Saving Lives by Early Detection and Treatment of Sepsis and Septic Shock by Point of Care Lactate Test in Adults (POCLactate)

Burden:

The global burden of sepsis is difficult to ascertain, although a recent scientific publication estimated that in 2017 there were 48.9 million cases and 11 million sepsis-related deaths worldwide, which accounted for almost 20% of all global deaths. Recent chart analysis from Dhaka Hospital, icddrb recorded 350 adults with severe sepsis admitted over four years. Among them, 69% of patients progressed to septic shock.

Knowledge gap:

Clinical features of shock due to sepsis and shock due to severe dehydration are very intertwining and often predicament for critical care physicians. If not recognized early and managed promptly, it can lead to septic shock, multiple organ failure, and eventually death. Serum lactate may play a role as the point of care test in differentiating shock due to severe sepsis from shock due to severe dehydration.

Relevance:

Being the largest diarrhoeal disease hospital, the Dhaka Hospital of icddr,b is ideal for researching shock with diarrheal diseases. Even though the onset of sepsis can be acute and poses a short-term mortality burden, it can also cause significant long-term morbidity, requiring treatment and support. Thus, addressing sepsis and severe sepsis by early detection and prompt management should be a comprehensive way to reduce the burden in our community.

Study Overview

• Status: Recruiting
• Conditions: Lactate Blood Increase; Severe Sepsis With Septic Shock
• Intervention / Treatment: Diagnostic test: Point of care Lactate

Detailed Description

The global burden of sepsis is difficult to ascertain, although a recent scientific publication estimated that in 2017 there were 48.9 million cases and 11 million sepsis-related deaths worldwide, which accounted for almost 20% of all global deaths. Recent chart analysis from Dhaka Hospital recorded 350 adults with severe sepsis admitted to a diarrheal hospital over four years, among them, 69% of patients progressed to septic shock.

If not recognized early and managed promptly, it can lead to septic shock, multiple organ failure, and death. It is most frequently a serious complication of infection, particularly in low- and middle-income countries. Early diagnosis and timely and appropriate clinical management of sepsis, such as optimal antimicrobial use and fluid resuscitation, are crucial to increase the likelihood of survival. Even though the onset of sepsis can be acute and poses a short-term mortality burden, it can also be the cause of significant long-term morbidity requiring treatment and support. Thus, sepsis requires a multidisciplinary approach.

Shock may occur as a ramification of severe sepsis, and on the other hand, a patient may present with shock due to severe dehydration from severe diarrhea. However, the differentiation of shock as a cascade of severe sepsis from the shock due to severe dehydration is intriguing. Fluid management in these two entities is different, although the initial bolus (30 ml/kg) in both cases is the same. If fluid management could not be done efficiently, some patients might end up with fluid overload especially in case of shock due to severe sepsis and under hydration in case of shock due to severe dehydration. On the other hand, there could be also overuse of inotropes if we are unable to identify the requirement of additional fluid. Thus, we need to have a point of care biomarker that may guide us further fluid requirement (or requirement of inotrope) after the initial bolus. Not only is severe sepsis the most common non-cardiac cause for intensive care unit (ICU) use, it has emerged as a major driver of hospital costs in developing countries.

Serum lactate level, which measures the level of lactic acid in the blood, is a fairly reliable and accurate indication of tissue hypoperfusion and hypoxia. The signs and symptoms, which may vary from patient to patient, include altered mental status; pale, cool, clammy skin; nausea and vomiting; diaphoresis; hypotension; tachypnea; and tachycardia. Surprisingly all these features are evident in severe sepsis or severe dehydration. In addition, septic shock is often associated with macrocirculatory dysfunction causing arterial hypotension, microcirculatory dysfunction, and decreased oxygen and nutrient extraction by peripheral tissues. Thus, lactic acid levels have become a useful marker for tissue hypoperfusion and may also serve as an endpoint for resuscitation in patients with sepsis and septic shock.

Serum lactate is proven to be an ideal point of care test to diagnose severe sepsis or septic shock successfully. On the other hand, although there is very limited knowledge regarding the utility of serum lactate in severe dehydration, evidence showed a reduction of serum lactate level after successful hydration.

Based on this evidence, we aimed to conduct this prospective exploratory study of serum lactate to differentiate severe dehydration from severe sepsis.

Methodology:

Study design: This is an observational exploratory study to find out the role of serum lactate to differentiate patients having shock due to severe sepsis and shock due to severe dehydration.

Primary Objectives:

Role of serum lactate to identify the requirement of inotropes between patients having shock due to severe sepsis and shock due to severe dehydration.

Secondary Objectives:

i) Prognostic accuracy of serum lactate level for mortality outcome among adults with severe sepsis or septic shock.

ii) Prevalence of severe sepsis or septic shock among diarrheal patients.

Study duration:

12 months (Patient enrolment will be continued for completed six months)

Sample Size Calculation This will be an eight months' time-bound study. In the last six months in 2021, we have evaluated 198 patients in our suspected COVID-19 tent, where 78 were suspected of severe sepsis or septic shock. Based on this assumption we expect to enroll consecutive 80 patients, each with severe sepsis and/or shock, and 80 patients with only severe dehydration without any other associated co-morbidities.

Data analysis Data will be analyzed by using SPSS, STATA and Epi info by the investigators and statisticians of icddr,b. The primary endpoint of this trial is the difference of serum lactate levels in shock due to severe sepsis group and shock due to severe dehydration group. For comparison of parametric continuous variable, we will use paired t-test. For non-parametric continuous variable, we will use Mann Whitney U test. For comparison of the dichotomous or categorical variables such as: requirement of multiple inotropes, duration of hospitalization, mortality during hospitalization and bacterial isolation from blood or stool we will use Chi square test and the Fisher's exact test if the expected frequency of any cell is less than 5.

Odds ratio (OR) and their 95% confidence intervals (CIs) were used to demonstrate the strength of association. For statistically significant, a p-value is set <0.05. To identify association of high lactate level with severe sepsis in diarrheal adults, initially, a bivariate model will be built, and then a multivariable regression analysis model identified factors independently associated with severe sepsis after controlling for the relevant confounding variables.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: M.A Salam Khan; Phone Number: 01711428989; Email: salamk@icddrb.org

Study Locations

• Bangladesh
  • Outside U.S. And Canada
    • Dhaka, Outside U.S. And Canada, Bangladesh, 1212
      • Recruiting
      • International Centre for Diarrheal Disease Research, Bangladesh
      • Contact: M.A Salam Khan; Phone Number: 01754598328; Email: salamk@icddrb.org
      • Principal Investigator: Lubaba Shahrin, FCPS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Diarrhea is the entry point for admission to the hospital. Adults presenting with diarrhea and clinically defined and severe sepsis or septic shock recommended by surviving sepsis guidelines supported with our local evidence will be selected as participants in the study. Adults presenting with severe dehydration assessed by the admitting doctor will be enrolled as a comparison group for comparing the role of lactate in both conditions.

Description

Inclusion Criteria:

• Patients have shock due to severe sepsis or septic shock.
• Consent to participate in the study from the patient or his accompanying caregiver.

Exclusion Criteria:

• Any emergency which might require urgent referral within half an hour of admission.
• Known case of cancer or chemotherapy.
• Life-threatening conditions required cardiopulmonary resuscitation (CPR) on arrival.
• Cardiac shock or anaphylactic origin

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case; Severe sepsis with or without shock	Diagnostic test: Point of care Lactate; StatStrip Lactate is a handheld, point-of-care (POC) meter that brings lactate testing directly to the bedside. Lactate measured with blood gas analyzers is problematic for bedside care. Blood gas analyzers require arterial samples, large sample volumes (100-200 μL), and long analysis times (up to 2.5 minutes). In addition, blood gas analyzers are complex to use, stationary, and expensive to purchase and run. StatStrip Lactate testing is as easy as bedside glucose testing. Single-use, pre-calibrated biosensors provide the fastest turnaround time (13 seconds) from the smallest whole blood sample (0.6 μL) with excellent correlation to central laboratory reference methods.
Comparison; Severe dehydration with shock	Diagnostic test: Point of care Lactate; StatStrip Lactate is a handheld, point-of-care (POC) meter that brings lactate testing directly to the bedside. Lactate measured with blood gas analyzers is problematic for bedside care. Blood gas analyzers require arterial samples, large sample volumes (100-200 μL), and long analysis times (up to 2.5 minutes). In addition, blood gas analyzers are complex to use, stationary, and expensive to purchase and run. StatStrip Lactate testing is as easy as bedside glucose testing. Single-use, pre-calibrated biosensors provide the fastest turnaround time (13 seconds) from the smallest whole blood sample (0.6 μL) with excellent correlation to central laboratory reference methods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum lactate level after completion of hydration in the presence of clinical features of severe sepsis and shock	First sample (POC-1): Lactate level on enrolment Second sample (POC-2): Lactate level after fluid bolus Expected outcome: Change in level of POC Lactate will be significant in those who do not require inotropes compared to those who require inotropes.	Within 90 minutes of enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Requirement of multiple inotropes	Through looking at the POC lactate test, prediction of requirement of more than one ionotrops	Within 6 hours of enrollment

Collaborators and Investigators

• Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2021
• Primary Completion (Anticipated): August 31, 2022
• Study Completion (Anticipated): August 31, 2022

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 24, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Adult; Septic Shock; Severe Sepsis; Severe dehydration; POC Lactate
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Shock, Septic; Shock; Hyperlactatemia
• Other Study ID Numbers: PR-21097

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The full data is accessible as per the data sharing policy of icddrb through Research Administration.
• IPD Sharing Time Frame: After the publication of research findings in peer reviewer journal
• IPD Sharing Access Criteria: Communication with the Research Administration of icddrb through the website
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes