Jon Fanning

Optimising intraoperative coagulation management for precision vascular surgery

Overview:

Vascular clamping, interruption of in-line laminar flow and exposure of blood to artificial surfaces, air and prothrombotic layers of the vascular wall all make vascular surgery one of the most prothrombotic settings in medicine, necessitating anticoagulation to avoid thrombotic burden, morbidity and mortality. Except among patients with known drug allergies, bolus dosing of intravenous unfractionated heparin (UFH) is universally selected as the anticoagulation of choice and is initiated immediately prior to arterial clamping. Precision care is essential to optimise the risk/benefit of its use. However, in practice, heparin use and reversal is a concerningly inexact science. This prospective, observational study has been designed explicitly to provide robust, impartial and industry-free data: (1) to accurately model the the pharmacokinetics (PK) and pharmacodynamics (PD) of UFH boluses and maintenance dosing, and protamine reversal; and, (2) to assess how the anticoagulant effect is monitored with latest iteration viscoelastic haemostatic assay/s (VHA/s), so as to improve the precision of intraoperative care and optimise the risk/benefit balance associated with their use.

Objectives:

Aim 1: Accurately model the PK/PD of IV UFH and protamine in vascular surgery to improve the precision of care and optimise the risk/benefit balance associated with anticoagulant use.

Aim 2: To evaluate the validity of the two-clinically relevant, latest iteration VHA's during heparin use to provide vital information for coagulopathy monitoring and management.

Study methodology:

This is a prospective, observational study of 100 patients undergoing elective vascular surgery requiring intraoperative anticoagulation at tertiary hospitals in Brisbane. Serial blood samples will be concurrently measured for drug level, laboratory coagulation panels, TEG6s and ROTEMSigma parameters to allow accurate pharmacokinetic/pharmacodynamic modelling of intravenous antithrombotics

Outcomes and significance:

1. Addresses an area of need: This detailed ‘real-world’ assessment and analysis of heparin dosing and effects will standardise perioperative heparin use to improve the precision of patient management.

2. Directly influence a sizeable patient population: In 2017, over 2,000 surgeries requiring intravenous heparinisation were performed at TPCH, including 1,000 major vascular/hybrid procedures. As a major surgical hospital, TPCH has an obligation to advance the perioperative care of patients and ensure that best practice are employed to negotiate a safe perioperative period.

3. Be immediately translatable into improved clinical practice. We will ise these data to formulate precise antithrombotic recommendationsand best practice clinical guidelines.

4. Reduce the economic and social burdens of preventable surgical complications: the occurrence of potentially-preventable surgical complications is an important health economics burden for health systems and diminishes community confidence in the service provided.

Funding:

Funding obtained.

Individualised haemodynamic optimisation informed by the lower limit of cerebral autoregulation

Background:

Intraoperative hypotension (IOH) reportedly complicates between 35 - 85% of surgeries. Large observational studies demonstrate that even brief mild IOH below a mean arterial blood pressure (MAP) of 65mmHg are associated with perioperative organ ischaemia and injury (e.g., stroke, acute kidney injury, myocardial infarction). Due to its exquisite sensitivity to hypoperfusion and ischaemia the brain is considered the index organ of acceptable MAP threshold. Cerebral autoregulatory mechanisms maintain stable blood flow in the face of perfusion pressure changes reduction and determine the critical threshold below which vessel dilation cannot compensate for reduced MAP. Pre-clinical data show that this lower limit of cerebral autoregulation (LLA) can be measured using novel mathematical analysis and advanced non-invasive optical measurement of cerebral haemodynamics and metabolism with near infrared spectroscopy (NIRS). Translation and optimization of this to the clinical setting to provide real-time feedback to the anaesthetist and individual optimization of patient blood pressure will be a practice changing development.

Aims:

The aim of this study is to translate and optimize a novel measure of the LLA using NIRS in a non-cardiac surgical population to test its feasibility for individualizing MAP targets to prevent IOH and associated morbidity and mortality.

Study methodology:

This is a prospective observational study of 100 adult patients undergoing non-cardiothoracic elective surgery under general anaesthesia with invasive arterial monitoring at major tertiary hospitals in Brisbane. In addition to the routine standard of care and monitoring, bilateral NIRS optodes (INVOS, Medtronic) will be attached prior to induction and continuously recorded in a time-stamped manner in conjunction with other routinely monitored physiological parameters.

Outcomes and Significance of the project:

This study has the potential to substantially alter how we think about and individualise intraoperative blood pressure management to minimise IOH and associated morbidity and mortality.

The rich dataset obtained will: i) validate and optimise novel analysis techniques for the determination of LLA; ii) provide one of the largest repositories of data on cerebral autoregulatory limits in the general population undergoing surgery; and iii) determine associations with clinical/biochemical correlates of organ ischaemia. These data will form a platform for clinical guideline development and then be used to train and evaluate a convolutional neural network (CNN) for near real-time automated LLA analysis and ultimately inform the development of a prototype point-of-care cerebral autoregulation monitor.

Funding:

Funding obtained.