USE OF VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION WITHOUT HEPARIN FOR A PATIENT WITH CONCOMITANT INJURY Skopets A.A., Zharov A.S., Potapov S.I., Afonin E.S., Utegulov M.G., Kozlov D.V., Chibirov S.K., Mukhanov M.L., Shevchenko A.V., Baryshev A.G., Porkhanov V.A.

Research Institute-Ochapovsky Regional Clinical Hospital No.1,

Kuban State Medical University, Krasnodar, Russia

Due to technical progress and accumulated clinical experience, the use of venovenous extracorporeal membrane oxygenation (vv-ECMO) has become the therapeutic standard for salvation of lives of patients with acute respiratory distress syndrome (ARDS) [1-3]. The expert group made a conclusion after a randomized controlled study (CESAR) of ECMO: it is necessary for severe ARDS [4]. Realization of ECMO requires for a well-trained multi-disciplinary team. Its realization can lead to serious complications relating to disordered blood flow in extremities, blood loss etc. Sometimes, ECMO plays a role of a life-saving procedure, when other methods are non-efficient [5, 6].

Anticoagulation and hemotransfusion are standard for ECMO to prevent platelet activation and subsequent catastrophic insufficiency of extracorporeal contour of thromboembolic complications.

Development of centrifuge pumps of new generation, and low-resistant polymethylpentene oxygenerators was directed to a decrease in thrombogenicity of ECMO-contour and intracontour hemolysis [2, 7]. Anticoagulation by itself does not cause any hemorrhagic complications, which are common (15-25 %) and can be fatal [1, 3, 10]. Less severe complications in critically ill patients are determined by anemia and risks relating to high transfusion requirements. High risk of complications in ECMO in patients with severe concomitant injury stimulates the interest to minimization of anticoagulation strategy.

Severe concomitant injury is a cause of death in young people in 55-80 % of cases; a cause of lethal outcome is often related to lung involvement since injuries to chest organs are identified in 50 % of patients [11, 12]. Hemorrhagic shock and post-injury severe respiratory insufficiency are common pacemaker of fatal complications [13].

Despite the fact that the first successful use of ECMO was realized in treatment of posttraumatic ARDS in 1971, this technique for treatment of patients with severe concomitant injury did not become main due to hemorrhagic complications [14].

The literature describes some cases of ECMO use for patients with various injuries, with some patterns and sometimes poor outcomes [11, 14-19]. The received results and high risk of bleeding progression do not stimulate the wide use of ECMO in this population of patients [9]. More detailed studies of data bases showed that patients with injuries and extracorporeal support demonstrated the survival rate of 44-74.1 % [10-15], like the previously reported survival of 58 % in general population of adults with respiratory ECMO [16]. Extracorporeal membrane oxygenation maintains systemic oxygenation of tissues when pulmonary function is disordered. However it is considered that ECMO is contraindicated for some patients, especially for ones with risk of bleeding after use of systemic anticoagulants, for example, in patients with closed chest injuries with bleeding relating to lung contusion and other organ injuries [8].

Therefore, it is important to pay attention to the factors, which promote bleeding or coagulopathy. The use of ECMO without heparin can be a key to salvation of the problem of systemic oxygenation during treatment. Several cases of ECMO in patients with massive hemothorax after pulmonary parenchymal injury were described [10]. In this report, we present a clinical case of successful use of ECMO without heparin for a female patient (age of 19) with respiratory failure determined by extensive bilateral lung injury.

Objective – to discuss the possibilities of extracorporeal life support in patients with trauma profile.

The study was conducted in compliance with World Medical Association Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, 2013, and the Rules for Clinical Practice in the Russian Federation (the Order by Healthcare Ministry of Russia, June 19, 2003, No.266), with the written consent for participation in the study and for use of personal data.

MATERIALS AND METHODS

The patient, age of 19, was admitted on September 26, 2019, on the fourth day after a road traffic accident. The diagnosis was: "Concomitant injury to the head, the chest, the spine, the pelvis and extremities; contused wounds of the face; a closed chest injury; lung contusion; pneumomediastinum; closed fractures of ribs 1-5 to the right and rib 2 to the left; a closed fracture of middle one-third of both bones of the right leg with displaced fragments; a lineal fracture of anterior arch of C1 without displaced fragments; a fracture of transverse processes of Th1, Th3-7 without displacement of fragments to the right".

In the level 2 trauma center (central regional hospital), the fracture of leg bones was fixed with external fixation apparatus. Due to progression of respiratory failure, a decision was made to transfer the patient to the level 1 trauma center (regional clinical hospital). The patient was transported by an ambulance car. Her condition was very severe, and was conditioned by the concomitant injury, severe respiratory failure, unstable hemodynamics and metabolic disorders. Skin surface was edematous, pale cyanotic. There were some scratches on her right cheek, nose, right and left ankles, and on the dorsal surface of the left foot.

The patient was in condition of drug sedation (consciousness was clear without sedation; psychomotor agitation was +2 according to RASS). Artificial lung ventilation was conducted with Drager Evita-4 with SIMV mode; ventilation parameters: Vt – 550 ml, f – 14/min, FiO₂ – 80-100 %, Рреак 35 cm H₂O, PEEP 14 cm H₂O. Vesicular breathing was weak. There were some moist rales. SpO₂–45-60 %. Hemodynamics was unstable. Infusion of noradrenaline − 0.1-0.3 µg/kg/min, AP − 100-115/55-79 mm Hg, HR − 95-110 min, sinus rhythm.

Note: SIMV − synchronized intermittent mandatory ventilation, Vt − tidal volume (ml), f – respiratory rate, FiO₂−oxygenation index, Рреак – peak flow value, PEEP −positive end-expiratory pressure, SpO₂ – blood oxygen saturation.

Fibrobronchoscopy showed bilateral diffuse catarrhal endobronchitis with mucous hemorrhagic secretion.

A study of arterial blood gases: pH – 7.31, PaCO₂ – 42.4 mm Hg, PaО₂ – 50.6 mm Hg, Hb – 77 g/l, SаO₂ – 76.6 %, BE – 1.6 mmol/l, HCO₃– 21.2 mmol/l, К⁺ – 3.51 mmol/l, Na⁺ – 138.4 mmol/l, glucose – 5.8 mmol/l, lactate – 4.61 mmol/l.

Leg fractures were fixed with external apparatus.

The patient had severe respiratory insufficiency, ARDS infiltration in four quadrants, РаО₂/FiO₂ – 128, Рреак – 35 cm H₂O, PEEP – 17 cm H₂O, compliance − 39 ml/cm H₂O, Murrey index − 3.5. A decision on initiation of vv-ECMO was made owing to progressing respiratory failure, despite of high risk of hemorrhagic complications at the background of systemic heparinization.

On September 27, 2019, at 11:35 a.m., cannulation of the right femoral artery and the right internal jugular vein was performed under X-ray control in the catheterization laboratory. Cannulas 17Fr and 19Fr were installed. Venovenous extracorporeal membrane oxygenation was initiated (the scheme − right femoral vein − right internal jugular vein) with perfusion rate of 5-6.5 l/min/m², V – 4 l/min, DO₂– 100 %. Systemic anticoagulation was conducted only before cannulation with single-stage intravenous introduction of 2,500 units of heparin. The same dose of heparin was added to primary volume of ECMO-contour. Activated clotting time before cannulation was 158 sec.

ALV was continued with BiPAP with parameters: FiO₂– 50 %, f – 16/min, Pinsp – 17 cm H₂O, PEEP – 5 cm H₂O.

Note: BiPAP – ventilation mode at two levels of CPAP with switching between pressure levels through targeted time intervals, Vt − tidal volume (ml), f – respiratory rate, FiO₂−oxygenation index, Pinsp – high pressure phase, PEEP − positive end-expiratory pressure, DO₂– percentage of oxygen delivered to mixer of ECMO device.

Arterial blood gases: pH – 7.37; PaCO₂ – 41.8 mm Hg; PaО₂ – 59 mm Hg, Hb – 95 g/l; SO₂ – 83.4 %; К+ – 3.5 mmol/l; Na+ – 136 mmol/l; glucose – 6.8 mmol/l; lactate – 3.65 mmol/l; BE – 1.6 mmol/l; HCO₃– 23.0 mmol/l.

Echocardiography showed ejection fraction (EF) > 55 %, tricuspid regurgitation 2-3+, pulmonary hypertension (systolic pressure in pulmonary artery − 50-60 mm Hg).

Computer imaging (CI) of chest organs identified some negative time trends of bilateral infiltrative process in the lungs, and pneumomediastinum. There were fractures of ribs 1-5 to the right, and rib 2 to the left, fractures of transverse processes Th1 and Th3-7 to the right.

Extracorporeal respiratory support with vv-ECMO was conducted within 6 days. Within the whole period of vv-ECMO, volumetric rate of perfusion was within 4.5-5 l/min, with rotation rate of the centrifuge pump of 4,000-5,000 r.p.m. Oxygenation was controlled with monitoring of gas composition of arterial and venous blood, pulse oximetry, and oximetry with near-infared strectroscopy (NIRS) on the right forearm, right and left legs. It allowed estimating the oxygenation of the whole body, and peripheral perfusion of the extremity with the cannula. Left leg NIRS was rSO2 – 68-65 %, for the right leg − 38-41 %, for the right forearm − rSO2 – 70-67 %. The cause of decreasing oxygenation in the right leg was edema after a fracture of the middle one-third of both bones of the right leg with displacement of fragments.

The time course of changes in gas composition of arterial blood is presented in the table 1.

Table 1

Time course of arterial and venous blood gases during VV-ECMO

Value	At admission	Before ECMO	day 1 of ECMO	day 2 of ECMO	day 3 of ECMO	day 4 of ECMO	day 5 of ECMO	day 6 of ECMO	Before weaning from ECMO	day 1 after ECMO	day 2 after ECMO
Value	26.09.19	27.09.19	27.10.19	28.10.19	29.10.19	30.10.19	01.11.19	02.11.19	03.11.19	04.11.19	05.11.19
*Artery*
*FiO₂*	0.8	1.0	0.5	0.5	0.35	0.5	0.5	0.5	0.5	0.3	0.3
pH	7.31	7.41	7.37	7.52	7.47	7.42	7.42	7.47	7.43	7.51	7.46
PaCO₂	42.40	38.50	41.80	32.90	34.80	37.10	40.00	33.90	36.50	33.00	34.10
PaO₂	50.60	128.90	58.80	81.30	84.00	73.60	97.80	81.60	98.50	165.00	92.10
Hb	77.00	91.00	95.00	103.00	156.00	174.00	155.00	136.00	100.00	177.00	163.00
SO₂	76.60	98.60	83.20	95.40	95.90	91.50	97.10	96.30	97.30	99.20	96.70
K+	3.51	3.98	3.48	2.61	3.58	4.00	4.17	3.90	4.10	3.49	3.55
Na+	138.40	140.00	135.70	137.00	137.10	135.00	135.50	137.00	138.00	133.60	132.30
Glucose	5.80	4.30	6.80	5.60	5.50	5.00	5.40	5.50	6.90	6.50	5.20
Lactate	4.61	2.06	3.65	2.81	2.10	1.80	1.71	1.60	1.30	1.90	1.30
BE	-4.90	-0.40	-1.60	4.00	1.80	-0.10	1.40	1.20	0.50	3.10	0.10
HCO_3-	20.40	24.10	23.00	28.10	26.40	24.50	25.70	25.96	25.10	27.90	25.20
*Vein*
pH	6.99	-	7.41	7.53	7.46	7.39	7.36	-	-	-	-
PvCO₂	53.00	-	36.60	31.70	38.50	44.40	52.70	-	-	-	-
PvO₂	30.10	-	43.80	67.60	42.80	46.30	36.00	-	-	-	-
SvO₂	20.90	-	66.20	92.20	67.00	68.80	46.20	-	-	-	-
Лактат Lactate	9.10	-	3.27	2.70	1.94	1.93	1.66	-	-	-	-
BЕ	-16.80	-	-1.60	3.60	3.60	1.30	4.30	-	-	-	-
HCO_3-	10.40	-	22.90	27.80	27.00	24.60	26.60	-	-	-	-

Note: pH – acid-alkali balance of blood, PaCO₂– arterial blood carbon dioxide partial pressure, Hb – hemoglobin level, SO₂ – oxygen saturation of arterial blood, BE – deficiency or excess of bases for whole extracellular fluid, including blood, PvCO₂ – carbon dioxide partial pressure of venous blood, PvO₂– oxygen partial pressure of venous blood.

Systemic heparinization was not conducted. However, clexane (40 mg, subcutaneously, 2 times per day) was prescribed. Owing to slight bleeding around the outflow cannula, clexane was cancelled on the next day, and prescribed again after weaning from ECMO.

Monitoring of hemoglobin, hematocrit, platelets, blood clotting, antithrombin III, D-dimers, activated clotting time and free hemoglobin was performed each day. These values are presented in the figure 1-4.

Figure 1

Time course of changes in values of coagulogram during VV-ECMO. Note: PTT (sec.) – prothrombin time, INR – international normalised ratio, APTT (sec.) – activated partial thromboplastin time, AT III (%) – antithrombin III activity.

Figure 2

Time course of changes in hemoglobin, hematocrit and platelets during VV-ECMO

Figure 2 Time course of changes in hemoglobin, hematocrit and platelets during VV-ECMO

Figure 3

Time course of changes in D-dimer during VV-ECMO

Figure 3 Time course of changes in D-dimer during VV-ECMO

Figure 4

Time course of changes in activated coagulation time during VV-ECMO

Figure 4 Time course of changes in activated coagulation time during VV-ECMO

Analgesia and sedation were performed by means of continuous infusion of phentanyl (1.5-0.5 µg/kg/h). Due to need for daily bronchoscopy and activation of the patient, on the third day of vv-ECMO, she received transcutaneous dilatation tracheostomy. Owing to gastric stasis and ischemic hypoxic enterocolitis, the patient received parenteral nutrition. On the 4th day of ECMO, the intestinal probe was installed through endoscopic approach, and enteral nutrition was initiated.

The trigger level of hemoglobin in vv-ECMO was determined by us as 12 g/l. During extracorporeal membrane respiratory support without heparin infusion, the patient received 12 doses of packed red blood cells, and 26 doses of fresh-frozen plasma (FFP).

The table 2 presents the data on transfusion of blood components.

Table 2

Transfusion of blood components during VV-ECMO

Blood components	26.09.19	27.09.19	27.09.19	28.09.19	29.09.19	30.09.19	1.10.19	2.10.19	3.10.19
Erythrocytic suspension, ml	373	353	323	-	323	-	-	333	303
	353	-	353	-	303	-	-	-	353
	-	-	333	-	-	-	-	-	-
Total (erythrocytic suspension)	726	353	1009	0	626	0	0	333	656
Fresh frozen plasma (FFP), ml	280	300	600	210	-	600	-	600	-
	290	280	600	600	-	600	-	600	-
	-	-	600	600	-	-	-	-	-
	-	-	280	300	-	-	-	-	-
	-	-	-	220	-	-	-	-	-
Total (FFP)	570	580	2080	1930	0	1200	0	1200	-

The changes in time course of inflammatory-infiltrative process in the lungs was controlled with recurrent computer imaging of the chest organs. The first examination after transfer from the central regional hospital showed some regions of low airiness by type of "ground glass" which interfused and were more apparent in the lower parts. On the second day after initiation of ECMO, the increase in intensity and incidence of changes in lung parenchyma was found (Fig. 5-7).

Figure 5

Patient, age of 19. Thoracic CT before VV-ECMO

Figure 5 Patient, age of 19. Thoracic CT before VV-ECMO

Figure 6

Patient, age of 19. Thoracic CT before VV-ECMO

Figure 6 Patient, age of 19. Thoracic CT before VV-ECMO

Figure 7

Patient, age of 19. Thoracic CT before VV-ECMO

Figure 7 Patient, age of 19. Thoracic CT before VV-ECMO

On the 5th day of ECMO, chest CI showed some positive trends in bilateral infiltrative process in the lungs (possibly, ARDS) (Fig. 8-10).

Figure 8

Patient, age of 19. Thoracic CT during VV-ECMO

Figure 8 Patient, age of 19. Thoracic CT during VV-ECMO

Figure 9

Patient, age of 19. Thoracic CT during VV-ECMO

Figure 9 Patient, age of 19. Thoracic CT during VV-ECMO

Figure 10

Patient, age of 19. Thoracic CT during VV-ECMO

Скопец_Рисунок 10.jpg

At the moment of admission, the bronchoscopic study showed pale pink mucosa with hemorrhage; the vascular pattern was blurred. There was a moderate amount of mucous hemorrhagic secretion in the lumen of bronchi of the lower lobes. During videobronchoscopy, which was performed for transcutaneous puncture tracheostomy four days later, the right and left-sided bronchial mucosa was moderately edematous, with hyperemia. The vascular pattern was not visible. There was a moderate amount of cloudy mucous purulent secretion.

RESULTS

On the sixth day after a successful test with cancellation of oxygen-air mixture to ECMO-contour, the patient was weaned from ECMO.

The components of ECMO-contour were properly studied. There were not any clots and thrombotic deposits on the walls of the oxygenator, on the centrifuge pump and on the trunks (Fig. 11-13).

Figure 11

Contour after VV-ECMO without heparin

Figure 10 Patient, age of 19. Thoracic CT during VV-ECMO

Figure 12

Centrifugal pump after VV-ECMO without heparin

Figure 12 Centrifugal pump after VV-ECMO without heparin

Figure 13

Oxygenator after VV-ECMO without heparin

Figure 13 Oxygenator after VV-ECMO without heparin

On the next day after weaning from ECMO, the tracheostomy tube was removed, and high-flow oxygen therapy with FiO₂ of 30 % was initiated. On the fourth day after weaning from ECMO, osteosynthesis was carried out. On the seventh day after surgery, the patient's condition was satisfactory, and she was transferred to the hospital according to her place of residence.

DISCUSSION

We described the case of severe closed injury, which required for ECMO without heparin due to massive hemorrhage after a road traffic accident. We can find a lot of reports on ECMO without heparin in severe closed injury to the chest, but all of them present retrospective, observational or cohort studies [11, 14-19], and presentations of case histories are rare [9, 10]. Therefore, we described the detailed report on a severe blunt chest injury with CT images of the chest, bronchoscopy and laboratory data.

Annually, approximately 5 million of deaths are caused by severe trauma [13, 27]. A lot of patients well response to special techniques of trauma management, including infusion therapy, ALV and other invasive procedures. However patients with simultaneous severe chest trauma and hemorrhagic shock show quite poor prognosis. The main aims of management of patients with severe closed chest trauma and hemorrhagic shock are recovery of blood clotting by means of transfusion of blood components (erythrocytes, platelets, fresh frozen plasma), surgical arrest of bleeding, and maintenance of body temperature [15, 16]. It is considered that in absence of bleeding from organs except for lungs, the use of ECMO will possibly cause the low risk of additional hemorrhagic problems [34]. However in presence of bleedings from other injuries, ECMO should be considered with caution, depending on possibility of control of any additional source of hemorrhage. Early initiation of ECMO has a possible risk of ECMO-associated complications in trauma patients, especially with hemorrhage. Trauma-induced coagulopathy is a well-described process relating to significant values of morbidity and mortality [28-31]. Bleedings cause serious problems for treatment of trauma patients. Hemorrhagic complications are registered in 35-59 % of patients with ECMO [17, 19]. In attempts of minimizing risk of bleeding in patients with ECMO in the posttraumatic period, some special strategies of management were described, such as ECMO without heparin, and titration of activated clotting time (ACT) [13, 17, 18].

Within the last decades, some technical advances in ECMO such as heparin-coated contours, and polymethylpentene oxygenerators decreased the thrombogenic potential, and, as result, softened the demands for anticoagulopathy [32]. These technical advances allowed individualization of estimation of bleeding and subsequent changes in anticoagulation parameters in trauma patients, with use of minimally possible anticoagulopathy when required [13, 18]. ECMO without heparin is also considered for such patients. In similar manner, if active bleeding from bronchi is identified (also bleeding after lung contusion), the possibility of control of these hemorrhage sources should be considered in initiation of ECMO regardless of bleedings from other organs. It is considered that ECMO without heparin is appropriate for trauma patients, despite of worse survival [20]. Therefore, for prevention of thrombosis and clotting, we focused on blood flow intensity in ECMO. In our case, for prevention of thrombosis, considering the possibility of clot formation in use of ECMO without heparin, for "the rest" of lungs, we installed the flow at higher rate than usual blood flow in ECMO. In this period, it is very important to check the values of blood clotting, ACT, APTT, prothrombin and D-dimers. D-dimer is the very sensitive marker of blood clotting. In our case, as we expected, the level of D-dimer was gradually decreasing as compared to the basic level (determined by posttraumatic hematoma). Therefore, there were not any complications relating to clot formation during vv-ECMO. Immediately before weaning from vv-ECMO, the level of D-dimer increased above the basic level.

Therefore, considering the use of ECMO for improvement in oxygenation in patients with severe injury, and bleeding, which is difficult to control, it is recommended: 1) single bolus of small dose of heparin (2,500 units) before vascular cannulation, and the same dose for primary volume of pump contour; 2) higher rates of blood flow as compared to recommended rates for non-trauma patients, to prevent thrombosis in ECMO-contour. It is the new and important information on treatment of severe concomitant injury.

Damage control focuses on rapid arrest of bleeding and on stabilization of main vital functions − breathing and blood circulation. Arlt et al. reported that use of heparinless ECMO is appropriate for survival of patients with closed injury, respiratory failure and hemorrhagic shock [13]. Despite of contraindications, for patients with closed trauma and hemorrhagic shock, surgical correction with subsequent ECMO can be realized if bleeding is well controlled. In this case, we used ECMO since the patients had no irreversible injuries, and bleeding control was adequate after fixation of the main fractures. The results of computer imaging did not identify any ALV-related barotrauma or hemorrhage-related complications.

From other side, long term heparinless ECMO was successfully used for patients with severe traumatic brain injury (TBI) [21, 33]. It is possible that higher frequency of TBI will show independent correlation with worse results in patients with ECMO and traumatic respiratory insufficiency.

We think that further use of heparin makes the clinically significant influence, and further studies are required for identification of this influence, especially in patients with TBI.

Therefore, ECMO has some degree of risk for patients with serious trauma. So, ECMO can be the first line of therapy in patients with traumatic lung contusion, ARDS and alveolar bleeding, and its use is disputable for patients with injuries and bleeding.

However for patients with severe traumatic lung injury and alveolar bleeding with hard-to-treat hypoxemia and hypercapnia, the use of ECMO can be a key to survival in such situation.

CONCLUSION

ECMO can be an additional technique for treatment of adult patients with severe closed lung injury or acute respiratory failure resistant to standard ventilation. With appropriate observation, ECMO can be the safe and efficient technique for life salvation in patients with severe chest trauma and concurrent hemorrhagic shock.

Information on financing and conflict of interest

The study was conducted without sponsorship.

The authors declare the absence of any clear and potential conflicts of interests relating to publication of this article.