Monitoring of Perfusion in Sepsis and Malaria

Summary

Sepsis and severe malaria together contribute to an estimated 13 million deaths annually, a great burden of which is in low-income countries. Optimal fluid management is critical yet remains one of the most challenging clinical care elements as volume overload precipitates pulmonary edema and volume restriction may exacerbate acute kidney injury. These complications of sepsis and severe malaria significantly increase mortality, particularly in resource-limited settings lacking mechanical ventilation and renal replacement therapy. Point-of-care ultrasound and passive leg raise testing are two easily implementable, safe and non-invasive clinical bedside fluid assessment tools that could be applied towards developing a fluid management algorithm in low resource settings. Similarly, simple tissue perfusion measures can facilitate understanding of precise indications or contraindication to fluid and vasopressor therapy.

However, the performance of these tools has yet to be confirmed in these settings. Accurate assessment of pulmonary tolerance and fluid responsive patients could aid to tailor vasopressor and fluid therapy to the patient condition and disease phase, thus preventing or detecting iatrogenic pulmonary edema and other pulmonary complications. As there is currently limited evidence supporting fluid management recommendations for severe malaria and sepsis in low-resource settings, the potential application of these management tools could optimize supportive therapy and improve outcomes in these populations.

The main activity proposed is a prospective, observational study of patients with sepsis and severe malaria to describe the relationship between fluid therapy and vasopressor therapy against measures of tissue perfusion and pulmonary congestion in adult patients with severe malaria or severe sepsis. In addition, the study will assess the performance of simple bedside clinical tools assessing fluid responsiveness, pulmonary congestion and peripheral tissue perfusion.

The data from this observational study will facilitate the preparation of a follow-up study to test a clinical algorithm to guide individualized fluid and vasopressor administration.

Conditions

• Severe Sepsis
• Malaria

Interventions

PROCEDURE

Lung Ultrasound examination

Use of lung ultrasound to detect pulmonary complications

PROCEDURE

Compression ultrasonography (CUS)

CUS is a highly sensitive and specific modality used to recognize lower extremity deep venous thrombosis (DVT)

PROCEDURE

Echocardiography

Echocardiogram can be (i) identify imminent life-threatening causes of hemodynamic failure, (ii) recognize coexisting diagnoses that complicate management, (iii) follow the evolution of the disease process, and (iv) monitor response to treatment

PROCEDURE

Inferior Vena Cava ultrasound

Measurement of the inferior vena cava diameter

PROCEDURE

Passive leg raising test (PLR)

Baseline assessment (including pulse rate, systolic and diastolic blood pressure, velocity time integral (VTI) and stroke volume (SV) echocardiographic measurements) will be performed in the resting semi-recumbent position, defined as a position with the trunk elevated 30° to 45° relative to the lower limbs.

PROCEDURE

Orthogonal polarization spectral imaging (OPS)

Measurement of capillary flow in the rectal microcirculation

PROCEDURE

Urine collection (Foley catheter)

For urinalysis, biochemistry, urine microscopy, pH, and culture.

PROCEDURE

Venous blood samplings

for: parasitological and microbiological diagnostics, complete blood count, biochemistry, red cell deformability analyzed by laser assisted rotational cell analyser (LORCA), markers of oxidative stress (peripheral intravenous catheter)

PROCEDURE

Electrocardiogram

all patients will have an ECG performed on enrolment as a non-invasive investigation

PROCEDURE

GlycoCheck

GlycoCheck is a clinical sublingual handheld, bedside microscope that detects erythrocytes within the small sublingual blood vessels measuring 5 to 25 micrometers in diameter. The sublingual vasculature is a validated site for measuring thickness of the endothelial glycocalyx.

Sponsors & Collaborators

• Mahidol Oxford Tropical Medicine Research Unit

  collaborator OTHER

• University of Amsterdam

  collaborator OTHER

• University of British Columbia

  collaborator OTHER

• Chittagong Medical College and Hospital

  collaborator OTHER

• Malaria Research Group & Dev Care Foundation, Dhaka, Bangladesh

  collaborator UNKNOWN

• Beth Israel Deaconess Medical Center

  collaborator OTHER

• University of Oxford

  lead OTHER

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-06-04

Primary Completion

2019-08-29

Completion

2019-09-26

Countries

• Bangladesh

Study Locations