Renin as a Biomarker of Haemodynamic Normalisation

Study design Observational, single centre, prospective cohort study Planned sample size 100 participants

Inclusion criteria The study will evaluate a cohort of participants meeting the following inclusion criteria:

1. admission to the Intensive Care Unit (ICU) after elective and emergency cardiac surgery using cardiopulmonary bypass
2. age 18 years and above
3. arterial, central venous and pulmonary arterial catheters have been inserted as part of routine care Study procedures In addition to routine clinical postoperative data and blood collection, serum renin levels will be analysed on admission, 6 and 24 hours after admission to ICU Study duration 6 months

The renin-angiotensin aldosterone system (RAAS) is integral to cardiovascular homeostasis and involved in the regulation of blood pressure, electrolyte balance and intravascular volume. Renin is produced from the renal juxtaglomerular cells and converts angiotensinogen to angiotensin. Angiotensin is subsequently converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II also promotes the release of aldosterone.The RAAS has an important role in hypotension to retain water through aldosterone and increase systemic vascular resistance mainly through angiotensin II but also through the release of vasopressin.

The RAAS can become dysregulated in critically ill shocked patients. In states such as septic shock the effects of the RAAS are antagonized through the production of vasodilators such a nitric oxide and both angiotensin I and angiotensin II receptors are down regulated. Activation of angiotensin I receptors may furthermore result in the production of pro-inflammatory cytokines that results in further vasodilation and contributes to cardiovascular compromise.

While the RAAS has been extensively investigated in cardiovascular patients there is a paucity of studies relevant to ICU. A recent study suggested that raised serum renin levels in patients with sepsis is associated with acute renal failure. Another study of a small heterogeneous cohort of critically ill patients compared renin to lactate as marker of tissue perfusion.

As RAAS is closely related to the volume state, there is a physiological rationale to investigate serum renin levels together with variables to monitor the intravascular volume, including assessment of the mean systemic filling pressure (Pmsf). An analogue of the Pmsf will be calculated in this study based on routine postoperative haemodynamic monitoring (mean arterial pressure, MAP, central venous pressure, CVP, cardiac output, CO).

Furthermore, there is no current research which looks at serum renin as marker of hemodynamic normalization or association with outcomes after cardiac surgery which is the main purpose of this study.

Serum renin as a candidate sensitive biomarker of hemodynamic homeostasis will be compared to current clinical markers of resuscitation and perfusion including cardiac index, mixed venous oxygen saturation, lactate and venoarterial carbon dioxide gradients.

If the serum renin concentration is found to be a marker of resuscitation and hemodynamic status, the study will examine any associations with lack of hemodynamic normalization and morbidity in cardiothoracic patients. A pragmatic, composite morbidity outcome at 30 days will be used as the primary endpoint. This includes renal impairment, myocardial infarction, persistent cardiogenic shock, arrythmia, respiratory failure, delirium and stroke. An exploratory, secondary outcome will focus on whether serum renin concentrations are associated with acute kidney injury and the need of renal replacement therapy in post cardiac surgical patients.

Eligibility Criteria:
Inclusion Criteria:

1. Admission to ICU after elective and emergency cardiac surgery following cardiopulmonary bypass
2. Age 18 years and above
3. Arterial, central venous catheters and pulmonary arterial catheters are inserted preoperatively

Exclusion Criteria:

1. Age under 18 years
2. Known pregnancy
3. Arterial, central venous catheters and pulmonary arterial catheters that are not indicated as part of routine care
4. End stage renal disease requiring renal replacement therapy
5. Participants with known Child Pugh A cirrhosis or greater
6. Treatment with any steroids
7. Participant is not expected to live beyond the day after the day of admission