Perfusion and Lung Congestion Evaluation Related to Fluids and Vasopressors in Sepsis and Malaria. (PERFuSE): an Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 1
- 主要终点
- Fluid balance volume at 24 hours
研究概览
简要总结
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.
详细描述
This will be a single center, prospective, longitudinal, observational study of patients with sepsis or severe malaria. It is planned that this initial observational study will inform a follow-up intervention study, based on the observational study findings (Lung Ultrasound and Passive Leg Raising- guided Vasopressors and Fluid Management in Patients with Sepsis and Severe Malaria). The follow-up study will propose testing of a clinical algorithm to individualize titration of vasopressors, diuretics and fluids based on the simple tools evaluated during the observational study.
The expected duration of study patient participation is 30 days. Patients will be assessed every 6 hours until fever clearance, parasite clearance (in malaria patients) and GCS normalization (score of 15) on two consecutive assessments. Thereafter, patients will be assessed daily until discharge or death with one follow-up visit at 14 days and a follow-up call at day 30. The prospective, observational recruitment phase of the study is expected to last 15 months.
Funder: Wellcome Trust of Great Britain, Grant reference number: 220211/A/20/Z
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •I. Sepsis criteria:
- •The sepsis criteria include the severe sepsis and septic shock categories according to 2012 Surviving Sepsis Campaign guidelines. Due to a possible delay in obtaining all the enrolment sequential organ failure assessment (SOFA) score variables necessary to fulfil the criteria for the latest 2016 sepsis definition, the 2012 Surviving Sepsis Campaign criteria and the quick SOFA tool will be used for inclusion. However, after study completion, when all admission SOFA scores will be available, all patients will be re-scored according to the Sepsis 3 definition.
- •Inclusion criteria for sepsis:
- •Documented or suspected infection
- •Systolic blood pressure ≤ 100 mmHg, or receiving vasopressor (epinephrine, norepinephrine, dopamine)
- •PLUS one or more of the following:
- •A. Respiratory rate ≥22 breaths per minute or under oxygen therapy or mechanical ventilation B. Altered mental status (Glasgow Coma Scale ≤ 14)
- •Fully informed written consent obtained, including written informed consent from a relative or parent/guardian in case of reduced consciousness and/or age < 16 years.
- •Age ≥12 years
- •Negative peripheral blood slide for any stages of malaria parasites and a negative rapid diagnostic test (RDT) for falciparum and vivax malaria.
- •Within 24 hours of hospital or ICU admission
- •Note: Positive blood or urine cultures not required as eligibility criteria due to limited microbiology laboratory availability.
- •II. Severe malaria criteria Using modified World Health Organization criteria for severe falciparum malaria, as defined previously.
- •Any P. falciparum or P. vivax parasitaemia in adults, detected by asexual stages on a peripheral blood- slide or a positive RDT in combination with one or more:
- •i. GCS <11 ii. Hematocrit < 20% with parasite count >100,000/mm3 iii. Jaundice with parasite count >100,000/mm3 iv. Serum creatinine >3 mg/dL (or anuria) v. Hypoglycemia with venous glucose <40 mg/dL vi. Systolic blood pressure <80 mmHg with cool extremities vii. Peripheral asexual stage parasitemia >10 % viii. Peripheral venous lactate >4 mmol/L ix. Peripheral venous bicarbonate <15 mmol/L x. Respiratory distress/pulmonary edema: radiologically confirmed, or oxygen saturation <92% on room air with a respiratory rate >30/min, often with chest indrawing and crepitations on auscultation xi. Spontaneous bleeding xii. Generalized convulsions (≥2 in 24 hours)
- •Fully informed written consent obtained, including written informed consent from relative or parent/guardian in case of reduced consciousness and/or age < 16 years.
- •Age ≥12 years
- •Within 24 hours of antimalarial treatment
- •III. Uncomplicated malaria criteria (control group)
- •P. falciparum slide positive (asexual stages) on peripheral blood slide or positive RDT in combination with none of the above severity criteria.
- •Within 24 hours of start of antimalarial treatment
- •Fully informed written consent obtained, including written informed consent from relative or parent/guardian in case of reduced consciousness and/or age < 16 years.
- •Age ≥12 years
- •Exclusion Criteria
- •The participant may not enter the study if ANY of the following apply:
- •Patients admitted with known malignancy or liver disease
- •Recent surgery (as part of current admission)
- •Trauma (resulting in current admission)
- •Antimalarial treatment ≥24 hours prior to screening
排除标准
- 未提供
结局指标
主要结局
Fluid balance volume at 24 hours
时间窗: On the first 24 hours from enrollment
Fluid balance volume in milliliters calculated daily as inputs minus outputs.
Vasopressor therapy
时间窗: 72 hours
Expressed as dichotomous variable, use of any vasopressor during the first 72 hours.
Global ultrasound aeration score
时间窗: 72 hours
The score ( range 0-36) is calculated over 12 lung zones where each zone is scored 0 to 3.
Plasma lactate levels
时间窗: 72 hours
Plasma venous lactate levels expressed in mmol/L
Fluid balance volume at 48 hours
时间窗: On the first 48 hours from enrollment
Fluid balance volume in milliliters calculated daily as inputs minus outputs.
Fluid balance volume at 72 hours
时间窗: On the first 72 hours from enrollment
Fluid balance volume in milliliters calculated daily as inputs minus outputs.
次要结局
- Core-periphery temperature gradient(°C)(72 hours)
- Case fatality in first 30 days.(30 days)
- Microbiological etiology of sepsis.(72 hours)
- Number of patients with ARDS according to the Kigali Modification of the Berlin Definition of ARDS(72 hours)
- Proportion of patients with microvasculature obstruction or abnormalities(24 hours)
- Proportion of patients that develop lower extremity deep venous thrombosis.(72 hours)
- Plasma creatinine levels(48 hours)
- The ratio between pulse oxymetry hemoglobin saturation and the fraction of inspired oxygen (SpO2/FiO2 ratio).(72 hours)
- Positive chest X-ray for pulmonary edema (dichotomous variable)(72 hours)
- Prolonged capillary refill time (dichotomous variable, defined as ≥3 seconds)(72 hours)
- Cardiac index (in liters per minute per square meter of body surface area)(72 hours)
- Proportion of patients at enrolment and during admission with a low cardiac index and hypoperfusion state.(72 hours)
- Proportion of patients that develop pulmonary edema and acute respiratory distress syndrome (ARDS).(72 hours)
- Proportion of fluid responsive patients(72 hours)
- Skin mottling score (0-5)(72 hours)
- Acute kidney injury (AKI)(At admission, up to day 14, and renal recovery by 30 days)
- Diagnostic performance measures (sensitivity, specificity, positive predictive value, negative predictive value) of the digital microscope with expert microscopy as the gold standard(7 days)