Case summary

A woman age 75 was an elective admission for right axillobifemoral bypass as treatment for bilateral critical limb ischaemia.

She was reported to have short distance (approximately five metres) claudication and occluded aortoiliac vessels. The patient’s medical history was significant, including ischaemic heart disease with previous left anterior descending artery stenting, oesophageal cancer with liver metastases (in remission), atrial fibrillation (anticoagulated with apixaban), pulmonary hypertension, gastro-oesophageal reflux disease, scleroderma, CREST (calcinosis, Raynaud phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia), type II diabetes mellitus, and a permanent pacemaker for sick sinus syndrome. An echocardiogram eight months earlier demonstrated evidence of decreased ventricular function (ejection fraction 35 per cent—likely overestimated due to moderate mitral regurgitation), and severe pulmonary hypertension (right ventricular systolic pressure [RVSP] estimated at 60 mm Hg, masked further by moderate tricuspid regurgitation).

The patient was reviewed by the anaesthetic team before the operation and classified as ASA 4 (American Society of Anesthesiologists physical status classification system), given her extensive comorbidities. No documentation was provided regarding a preoperative review by the vascular surgeon. The admission notes state that the patient was able to walk 500 metres with a wheelie walker, contradicting the booking form, which states the patient had bilateral critical limb ischaemia. The booking form states that the surgeon had requested that apixaban not be stopped before the operation. This should be noted, given the invasive nature of the procedure along with the fact that the patient was also taking clopidogrel.

The operation was performed with unfractionated heparin (5000 units) provided, in addition to the apixaban and clopidogrel. The consultant surgeon mentioned that after closure of the anastomoses and reversal with protamine, the patient became coagulopathic and unstable with uncontrolled bleeding. Review of the anaesthetic records suggest a sudden change in parameters, with evident loss of output, drop in end-tidal carbon dioxide and elevation in central venous pressure. The patient was given an additional dose of protamine at this time, and massive fluid and blood product resuscitation was administered. A second anaesthetic consultant attended to perform transoesophageal echocardiography (TOE), which demonstrated biventricular failure. Cardiopulmonary resuscitation began with the administration of adrenaline. However, due to significant pulmonary oedema, with fluid within the endotracheal tube inhibiting ventilation, the situation was determined to be futile and the patient died.

Discussion

This was a high-risk patient undergoing limb salvage surgery. Given her poor medical reserve, she was unable to survive the physiological challenges faced throughout the operation.

The combination of a factor Xa inhibitor, antiplatelet agent and heparin throughout the procedure would have made haemostasis challenging. It is unclear why the apixaban was not withheld and bridging achieved with either low molecular weight heparin or unfractionated heparin if there were ongoing concerns regarding the interruption of anticoagulation. This is an area for consideration.

The lack of preoperative clinical notes to demonstrate discussion of risks and indication for the procedure makes it difficult to produce meaningful commentary regarding the choice of operation. Given the patient’s extensive comorbidities, an axillobifemoral bypass would have been reserved for limb salvage. Documentation indicating the patient’s ability to walk 500 metres assisted seems unlikely to be accurate.

Anaesthetic documentation throughout the admission is disappointing, as the records were very limited. It is unclear at what time the protamine was given in relation to the change in the patient’s parameters. No blood gas measurement was performed for more than 90 minutes at the most critical time in the operation when the patient was unstable with evident concerns regarding coagulopathy. An active clotting time measurement was performed following administration of protamine. However, perhaps an earlier rotational thromboelastometry should have been conducted to provide a more accurate assessment of correctable coagulation. A preoperative coagulation screen would also have been beneficial.

Protamine in the setting of known severe pulmonary hypertension, while not an absolute contraindication, would need to have been closely considered and given with extreme care. In the absence of right heart catheterisation and an accurate wedge pressure, it would be assumed that the estimated RVSP was even higher than 60 mm Hg (as this would have been masked by the moderate tricuspid regurgitation). Using protamine in this setting put the patient at high risk of right heart failure.

The time span over which the protamine was administered was not stated within the anaesthetic record. If given rapidly, this could have further contributed to the right heart failure. There were concerns following administration of the protamine, with evident patient deterioration likely further exacerbated by the second dose of protamine. Consideration for elective use of intraoperative TOE throughout this procedure in a high-risk patient would have further mitigated risks with the use of protamine.

Clinical lessons

Perioperative anticoagulation has a significant impact on the morbidity and mortality of surgical patients. An increased number of agents are being used, with some patients on multiple agents. Surgeons need to stay well informed about these drugs, their mechanism of action, adverse reactions to them, and their reversal agents. This requires a deliberate, evidence-based approach to perioperative anticoagulation management, balancing the risks of bleeding with the thromboembolic complications. Various resources are available to help in this endeavour, such as the following:
•    Clinical Excellence Commission, 2018, Guidelines on perioperative management of anticoagulant and antiplatelet agents. Sydney: Clinical Excellence Commission.
•    Queensland Health, Anticoagulant guideline for hospitalised adult patients, February 2022. State of Queensland (Queensland Health) https://www.health.qld.gov.au/__data/assets/pdf_file/0015/1152213/statewide-anticoagulant-guideline.pdf