Heparin-free veno-venous extracorporeal membrane oxygenation in non-trauma patients with difficult airways for surgery

To the Editor: For patients with critical tracheal stenosis in surgery, extracorporeal membrane oxygenation (ECMO) is probably the last, yet safest, choice to ensure definitive airway security. Systemic anticoagulation in the form of heparin is a typical choice. However, heparin is fraught with its own complications that include both bleeding in the patient and clotting within the circuitry.^[1] In recent years, with progressive technological advancements, the application of heparin-free ECMO in trauma patients has been gradually reported but rarely reported in non-trauma patients.^[2] We would like to report three successful cases of heparin-free veno-venous extracorporeal membrane oxygenation (VV-ECMO) in non-trauma patients with difficult airways for surgery, two of which are patients with malignant tumors. This study was approved by the Ethics Committee of the Tongren Hospital (No. TREC2022-KY012). Written informed consent was obtained from the patients. All the three patients with severe tracheal stenosis caused by cervical tumors were admitted for tumor resection or segmental tracheal resection. The narrowest segment of the trachea measured 0.20–0.39 cm in contrast-enhanced CT scan. Awake endotracheal intubation can be extremely risky because of the imminent possibility of total airway obstruction and severe hypoxemia. In addition, tracheostomy was not prepared due to the enlarged tumor and location of the lesion. We established VV-ECMO before anesthesia induction to support adequate ventilation and oxygenation. The parameters for VV-ECMO settings are shown in Table 1. No systemic heparin was given. With oxygenation secured by ECMO, induction of general anesthesia and mechanical ventilation was managed by an endotracheal tube or laryngeal mask. All three patients were provided with lung protective ventilation strategies. It is important to know that not all venous blood is drained from the right atrium, and the residual deoxygenated blood that continues to the pulmonary system will rely on the lungs for gas exchange. Therefore, lung-protective ventilation should be performed if possible for supplemental oxygen and lung protection. The oxygenation for the three patients was maintained by VV-ECMO together with mechanical ventilation intraoperatively.

Table 1 - ECMO settings in the three patients with difficult airway for surgery.

Setting parameters	Case 1	Case 2	Case3
Mode	VV–	VV–	VV–
Drainage cannula location	Right femoral vein	Right femoral vein	Right femoral vein
Drainage cannula size (F)	23	21	21
Return cannula location	Right internal jugular vein	Left internal jugular vein	Right internal jugular vein
Return cannula size (F)	17	17	17
Objective ACT (s)	140–180	140–180	140–180
Duration of ECMO (min)	376	316	344

In case 2, the left internal jugular vein was chosen for blood return because the right internal jugular vein of this patient was severely constricted by the thyroid mass. ACT: Activated coagulation time; ECMO: Extracorporeal membrane oxygenation; VV: Veno-venous.

In our three cases, the activated coagulation time (ACT) measured 140–180 s in surgery, and no complications (especially thrombotic events) related to ECMO were encountered. Thrombotic events are defined as oxygenator failure and/or pump failure, or demonstrated venous thrombosis at the cannulation site or a new diagnosis of pulmonary embolism, deep vein thrombosis, stroke, or other major vessel thrombosis based on diagnostic imaging. We rely upon a fully functional heparinized ECMO circuit (polymethyl-pentene hollow-fiber oxygenator, heparin-coated cannulas, and circuit), to avoid systemic heparin intravenously. A short duration of ECMO may also contribute to this outcome.^[3] Besides, coagulation function test results of all the three cases revealed normal before surgery, and we made adequate fluid intake and strict urine output and ACT monitoring for patients during the operation.

For years, ECMO has played a lifesaving role for many critically ill patients. In 2022 American Society of Anesthesiologists Practice Guidelines, ECMO was also recommended for patients with difficult airways.^[4] However, exposure of blood to the non-biologic artificial surfaces of extracorporeal circuits results in a complex inflammatory response in patients who underwent ECMO, leading to consumption and activation of procoagulant and anticoagulant components. Consequently, anticoagulation has traditionally been used to prevent thrombosis of the ECMO circuit. Based on the expert opinion and consensus, the 2014 Extracorporeal Life Support Organization Anticoagulation Guidelines recommended the use of heparin for systemic anticoagulation with ECMO targeting ACT of 180–220 s. But, it has also increased the risk of excessive bleeding associated with a high mortality. Actually, bleeding has been reported as the major life-threatening adverse event in the first hours after ECMO implantation,^[5] including intracerebral hemorrhage, surgical site bleeding, and gastrointestinal hemorrhage, linking to a higher risk of other complications.

Thanks to the advancement of technology, including centrifugal pumps, oxygenators, and biocompatible circuits, the risk of thromboembolic complications has been theoretically lowered, potentially allowing its application with temporary avoidance of systemic anticoagulants. In recent years, an increasing number of centers have published their experiences with low-dose heparin anticoagulation or heparin-free in patients with a high risk of bleeding, like trauma patients.^[2] Moreover, this strategy has also been reported in lung transplantation. However, in non-trauma patients, especially patients with a relatively high risk of thrombosis, like cancer patients, this application is very rare. The main concern is that insufficient anticoagulation may lead to thrombosis. According to the literature, a fully heparin-coated ECMO circuitry is known to provide sufficient antithrombotic function for limited periods, up to 24–48 h.^[2] A meta-analysis including 7 publications with 553 patients showed no evidence of significant thrombosis complication differences between a low-dose anticoagulation group (targeting ACT 140–160 s) and a standardized-dose anticoagulation group (targeting ACT 180–220 s).^[6]

Based upon these experiences, we successfully proposed three cases of VV-ECMO without systemic heparin anticoagulation in non-trauma patients, two of which were cancer patients. No thrombotic events occurred. Notably, we cannot rule out the possibility of microembolic events, which are invisible to our naked eyes, although Marinoni et al^[7] have detected microembolic signals by transcranial Doppler in patients treated with ECMO, and they have shown encouraging data that microembolic signals did not seem to influence clinical outcomes. More sensitive methods for detection are preferable. There remain many unanswered questions concerning present therapies used in maintaining the hemostatic balance during ECMO, which include the optimal combination, duration, and dosage of antithrombotic agents to limit bleeding and reduce thrombosis.^[8] Our experience suggests that heparin-free VV-ECMO may be safe for non-trauma patients with a short duration use, which can be a great choice for definitely difficult airway in surgery. However, as data on ECMO in non-trauma patients without systemic heparin anticoagulation are limited, larger studies are necessary to validate our observations and elucidate adverse events and benefits associated with this management.

Funding

This study was supported by grants from the Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (No.ZYLX202103); Beijing Hospitals Authority's Ascent Plan (No. DFL20220203).

Conflicts of interest

None.