Peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is often used to support patients with severe cardiopulmonary dysfunction.1 In adults, the femoral artery is commonly used for arterial cannulation because of its accessibility. However, limb ischemia develops in more than 20% of patients with peripheral VA-ECMO and leads a major morbidity or mortality to the patients.2–5 Lower limb perfusion is typically monitored clinically and by Doppler pulse evaluation.6 However, these monitoring methods may be inaccurate and can cause limb hypo-perfusion to go undetected for several hours. Therefore, accurate real-time monitoring method is required for a timely diagnosis of limb ischemia.
The use of near-infrared spectroscopy (NIRS) is well described in the literature, particularly for its applicability in patients undergoing cardiopulmonary bypass (CPB) for the purpose of monitoring cerebral perfusion.7–9 There have been only a few reports of its use in adult patients undergoing peripheral VA-ECMO to monitor lower limb perfusion.6,10,11 To the best of our knowledge, the usage of NIRS to monitor lower limb perfusion in VA-ECMO patients has not been established yet. In this report, we provide our experience of continuous NIRS monitoring for the early detection of lower limb ischemia after femoral cannulation in patients undergoing VA-ECMO.
Between August 2013 and August 2014, we prospectively used NIRS monitoring for the early detection of limb ischemia in adult patients who underwent peripheral VA-ECMO cannulation through the femoral artery. The NIRS monitoring system consisted of INVOS 5100B somatic oximeter (Somanetics, Troy, MI). A pair of sensor pads was placed on the calf of each lower limb. Values that represented the adequacy of tissue oxygenation—regional oxygen saturation (rSO2)—were continuously monitored. Monitoring was initiated within hours upon being placed on ECMO, and was discontinued only after a successful wean to recovery, bridge to transplantation, or death.
ICU Nurses recorded the rSO2 values displayed on the monitor every hour and called physicians if it dropped significantly. By referring to the previously published protocol,10 a significant drop of rSO2 values that requires intervention was defined as a decrease below 40. Although Wong et al.10 defined significant events as drop in rSO2 values below 40 or more than 25% from baseline, we adopted only the first criteria to simplify our protocol. All patients who had significant drops in rSO2 values were assessed first to rule out mechanical causes (improper placement or malfunctioning of sensor pads). Upon close examination, if sensor pads were not the problem, we made an effort to increase oxygen supply to the tissues by increasing ECMO flow, mean arterial pressure, and level of hemoglobin. If rSO2 values were persistently below 40 in spite of these aforementioned managements, we inserted a reperfusion cannula into the superficial femoral artery distal to the arterial ECMO cannula using an ultrasound-guided Seldinger technique at the bedside. We used a double lumen central venous catheter as a reperfusion cannula and connected it with the arterial line of ECMO for distal perfusion. Physical examination was done regularly for the clinical assessment of lower limb perfusion. Pulse evaluation of dorsalis pedis and posterior tibial artery were also performed routinely by Doppler ultrasound (Bidop ES-100V3, Hadeco Inc., Japan).
To compare the outcome, we retrospectively reviewed the medical records of adult patients who had previously received peripheral VA-ECMO without NIRS monitoring between July 2012 and July 2013 (Control group). During this period, perfusion of the lower limb was monitored clinically and by serial Doppler pulse evaluation of dorsalis pedis and posterior tibial arteries. If the clinical signs of limb ischemia—skin color change or calf muscle swelling in the cannulated leg, etc.—were observed or Doppler pulse signals were diminished, we suspected the development of limb ischemia and inserted a reperfusion cannula for distal perfusion by open or Seldinger technique at the bedside. In patients who had worsening tightness in their calf muscle, we directly measured intramuscular pressure and performed fasciotomy if they were diagnosed as compartment syndrome.
This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No: B-1310/221-003).
The statistical analysis for this study was performed with SPSS version 22 (SPSS Inc., Chicago, IL). Continuous variable data were expressed as mean ± standard deviation. Statistical comparisons between NIRS group and control group were made via Student’s t-test for continuous variable and χ2 test for categorical variables. For the analysis of outcome of NIRS group, continuous variables are compared using Mann-Whitney U test and categorical variables are compared by using Fisher’s Exact test. p values of less than 0.05 were considered statistically significant.
Between August 2013 and August 2014, 55 patients were supported with VA-ECMO. We included 28 adult patients who were subjected to NIRS monitoring while being supported with VA-ECMO for more than 24 hours (NIRS group). Adult patients who underwent central ECMO and neonates or children were excluded. Adult patients supported with peripheral VA-ECMO of less than 24 hours were also excluded because most of them died from multiorgan failure or uncontrolled bleeding, rather than ECMO-related complications. Between July 2012 and July 2013, 60 patients underwent VA-ECMO support. Of these, 36 patients who were supported with peripheral VA-ECMO for more than 24 hours were included (Control group). Twenty-four patients were excluded for the same aforementioned reasons. There was no significant difference between age distribution in both groups of patients (p = 0.487). The proportion of female patients was significantly higher in the NIRS group (57.1 vs. 25.0%, p = 0.009). No significant difference was found in the body surface area (BSA, p = 0.432) and arterial cannula-BSA ratio (p = 0.571). We also could not find a significant difference in the frequency of extracorporeal cardiopulmonary resuscitation (ECPR, p = 0.469) and mean duration of ECMO support (p = 0.603) (Table 1).
A significant drop of rSO2 values occurred in 11 patients of the NIRS group (39.3%); and it was recovered in 2 of these patients because of the management to increase oxygen supply to the tissues. However, the other nine patients finally underwent distal perfusion because their rSO2 values did not recover despite management efforts previously mentioned. There was no significant difference in the frequency of distal perfusion between two groups (p = 0.435). The mean time to distal perfusion was shorter in the NIRS group (19.6 ± 21.4 vs. 42.0 ± 69.0 hours), but it was not statistically significant (p = 0.358). There was no significant difference in the rate of loss of Doppler pulse between two groups (p = 0.570). Although no significant difference was found in the frequency of skin color change in the cannulated leg between the two groups (p = 0.164), patients in the NIRS group had a significantly lower rate of calf muscle swelling (7.1% vs. 27.8%, p = 0.036). No patient in the NIRS group underwent fasciotomy because of the development of compartment syndrome, while 13.9% did in the control group, and the difference was statistically significant (p = 0.040) (Table 1). There were no cases requiring amputation in both groups.
Patients in the NIRS group were classified into two groups according to whether or not the clinical signs of limb ischemia were observed after initiation of ECMO (Table 2). No significant difference was found in the age, sex, BSA, arterial cannula-BSA ratio, and mean duration of ECMO support between two groups. The rate of loss of Doppler pulse was significantly higher in the ischemia group (85.7% vs. 28.6%, p = 0.023). In patients in the ischemia group, all patients had significant drops in rSO2 values and underwent distal perfusion. In no-ischemia group, a significant drop of rSO2 values occurred in four patients. In two of these patients, rSO2 values were recovered above 40 after aforementioned management and distal perfusion was not performed. However, the other two patients finally underwent distal perfusion because their rSO2 values did not recover despite same management previously mentioned. Except one patient in the ischemia group, rSO2 values of all patients who underwent distal perfusion were recovered above 40. The mean time to recovery of rSO2 values was 26.3 minutes. The initial rSO2 value was slightly lower in the ischemia group (46.6 ± 18.1 vs. 54.5 ± 12.0) but there was no significant difference between two groups (p = 0.405). Patients in the ischemia group had a larger difference in rSO2 value between two legs at initiation of monitoring (15.0 ± 12.7 vs. 9.7 ± 9.2) but this did not reach statistical significance (p = 0.272). However, patients in the ischemia group had a significantly larger peak difference in rSO2 value between the legs (34.9 ± 13.9 vs. 21.3 ± 9.2, p = 0.023) and the minimum rSO2 value was significantly lower in the ischemia group (22.0 ± 9.4 vs. 43.1 ± 10.0, p < 0.001). In the ischemia group, four patients were successfully weaned from ECMO without limb complications. Of these patients, three finally survived to hospital discharge but one died from pulmonary hemorrhage irrelevant to limb ischemia. Of the three patients who failed to be weaned from ECMO, two patients’ rSO2 values were recovered and they had no limb complications. They died from massive hemoptysis and septic shock during ECMO support, relatively. But the other one died from refractory anaphylactic shock and his rSO2 values were not recovered because of severe hypotension. There was no significant difference in the rate of ECMO weaning (p = 0.144) and survival to hospital discharge between two groups (p = 0.418).
Peripheral VA-ECMO is often used to support patients with cardiogenic shock.1 In adults, the femoral artery is commonly used for arterial cannulation because of its accessibility. Limb ischemia occurs in more than 20% of patients placed on peripheral VA-ECMO via femoral artery.2–5 If limb ischemia progress, acute compartment syndrome can develop, which is a surgical emergency. A delay in its diagnosis is often associated with poor prognosis.4,5 Moreover, many centers may not report limb ischemia when the patient has no chance of survival for other reasons. We also excluded patients who did not survive 24 hours because most of them died from multiorgan failure or uncontrolled bleeding, rather than ECMO-related complications. This means that the incidence of limb ischemia is likely to be much higher than 20%. Therefore, it is important to monitor lower limb perfusion in all VA-ECMO patients undergoing femoral artery cannulation for the early detection of limb ischemia and prevention of compartment syndrome.
Lower limb perfusion is typically monitored by clinical assessment and Doppler pulse evaluation. However, critically ill patients supported with VA-ECMO usually have several conditions that make these monitoring methods ineffective. Typical clinical symptoms of limb ischemia are severe pain and sensory loss. The use of sedative and muscle relaxant in patients undergoing VA-ECMO makes detection of these symptoms to be difficult. Regular assessment to find clinical signs of limb ischemia—loss of palpable pulses, skin color change, calf muscle swelling, etc.—is helpful for monitoring of lower limb perfusion. However, these may be not the early signs but the results of already progressed limb ischemia. Although Doppler pulse evaluation is also widely used method for detection of limb ischemia. It may be also inaccurate in patients with peripheral vasoconstriction or complete absence of a pulse wave in cases fully dependent on nonpulsatile ECMO flow.12 For this reason, not all VA-ECMO patients without Doppler pulse are at risk of limb ischemia. In our study, only 6 of 12 patients (50.0%) who lost Doppler pulse in the NIRS group presented with clinical signs of limb ischemia, and 12 of 18 patients (66.7%) did in the control group. Moreover, these intermittent monitoring methods can cause limb hypo-perfusion to go undetected for several hours. For the lower extremity, many studies revealed irreversible nerve and muscle damage begin after 6 hours of ischemia.13 More recent studies showed that muscle necrosis occurs within the first 3 hours.14 Therefore, accurate real-time monitoring method is required for a timely diagnosis of limb ischemia in patients supported with peripheral VA-ECMO.
NIRS is a noninvasive method that allows continuous real-time monitoring of tissue oxygen saturation. NIRS technology was initially approved for the monitoring of cerebral oxygenation. It is routinely used for cerebral monitoring during cardiovascular surgeries.15 However, now it is also used for the monitoring of tissue perfusion in other organs, especially for the diagnosis of compartment syndrome of the lower extremity.16 Giannotti et al.17 compared NIRS data with direct measurement of compartment pressures in nine adult trauma patients with compartment syndrome. They found that NIRS was associated with higher sensitivity when compared with compartment pressure at the same specificity. Some investigators began to use NIRS monitoring in patients undergoing ECMO. Papademetriou et al.11 described the monitoring of cerebral and tissue oxygenation of four children on ECMO. Wong et al.10 used NIRS in a series of adult ECMO patients for the purpose of monitoring cerebral and lower limb perfusion. They established management protocols for patients undergoing VA-ECMO with clinically significant drops in lower limb rSO2 values. They defined significant events as drop in rSO2 values below 40 or more than 25% from baseline. Their protocol included prophylactic fasciotomy if significant drops in rSO2 values persisted. Among the 17 patients who were placed on VA-ECMO, six experienced a clinically significant drop (35.3%), and four of these six patients required prophylactic fasciotomy against compartment syndrome (66.7%). Although we followed a similar protocol, we adopted only the first criteria to simplify our protocol. As a result, 11 of 28 patients (39.3%) in the NIRS group showed a significant drop in rSO2 values. In two of these patients, rSO2 values were recovered owing to management to increase oxygen supply to the tissue but the other nine patients finally underwent distal perfusion. Figure 1 shows examples of patients whose rSO2 values dropped significantly. The rSO2 values of patient 1 were recovered above 40 after aforementioned management. In case of patient 2, rSO2 values increased above 30 for a while and dropped rapidly below 30. It was recovered above 40 only after insertion of a reperfusion cannula. In all patients who underwent distal perfusion, except only one who died from severe anaphylactic shock, rSO2 values were recovered above 40 and clinical signs of ischemia disappeared. Finally, no patient in the NIRS group developed compartment syndrome requiring fasciotomy. Furthermore, we classified the patients in the NIRS group into two subgroups in accordance with the presence of clinical signs of limb ischemia, and compared rSO2 values in the cannulated leg between two groups. The minimum rSO2 value was significantly lower in the ischemia group as we expected. In addition, we calculated the difference in rSO2 values between the legs to compare the rSO2 values in the cannulated leg with those of the contralateral lower limb. Although no significant difference was found between groups in the initial difference in rSO2 values, the peak difference in rSO2 values while on ECMO was significantly larger in patients in the ischemia group. The protocol established by Wong et al.10 does not include the difference in rSO2 values between the legs. However, we think that it would be additional criteria to make a decision for intervention, although further investigation is needed.
To prevent limb ischemia, prophylactic distal perfusion for every VA-ECMO patient may be another option. A variety of techniques for distal perfusion have been described.18–21 Side-arm graft for bidirectional blood flow can be anastomosed to common femoral artery after surgical exposure. Alternatively, both the common femoral and superficial femoral arteries can be surgically exposed and simultaneously cannulated in opposite directions. Although distal perfusion through the superficial femoral artery after surgical exposure is effective, it can cause significant bleeding and require surgical reconstruction. For this reason, both the common femoral and superficial femoral arteries can be percutaneously cannulated in opposite directions. However, it may be difficult to access the superficial femoral artery percutaneously, especially after initiation of ECMO. We also had one case in which this was attempted but unsuccessful. In one patient in the NIRS group, we tried to percutaneously insert a reperfusion cannula into the superficial femoral artery under ultrasound guidance. But there was no change in rSO2 values despite two attempts of distal perfusion. Finally, we had to remove the reperfusion cannula and inserted a new one after surgical exposure at the bedside. After that, rSO2 values were recovered above 40 in just 10 minutes, and we can rest assured that distal perfusion was successful. The patient finally survived to hospital discharge without limb complications but suffered from groin wound infection. Some institutions use a retrograde posterior tibial artery perfusion instead of antegrade superficial femoral artery perfusion. Spurlock et al.18 surgically exposed the posterior tibial artery and inserted a reperfusion cannula in a retrograde direction. Complication from this technique was minimal, and the procedure was able to be performed at the bedside. Although prophylactic distal perfusion using these techniques is a widely utilized strategy with good success, additional cannulation for prophylactic distal perfusion may be challenging and can cause a number of problems including a significant bleeding or groin wound infection as previously mentioned. The incidence of limb ischemia is about 20% as mentioned earlier. In other words, a significant number of patients on peripheral VA-ECMO may not require any intervention to prevent limb ischemia. In our study, only nine patients (32.1%) in the NIRS group needed a distal perfusion, and 17 patients (61%) in the NIRS group had no ischemia-related events including the drop of rSO2 values even without any prevention. We think that distal perfusion only in patients who exhibit a significant drop in rSO2 values may be enough to prevent compartment syndrome. Although some centers still do not use NIRS to monitor lower limb perfusion, we think it should be considered as a part of standard of care in patients on VA-ECMO. Without NIRS monitoring, it may be difficult to make sure that reperfusion is successful even after prophylactic distal perfusion. We were easily able to confirm that distal perfusion was performed with success if only we observed the recovery of rSO2 values after distal perfusion. Moreover, we had several experiences to detect a thrombotic occlusion of reperfusion cannula during NIRS monitoring because of the sudden drop of rSO2 values and after examination. We could perform a timely revision of occluded reperfusion cannula. However, without real-time monitoring of lower limb perfusion like NIRS, its detection might be delayed for several hours and it could cause lower limb hypo-perfusion.
In addition, the rate of successful ECMO weaning was significantly higher in the NIRS group (78.6% vs. 44.4%, p = 0.006). Patients in the NIRS group also had a significantly higher survival rate to hospital discharge (57.1% vs. 27.8%, p = 0.018). Because our study is nonrandomized, these results may be highly biased by many factors. A randomized study would be necessary to further investigate our findings. However, we think that NIRS is an excellent modality to monitor lower limb perfusion in patients undergoing peripheral VA-ECMO and it may contribute to prevention of compartment syndrome and limb complications.
We think that NIRS monitoring is a useful and reliable method for the early detection of lower limb ischemia in patients undergoing peripheral VA-ECMO. Its application may allow timely correction of perfusion deficits and the prevention of compartment syndrome and limb complications. It would be also possible to improve the quality of care and outcomes of critically ill ECMO patients.
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