The application of ECMO in the 8 reported cases of diffuse alveolar hemorrhage.
Extracorporeal membrane oxygenation (ECMO) has been used more extensively since it became known as a potential bridge therapy, in patients with severe respiratory failure even under optimum conventional mechanical ventilator support, for further definite therapy. In the area of thoracic surgery, ECMO may have already become a useful life-saving tool but studies on this treatment method remain scarce. Currently available reports and case series reveal that patients with massive hemoptysis or critical tracheal stenosis may be benefit from temporary ECMO therapy during the transition of emergent thoracic surgery.
ECMO, also called extracorporeal life support, is a type of cardiopulmonary bypass. In May 1953, Gibbon (Gibbon, 1954) used artificial oxygenation and perfusion support for the first successful open heart surgery. Then it was first also effectively used in an adult patient with acute post-traumatic respiratory failure in 1972 (Hill et al., 1972). The following preliminary studies in 1970s suggested that ECMO could support oxygenation in patients with profound respiratory failure. Recently, the CESAR trial demonstrated that ECMO-based management can improve survival in patients with severe acute respiratory failure (Peek et al., 2009). As technological continues to advance, increasing indications and reports suggest that ECMO has a role to play in the transition of emergent thoracic surgery (Hsu et al., 2011).
There are two types of ECMO: venous-arterial (VA) and venous-venous (VV) ECMO. VV ECMO supports isolated oxygenation failure, whereas VA ECMO provides hemodynamic and respiratory support. Although VA ECMO applies cardiopulmonary bypass, it has more complications due to the alteration of hemodynamic system. As a result, VV ECMO is typically used for respiratory failure while VA ECMO is used for cardiac failure.
2.1. Initiation of ECMO
ECMO is composed of a pump, an oxygenator and a heat exchanger. Once cannulation established, a large volume of blood is extracted from vessels by the mechanical pump. It passes through the oxygenator and heat exchanger. The oxygenated blood is then finally re-infused into the vessels. A complete circuit can be established in 40 minutes by an experience team. In VV ECMO, blood is drawn distally into the right atrium and returned into right atrium in an attempt to minimize recirculation. To achieve this, a drainage cannula is inserted in the right common femoral vein and the other infusion cannula is inserted in the right internal jugular vein. The tip of each cannula should be placed near the junction of the vena cava and the right atrium (fig. 1A). Alternatively, a double lumen cannula can be placed in one major vein (fig. 1B).
In VA ECMO, blood is drawn from the common femoral vein and returned into the femoral artery (fig. 2A). Venous blood is oxygenated and pumped back into arterial circulation. As a result, both the heart and lungs are bypassed. The main concern in femoral artery cannulation is hypoxia of the ipsilateral leg. On the other hand, if native heart function was presence, the oxygenated blood may not reach the proximal aorta and this would result in hypoxia of the heart and upper body. Alternatively, carotid artery cannulation could be performed (fig. 2B). But the risk of watershed cerebral infarction increases when utilizing this method. Because ECMO draw a large volume of blood from vessels, the circuit should be primed with fluid. In most cases, the circuit is re-circulated with normal saline, heparin and crystalloid first. A typical regimen is normal saline 2000ml with heparin 2000units/liter. Once ECMO activated, packed red blood cells are transfused to compensate for the diluting effects of the priming fluid. There is no consensus about the total amount of units that should be transfused. This depends on the volume of the circuit, the perfusion status of patients and the underlying disease. Typically, the goal is to make the hematocrit more than 30% and the mean arterial pressure more than 65mmHg.
2.2. Maintenance of ECMO
During the extracorporeal circulation, thrombosis may occur in the circuit and induce an embolism because of blood surface interaction. As a result, anticoagulation with a continuous infusion of unfractionated heparin is mandatory. The anticoagulant is monitored by activated clotting time (ACT). In general, ACT should be titrated to 210 to 230 seconds. The target should be decreased if the patients have a tendency towards bleeding. Platelets are continuously consumed because of the exposure to the foreign surface and the sheer force. As a result, platelet counts should also be monitored frequently. Sedation is definitely needed during ECMO. Adequate sedation can decrease the anxiety and suffering of patients and put the cardiopulmonary system at rest. The common agents for sedation in ICU are a continuous infusion of midazolam or propofol. Muscle relaxants could be added as well if the patients cannot tolerate use of mechanical ventilators well. Regardless, ECMO should only be utilized when patients are adequately sedated.
ECMO alters hemodynamic stability and induces a large amount of blood run in a device out of body. As a result, complications including localized tissues ischemia and hemostastic instability may occur. The VA ECMO also changes the direction of blood flow which may cause more complications than VV ECMO.
2.3.1. Complications in VV and VA ECMO
Bleeding tendency is usually increased and profound bleeding may even become life- threatening. The occurrence rate of bleeding ranges from 7-34%. The contributing factors are due to the mandatory continuous infusion of unfractionated heparin, platelet consumption and sometimes the underline diseases such as massive hemoptysis and sepsis-related DIC. Effective management depends upon the sites and the causes of bleeding. For example, if the bleeding source is mucosa or gastrointestinal tract, medical management including correcting thrombocytopenia and transfusing with fresh frozen plasma may be necessary. If the bleeding persists or develops into profound bleeding, unfractionated heparin infusion must be withheld temporarily. After the bleeding stops, heparin should be added once again but the target ACT could be adjusted. On the other hand, bleeding from the surgical or device-insertion wounds, including ECMO cannulation site, often requires surgical intervention. This ranges from bedside electrocautery to surgical exploration to achieve bleeding stoppage.
Thrombosis occurs at a rate of 8-17% and heparinization may help to reduce the incidence rate, but could also increase the potential for bleeding events. The balance between homeostasis and thrombosis require frequent clinical and laboratory monitoring. The pressure gradient across the oxygenator is a useful tool to be monitored, and a sudden change in the gradient may suggest a thrombus formation.
Bleeding from a cannulated site is not uncommon. Vascular perforation and arterial dissection may occur during the placement of the cannula. Thus, the utilization of an experienced surgeon is quite important to avoid such complications.
2.3.2. Complications only in VA ECMO
In VA ECMO, oxygenated blood is infused into carotid artery or femoral artery, which forms a countercurrent to native blood flow from the left ventricle. As a result, the increased afterload may worsen the cardiac output of the left ventricle. This results in left ventricle distension, acute pulmonary hypertension and then even pulmonary hemorrhage.
If the infusion cannula is placed in the femoral artery, not only the direction of blood flow of left ventricle, but also the blood flow of aorta is changed. Blood stasis in the aorta is induced if we are not able to maintain left ventricle output. Consequently, aorta thrombosis may develop.
In this type of situation, blood flow from ECMO supplies lower extremities and visceral organs, where as the brain, heart and upper extremities are supplied by the heart itself. It is obvious that the oxygen saturation from the blood vessels supplied by ECMO is much higher than that by heart. Under this type of condition, cerebral and cardiac hypoxia may occur without being recognized if saturation is only monitored by blood sampling from the lower extremities. As a result, monitoring blood saturation during VA ECMO only by digital oxymetry or single arterial line should be avoided.
2.4. Pumpless extracorporeal lung-assisted (pECLA) device
Pumpless extracorporeal lung-assisted device, a novel type of ECMO, had been developed in recent 10 years. In 1967, Rashkind and colleagues first proposed the concept of pECLA (Rashkind et al. 1967). In recent years, the commercialized devices are available and become more and more popular in intensive care unit (Walles, 2007).
During setting up, the blood was drawn from the common femoral artery and sent back to the femoral vein. The pressure gradient driving blood flow in the device was supplied by heart pumping. As a result, pECLA dose not need a centrifugal or roller pump. In this way, it could be set more easily with lower cost and lower dose of heparin than conventional ECMO. However, the device was built to remove carbon dioxide in patient with acute respiratory distress syndrome under lung protective ventilation strategy. Since the blood was drawn from the artery, the oxygenated ability of pECLA was not superior to conventional ECMO. In the management of massive hemoptysis or critical tracheal stenosis, the main problem encountered was hypoxemic respiratory failure, but not hypercapnia. As a result, the application of pECLA in these patients may need more strictly selection.
in summary, ECMO is a powerful therapeutic tool since it can replace the function of the heart and lungs. However, it has several potential complications and their risks increase as the duration of ECMO is prolonged. As a result, it can only serve as a salvage tool in life-threatening conditions and as a bridge to the definite therapy. There are two types of ECMO, the VA type and the VV type. Although VA type can supply perfusion pressure, it obviously has more complications than the VV type. In the field of emergent thoracic surgery, which we will introduce in the following sections, the cardiac function is usually preservative. As a result, VV type ECMO is the first choice in emergent thoracic surgery.
In thoracic surgery, there are 2 conditions, massive hemoptysis and major airway obstruction, where oxygenation is difficult to maintain. Under these conditions, if oxygenation could not be maintained by optimized mechanical ventilation or if the risk of life-threatening hypoxemia is very high, ECMO should be considered.
3. Massive hemoptysis
Massive hemoptysis is an important and potentially fatal event. It has been variably defined as an expectoration of blood amount ranging from 100-1000 ml in 24 hours (Dweik & Stoller, 1999). Since 200 ml of blood could fulfill the anatomical dead space of a major airway and 400 ml of blood might impede the oxygen exchange of alveolar space, massive hemoptysis can be defined as the expectorated blood volume that induces a life-threatening condition by virtue of airway obstruction or severe blood loss (Garzon et al., 1982).
3.1. Conventional management of massive hemoptysis
In the management of massive hemoptysis, protection of the non-bleeding lung and maintenance of adequate oxygen saturation are the major priorities. Then, the second step is to identify the source of the bleeding. The final step is the definite and specific treatment to prevent recurrent bleeding. Among the 3 steps, lung protection and maintenance of oxygenation are the most critical and could determine the outcome of patients. There are five methods for lung protection if the patient has continuous bleeding: decubitus position, selective intubation, double lumen intubation, Fogarty catheter placement and bronchoscope balloon tamponade (Lordan et al., 2003).
At first, an attempt should be made to identify the bleeding side of the lung. After that, the patient should be laid with the bleeding side down to isolate the bleeding lung and ventilate the normal lung. Single lung intubation could be performed if the amount of blood is too great (Gourin & Garzon, 1975). For right side bleeding, the bronchoscope could be placed in the left main bronchus and the endotracheal tube could be inserted in the left lung under the guidance of bronchoscope. For left side bleeding, the endotracheal tube could be placed in the right main bronchus simply by “pushing deeper”; however, this procedure has the risk of occluding the right upper lobe bronchus.
Double lumen endotracheal tube is an alternative method for lung isolation. However, it has four major disadvantages and is not routinely performed in ICU. First, it is difficult for a physician to decide whether double lumen tube should be inserted if the patient only has mild hemoptysis at presentation. Second, it is difficult for an operator to insert a double lumen catheter if the patient was under a hypoxemic status with large amount of blood in the trachea and pharynx. Third, an experienced operator is mandated to avoid the serious result of mal positioning, especially during the transference of patients from ICU to an angiography room. The last disadvantage is that there are still not enough trials to definitively demonstrate whether the double lumen catheter procedure is effective.
Fogarty catheter and bronchoscope balloon tamponade can be applied for lung isolation. A Fogarty catheter (14Fr/100cm length) can be placed over the bleeding bronchus under the guidance of bronchoscope. After inflated, the blood could be restricted in the bleeding side. Bronchoscope balloon tamponade may be more selective in restricting the blood. A 4-7 Fr balloon catheter is passed through the working channel of the bronchoscope and inflated to isolate the lung. However, both interventions need the guidance of bronchoscope. If the patient has massive bleeding, the large amount of blood in the trachea will impede the placement of a balloon catheter.
3.2. ECMO in massive hemoptysis
Several methods for lung isolation have been developed. Their aim is basically the same: to ventilate the good lung and to maintain adequate oxygenation. As a result, if a physician is able to establish a route for oxygenation without depending on inadequate ventilation support, the definite therapy could be applied more safely, even if we fail to protect the good lung. ECMO has such characteristics and might be useful in certain circumstances.
If the patient had “abrupt desaturation”, ECMO can be implemented in 40 minutes by an experienced team. VV ECMO is the first choice, since most patients with massive hemoptysis are threatened by desaturation, rather than hypotension and shock. ECMO can be used as a bridge therapy for the definite treatment, such as angiography embolization and surgery.
Comprehensive review for ECMO use in life-threatening hemoptysis is lacking, and there are still no studies in the related literature on this topic. Since no original study has been published, the experience in application of ECMO in certain patients is largely based on case reports and case series. As early as in 1974, Hanson and colleague reported the first case with pulmonary hemorrhage rescued by ECMO (Hanson et al., 1974). However, not until the 1990s was there was a study or report about the use of ECMO in certain situations. There may be two reasons for this lack of reporting. The first, there is still the argument about the benefit of ECMO in an adult population at that era. And the second, heparinization during
(list in reference)
|Hernandez et al., 2002||Wegener’s granuloma||9||150||Pediatric|
|Kolovos et al., 2002||Autoimmune disease or sepsis||4.9||160-180||Pediatric, Case No. 8|
|Ahmed et al., 2004||ANCA vasculitis||12||Full anticoagulation|
since day 3
|Fujita et al., 2005||Fulminant hepatitis|
s/p liver transplant
|Agarwal et al., 2005||Microscopic polyangitis||7||160-180|
|Arokianathana et al., 2005||Leptospirosis||7||N/A|
|Sun et al., 2006||Idiopathic Pulmonary Hemosiderosis||5||170-200|
|Zhong et al., 2008||Microscopic polyangitis||12||120-200|
ECMO may precipitate further lung hemorrhage. In 2002, Kolovos and colleague reported the largest series and again raised the profile of reconsidering the role of ECMO in severe hemoptysis and pulmonary hemorrhage (Kolovos et al., 2002). They reported 8 children, aged 2 months to 18 years, with pulmonary hemorrhage due to sepsis or autoimmune disease received ECMO as the final therapeutic method because of severe respiratory failure. The eight children exhibited varying degrees of coagulopathy but still received heparinization. The ACT was controlled between 160 to 180 seconds. There was no profound hemorrhage after they received ECMO and all of them were weaned from ECMO successfully after pulmonary hemorrhage was controlled. After that report, although bleeding tendency was still thought to be a relative contraindication for ECMO, it seems that some patients with severe pulmonary hemorrhage could be rescued by ECMO use.
As mentioned above, studies and reports in the related literature in this field are still scarce. To the best of our knowledge, there are only 13 reports about the application of ECMO in massive hemoptysis; 8 of them had diffused alveolar hemorrhage (DAH) (Table 1). In DAH, the use of ECMO has a stronger indication because there is no effective lung protective strategy. The patients in these reports were on ECMO support for 4 to 12 days. Heparin was used at a lower dosage to keep ACT around 120 to 200 seconds, instead of 210 to 230 seconds. Alternatively, delaying the application of heparin seems to be a safe method. All of the patients in these case reports were successfully weaned from ECMO after the underlying causes of severe hemoptysis were under control.
There are 5 reports about the use of ECMO in localized lung hemorrhage (Table 2). In 2 of them, the patients encountered abrupt desaturation during the procedure (bronchial artery embolization and operation), and lung protective therapy was difficult under that condition. Yuan et al. reported a patient with massive hemoptysis due to trauma and a double lumen endotracheal tube was intubated at the ER. However, the patient's clinical condition deteriorated and ECMO was used as a rescue method. In our experience, we have reported a case with bronchiectasis and massive hemoptysis (Hsu et al. 2011). The patient presented with acute respiratory failure due to a rapid progression of severe hemoptysis. A total of 4000 ml of packed red blood cells was transfused within 24 h to keep the hemoglobin level at around 10 mg/dl. The ventilator setting was in the volume control mode, at a positive end-expiratory pressure of 15 cm H2O, and a FiO2 of 100%; however, these setting only could maintain the arterial blood gas at a PaO2 of 62 mmHg. ECMO was applied due to high risk of transferring the patient from the intensive care unit to the angiography room and in-procedure mortality. After bronchial artery embolization successfully, ECMO was weaned 1 day later. No heparinization was performed because of the short term application of ECMO. The patient received left lower lobe lobectomy 2 weeks later due to intermittent small amount of hemoptysis. After the surgery, hemoptysis did not recur. He was discharged in ambulatory condition without any oxygen therapy.
(list in reference)
|Fukui et al., 2006||Pulmonary hypertension||12||40-50 since day 3|
|Bianchini et al., 2007||Swan-Ganz related trauma||2.5||N/A||During operation|
|Bedard et al., 2008||Aorto-pulmonary fistula||N/A||N/A||During bronchial arterial embolization|
|Yuan et al., 2008||Double lumen related trauma||10||60-80|
|Hsu et al., 2011||Bronchiectasis||1||No heparin|
The use of ECMO in massive hemoptysis may be beneficial for certain populations. However, there are still a number of debates about the use of ECMO, since available data is not sufficient in this field. First, setting up ECMO is an invasive procedure, and physicians may not maximize the “conventional therapy” before initiating ECMO. Second, heparinization is usually necessary in ECMO, but it may produce a more severe hemorrhage. Third, ECMO itself may bring about some complications, such as platelet consumption, bleeding and/or thromboembolism.
In summary, maintenance of oxygenation is the most important object in the management of massive hemoptysis. ECMO should be used if all other methods fail or cannot be performed to maintain adequate oxygenation. However, there is still some uncertainty that needs to be addressed, such as the selection criteria of patients and the method of heparinization. Based on currently available evidence, the use of ECMO as a bridge tool for life-threatening hemoptysis can allow a patient to undergo definite therapy more safely.
4. Critical tracheal stenosis
Critical tracheal stenosis can be caused by either malignant or benign lesion. The symptoms may develop abruptly or slowly. In a chronic disease, such as malignancy, chronic inflammatory disease or collagen vascular disease, patients present with progressive dyspnea and stridor. While in acute conditions, such as blunt or penetrating neck trauma, patients may suffer from life-threatening asphyxia. The nature and severity of symptoms depends on the location and the magnitude of the lesion.
4.1. Conventional management of critical tracheal stenosis
Most patients with tracheal stenosis present with chronic symptoms. However, a 50% reduction in the cross-sectional area of the trachea usually results in dyspnea on exertion, whereas a 75% reduction in the cross-sectional area produces dyspnea and stridor at rest. This means that when these symptoms develop, the airway has been severely compromised with impending life-threatening obstruction (Wood, 2002). The patient may be compensated for airway obstruction, but even a small amount of secretion can be lethal. As a result, the strategies of management are different according to the time point of diagnosis.
If the tracheal stenosis is diagnosed early, physicians have enough time to make a complete study. The treatment options include surgical resection, reconstruction, therapeutic bronchoscopy with ablation and airway-stent placement. Before the management takes place, a secure airway could be performed utilizing an efficient method. The fiberoptic bronchoscope (FOB) provides a safe and effective way for airway control (Ovassapian, 2001). With FOB, the lesion could be evaluated vividly and the residual lumen of airway could be estimated. After that, the largest endotracheal tube (ETT) that can pass the lumen should be chosen, since the airway pressure is inversely proportional to the inner diameter of the ETT. To avoid trauma to the airway or the trachea lesion, the ideal size of FOB is 1mm smaller than the internal diameter of ETT. The ideal-sized FOB should be used if available. After determining the size of ETT and FOB, intubation could be performed by experienced anaesthesiologist.
If critical airway stenosis has developed, management will then become more difficult. The position of stenosis is important in this circumstance. For upper airway stenosis, FOB -assisted intubation or emergent tracheotomy can stabilize the airway. For severe mid-level tracheal stenosis, intubation above the stenotic portion can be performed first. After positive pressure ventilation, the residual lumen will be mildly dilated. Then a smaller tracheal tube is placed under the assistance of FOB through trachea or directly placed into main bronchus by the surgeon during surgery.
However, sometimes endotracheal intubation may be impossible, and even dangerous, possibly leading to complete airway obstruction. For most patients, emergent tracheotomy is ineffective because it cannot bypass the obstructive lesion. FOB may precipitate cough, bleeding or further mucosal edema and worsen the obstruction. There are only few choices for patients with this type of life-threatening major airway obstruction. One way is place the patient in a quiet room with very mild sedation and cool humidified oxygen. Nebulized epinephrine and dexamethasone help decrease the contraction and edema of the airway. It may temporary attenuate the symptoms and facilitate subsequent procedure, and FOB -assisted intubation.
4.2. ECMO in critical tracheal stenosis
In patients with critical tracheal stenosis, the key to saving their lives is to maintain safe and efficient gas exchange. However, conventional anesthetic technique has a high risk of causing airway total occlusion, and the risk is inversely proportional to the residual lumen of the airway. As a result, if intubation is performed under a “back up” system, that can maintain adequate oxygenation even under total airway occlusion, it becomes safer for patients and less challenging to anaesthesiologists. Thus, ECMO serves as an ideal tool in this situation.
In paediatric surgery, an increasing number of reports and small-scale patient studies have pointed out that ECMO, either elective or emergent, serves as a good-bridge tool for trachea reconstruction. In neonates with congenital trachea anomalies, ECMO reduces the risk of surgery to allow more precise and unrushed airway reconstruction (Huang et al., 2007)(Kunisaki et al., 2008). Elective ECMO uses in postoperative period also contribute to improve patients’ outcome (Connonlly & McGuirt, 2001).
However, in the field of adults with critical trachea stenosis, we remain in the “case report era.” In 1999, Onozawa and colleagues first reported a case with critical airway obstruction due to thyroid cancer. The diameter of residual lumen of trachea was only 5mm. VA ECMO was applied before induction and the surgery was performed smoothly. After the partial resection of the thyroid tumor and the insertion of tracheostomy, ECMO was decannulated successfully. Following that, there are total 7 case reports with 9 adult patients involving the application of ECMO during critical tracheal stenosis surgery (table 3). These physicians attempted to intubate the patients reported but failed in two of them. One of them even experienced hypoxia cardiac arrest. Emergent ECMO was activated and this saved the patient’s life. Among them, the variable etiologies ranged from benign to malignant origin. The residual lumens of trachea are between 1mm to 5mm. The locations of trachea lesion distribute from 1.5cm above carina to upper level of trachea. VA ECMO was first used and more recently VV ECMO has been applied in cases of critical tracheal stenosis. Both types of ECMO can supply adequate oxygenation for performing the definite therapy.
(list in reference)
|Underlie disease||Diameter & position of residual lumen||Ecmo type||Note|
|Onozawa et al., 1999||thyroid tumor||5mm||VA ECMO|
|Kurokawa et al., 2000||tracheolysis||3mm||VV ECMO|
|Chen et al., 2004||neurofibroma||more than 5.5mm,|
5cm above carina
|N/A||ETT, ECMO stand by only|
|Zhou et al., 2007||Post intubation trachea stenosis||2-3mm,|
1.5cm above carina
|VA ECMO||ETT but failure, emergent ECMO|
6cm below vocal cords
|Jeon et al., 2009||Thyroid tumor||N/A (3x4 cm)||VV ECMO|
|Smith et al., 2009||Papilloma||N/A ( 2.5x2.8 cm), 2.5cm above carina||VV ECMO|
|Papilloma||N/A, extend 2 cm below vocal cords to just above carina||VV ECMO||Bronchoscope ETT related hypoxic cardiac arrest|
|Shao et al., 2009||Bilateral nodular goiter||5mm,||VA ECMO|
In summary, although there is still no original study published in this field, the related case reports have provided useful information. If the residual lumen of trachea is less than 5mm or the ETT cannot pass the lesion, a “stand by” ECMO should be considered before anaesthesia induction. VV ECMO is preferred since it can maintain adequate oxygenation with fewer complications.
And finally, it is worth noting that the criteria for patient selection still needs further investigation to demonstrate the benefits of ECMO as a bridge therapy in critical trachea stenosis. The cost-effectiveness of this method is also worthy of further investigation. Before a definitive conclusion can be made, ECMO should be kept in mind as one option for clinical physicians when handling a patient with critical tracheal stenosis.
During the transition of emergent thoracic surgery, the most important objective is to maintain vital signs, ensuring that they are stable. However, in cases of massive hemoptysis and critical airway stenosis, it remains difficult for physicians to achieve adequate oxygenation since these conditions share the same challenge: difficult airway maintenance. In this field, ECMO serves as the rationale option if conventional therapy cannot achieve adequate oxygenation. Due to the lack of an original study, the role of ECMO in the transition of emergent thoracic surgery still deserves further investigation regarding its utilization and cost-effectiveness. Based on the current evidence available, ECMO could make the transition of emergent thoracic surgery safer.