presentation was recorded. These tests were performed as part of standard care for sepsis patients admitted to the A&E department. The investigations requested and the time of sample collection for such investigations was documented.

Data analysis

Data were cleaned and analysed using the STATA, Version 13 (StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX, USA: StataCorp LP). Bivariate analysis and logistic regression were conducted to determine the predictors of mortality. The regression model was done with the 'best fit' option of including covariates, and the model was checked for fit using the Hosmer–Lemeshow goodness-of-fit test. The duration of admission was in days, but it was log-transformed for the regression analysis. Additional analysis using the data as survival data was done to plot Kaplan–Meier curves and determine the survival function using the sepsis diagnostic criteria as predictors. The threshold for statistical significance was set at 0.05.

  Results 

The treating physicians admitted 119 individuals with a clinical suspicion of sepsis. These patients all consented to be enrolled into the study. The median age of the participants was 44 years (interquartile range [IQR]: 32 years). There was an almost equal male-to-female distribution of participants (50.8% vs. 49.2%).

Proportion of admitted patients that fulfilled criteria for sepsis

Eighty (67.2%) of the 119 hospitalised patients fulfilled either SIRS or qSOFA clinical criteria for sepsis. More patients with sepsis were picked by the SIRS criteria than the qSOFA criteria (60.5% vs. 29.4%).

The level of compliance with the recommended standard of care

[Table 1] shows the proportion of recruited participants who received the recommended resuscitative and diagnostic measures according to the SSC guidelines. Serum lactate was not available to guide the care of any of the patients.

Table 1: The proportion of sepsis patients that underwent clinical and diagnostic procedures within 1 h of admission

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The outcome of patients with sepsis

Forty-one of (34.5%) participants died while on admission. The median duration of admission was 7 days (IQR: 9 days). There was no significant association between the timeliness to the conduct of the clinical or diagnostic procedures at the A&E room and death [Table 2]. However, a shorter duration on admission was associated with a higher risk of death, with the chance of dying reducing as the period of admission increases after adjusting for age, sex and sepsis diagnosis and management compliance measures [Table 3]. Even though those diagnosed with sepsis using both criteria died sooner, the survival function did not differ significantly based on diagnostic criteria (P = 0.6350), as illustrated in [Figure 1].

Table 2: Association between the timeliness to the conduct of the clinical or diagnostic procedures at the accident and emergency room and death

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Table 3: Effect of age, sex, duration on admission and sepsis diagnosis compliance measures on death

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Figure 1: Survival estimate for all sepsis patients according to diagnostic criteria

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  Discussion 

The study showed that about one-third of the patients admitted with a clinical impression of sepsis did not meet SIRS or qSOFA clinical criteria for sepsis. In addition, compliance with SSC recommendations for intravenous fluids, urinary catheterisation, blood cultures, serum procalcitonin and serum lactate was suboptimal. There was no significant association between the timeliness of the procedures and the outcome of the patients, although a shorter duration of admission was associated with higher risks of death.

Our study found that one-third of patients admitted with a clinical impression of sepsis did not meet either the SIRS or qSOFA criteria for clinical assessment of sepsis, which is similar to the findings of a previous study conducted in Nigeria, which found that 33.8% of patients with a presumptive diagnosis did not meet clinical criteria.[6] This finding suggests that neither the SIRS nor qSOFA criteria were employed for sepsis triage in the emergency unit of this tertiary health institution. Rather, it is possible that the A&E clinicians make diagnoses of sepsis subjectively. The risk is the misdiagnosis of infections that do not lead to sepsis or organ failure caused by non-infectious causes as sepsis; and the failure of identifying patients with sepsis. A lack of user-friendly work aids and standard operating procedures that guide doctors on how to utilise clinical tools for sepsis diagnosis may have led to this predicament. This highlights the importance of providing easy-to-use aids in A&E departments to facilitate prompt decision-making, assist providers in recalling correct use instructions and promote conformity with global and national sepsis treatment guidelines.

The sensitivity of SIRS and qSOFA criteria in detecting sepsis in this study cohort is similar to the result from Australia that showed that qSOFA criteria are specific for predicting sepsis but have low sensitivity.[11] This is in contrast to the SIRS criteria that is highly sensitive for predicting sepsis but not very specific.[2] There have been discussions on the efficacy of either SIRS or qSOFA criteria in low-resource settings, with suggestions that there may be a need to develop context-specific criteria for sepsis detection.[7] It is believed that the South African Triage Score is better suitable for Africa, but additional validation is required before it can be extensively used in Africa.[12],[13]

The low level of adherence to the SSC recommendations is consistent with what has been observed in Nigeria, where 2.7% (80/2924) of patients had blood cultures requested,[9] and South Africa, where 379/677 patients (56%), complied with all metrics in the 3-h SSC bundle.[14] Compliance with SSC guidelines improves outcomes in China, Europe and the USA.[15],[16],[17] Compliance with the SSC guidelines in many Sub-Saharan countries has shown conflicting relationships between compliance and mortality from sepsis,[14],[18],[19] possibly due to underlying immunosuppression from malnutrition and chronic infections such as tuberculosis, HIV and helminthic infections.[19] Low compliance with SSC guidelines is common in low-resource settings.[3],[20] This may be because of procedural delays in accessing materials for sample collection, the difficulty patients face in paying for services, the over-burdened staff who are not able to keep up quality care delivery for the high patient load they manage, poor understanding of the standard operating procedures for the care of patients with sepsis and poorly trained laboratory personnel to handle the required investigations.[9],[20] This requires an immediate examination of the systems inside the A&E department, as well as enhanced logistical and laboratory assistance. In addition, the provision of navigational aids for patients has been demonstrated to enhance patient care turnaround times in crowded emergency departments.[21]

Our study did not find any significant association between the timeliness to procedures and the mortality of the patients admitted, a result similar to that reported in South Africa.[14] However, only a small proportion of patients in our cohort had their samples taken for blood cultures, serum lactate and serum procalcitonin testing. Due to variations in host characteristics, causative organisms, clinical settings and resources, it has been hypothesised that the association between the timeliness of resuscitative and diagnostic therapies and mortality may be different in Africa compared to high-income settings.[20] This postulation needs to be investigated further.

The finding of our study that a longer hospital stay for sepsis patients was associated with a lower risk of mortality has been replicated in a number of countries.[22],[23],[24] Early mortality in patients with sepsis is most likely a reflection of the severity of organ dysfunction at presentation[23] and the absence or delay in early resuscitative measures to support organ function.[24] The reduction in mortality seen in other studies amongst sepsis patients is unmistakably linked to prompt, aggressive organ support and timely intervention.[2],[3],[4] This emphasises the significance of prompt, early resuscitative measures to support organ function in patients with sepsis. Patients presenting with any kind of emergency are more likely to die prematurely if they get insufficient basic organ support and endure logistical delays, both of which are prevalent in low-resource countries like Nigeria.[25]

The main strength of our study was the observational cohort study design, which allowed us to ascertain the admission parameters and to ascertain the timeliness of the procedures conducted. Another strength is that we were able to provide the first set of baseline data on the level of compliance of admitting physicians to diagnostic criteria and initial resuscitative procedures when managing patients with sepsis in Nigeria. In addition, this data generated from the A&E of the largest tertiary hospital in the most populous city in Nigeria provides a window through which we can view the challenges bedevilling most tertiary health facilities in Nigeria.

The current study is, however, limited by our inability to capture data on the pre-hospital care received by patients before admission at the A&E. This information may have had an impact on the clinical presentations and outcomes. Furthermore, we did not have data on other factors that could significantly affect the outcome of the patients such as the presence of comorbidities and the socioeconomic status of the participants. Despite these study limitations, the study findings provide important information that can help improve the management of sepsis in tertiary health institutions in Nigeria.

  Conclusion 

This study demonstrated the low use of serum lactate and blood culture for the diagnosis of sepsis in the emergency department of a tertiary health facility in Nigeria. There was also no association between the clinical and diagnostic procedure timeliness and patients' survival. These findings highlight the increased risk of poor quality care for sepsis patients, as well as the risk of misdiagnosing patients with sepsis. Further studies are required to identify patient care models that can support staff at the A&E units of busy tertiary health institutions to improve on the objective assessment and care of patients with sepsis, though we could not demonstrate that this reduces the risk of death of patients.

Acknowledgements

We thank Prof. MO Ukpong and Prof. NU Okubadejo for their guidance and comments that greatly improved the manuscript. We also thank our colleagues (doctors, nurses and support staff) from the triage and medical emergency unit of LUTH Accident and Emergency, who were involved in the care of the patients during admission and whose records have been used for the research.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

  References 
1.Cuthbertson BH, Elders A, Hall S, Taylor J, MacLennan G, Mackirdy F, et al. Mortality and quality of life in the five years after severe sepsis. Crit Care 2013;17:R70.  
    2.Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801-10.  
    3.Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing sepsis as a global health priority – A WHO resolution. N Engl J Med 2017;377:414-7.  
    4.Moss M, Martin GS. A global perspective on the epidemiology of sepsis. Intensive Care Med 2004;30:527-9.  
    5.Iroezindu MO, Isiguzo GC, Unigwe US, Onodugo OD, Isa SE, Daniyam CA, et al. Epidemiology and predictors of mortality among sepsis patients in South East Nigeria. Am J Respir Crit Care Med 2017;195:A5026.  
    6.Isa SE, Iroezindu MO, Awang SK, Simji GS, Onyedibe KI, Egah DZ, et al. An audit of diagnosis and treatment of sepsis in north-central Nigeria. Niger J Med 2013;22:319-25.  
  [Full text]  7.Keeley AJ, Nsutebu E. Improving sepsis care in Africa: An opportunity for change? Pan Afr Med J 2021;40:204.  
    8.Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021;47:1181-247.  
    9.Egwuenu A, Ejikeme A, Tomczyk S, Von-Laer A, Ayobami O, Odebajo O, et al. Baseline study for improving diagnostic stewardship at secondary health care facilities in Nigeria. Antimicrob Resist Infect Control 2022;11:1-0.  
    10.Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med 2013;35:121-6.  
[PUBMED]  [Full text]  11.Williams JM, Greenslade JH, McKenzie JV, Chu K, Brown AF, Lipman J. Systemic inflammatory response syndrome, quick sequential organ function assessment, and Organ dysfunction: Insights from a prospective database of ED patients with infection. Chest 2017;151:586-96.  
    12.Soogun S, Naidoo M, Naidoo K. An evaluation of the use of the South African triage scale in an Urban district hospital in Durban, South Africa. S Afr Fam Pract 2017;59:133-7.  
    13.Rominski S, Bell SA, Oduro G, Ampong P, Oteng R, Donkor P. The implementation of the South African Triage Score (SATS) in an urban teaching hospital, Ghana. Afr J Emerg Med 2014;4:71-5.  
    14.Green S, Smith MT, Kong VY, Skinner DL, Bruce JL, Laing GL, et al. Compliance with the surviving sepsis campaign guidelines for early resuscitation does not translate into improved outcomes in patients with surgical sepsis in South Africa. S Afr J Surg 2019;57:8-12.  
    15.Chen H, Zhao C, Wei Y, Jin J. Early lactate measurement is associated with better outcomes in septic patients with an elevated serum lactate level. Crit Care 2019;23:351.  
    16.Moore WR, Vermuelen A, Taylor R, Kihara D, Wahome E. Improving 3-hour sepsis bundled care outcomes: Implementation of a nurse-driven sepsis protocol in the emergency department. J Emerg Nurs 2019;45:690-8.  
    17.Delawder JM, Hulton L. an interdisciplinary code sepsis team to improve sepsis-bundle compliance: A quality improvement project. J Emerg Nurs 2020;46:91-8.  
    18.Asiimwe SB, Okello S, Moore CC. Frequency of vital signs monitoring and its association with mortality among adults with severe sepsis admitted to a general medical ward in Uganda. PLoS One 2014;9:e89879.  
    19.Jacob ST, Banura P, Baeten JM, Moore CC, Meya D, Nakiyingi L, et al. The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: A prospective intervention study*. Crit Care Med 2012;40:2050-8.  
    20.Rudd KE, Kissoon N, Limmathurotsakul D, Bory S, Mutahunga B, Seymour CW, et al. The global burden of sepsis: Barriers and potential solutions. Crit Care 2018;22:232.  
    21.Bischof JJ, Sellers JB, Phillips AW, Petrongelli JJ, Stuckey AE, Platts-Mills TF. Patient navigation for complex care patients in the emergency department: A survey of oncology patient navigators. Support Care Cancer 2019;27:4359-62.  
    22.Karakike E, Giamarellos-Bourboulis EJ. Macrophage activation-like syndrome: A distinct entity leading to early death in sepsis. Front Immunol 2019;10:55.  
    23.Javed A, Guirgis FW, Sterling SA, Puskarich MA, Bowman J, Robinson T, et al. Clinical predictors of early death from sepsis. J Crit Care 2017;42:30-4.  
    24.Rhodes A, Phillips G, Beale R, Cecconi M, Chiche JD, De Backer D, et al. The surviving sepsis campaign bundles and outcome: Results from the international multicentre prevalence study on sepsis (the IMPreSS study). Intensive Care Med 2015;41:1620-8.  
    25.Bernhard M, Becker TK, Nowe T, Mohorovicic M, Sikinger M, Brenner T, et al. Introduction of a treatment algorithm can improve the early management of emergency patients in the resuscitation room. Resuscitation 2007;73:362-73.  
    
  [Figure 1]
 
 
  [Table 1], [Table 2], [Table 3]