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Objectives: Despite increasing use and promising outcomes, venovenous extracorporeal membrane oxygenation (V-V ECMO) introduces the risk of a number of complications across the spectrum of ECMO care. This narrative review describes the variety of short- and long-term complications that can occur during treatment with ECMO and how patient selection and management decisions may influence the risk of these complications.Data Sources: English language articles were identified in PubMed using phrases related to V-V ECMO, acute respiratory distress syndrome, severe respiratory failure, and complications.Study Selection: Original research, review articles, commentaries, and published guidelines from the Extracorporeal Life support Organization were considered.Data Extraction: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review.Data Synthesis: Selecting patients for V-V ECMO exposes the patient to a number of complications. Adequate knowledge of these risks is needed to weigh them against the anticipated benefit of treatment. Timing of ECMO initiation and transfer to centers capable of providing ECMO affect patient outcomes. Choosing a configuration that insufficiently addresses the patient's physiologic deficit leads to consequences of inadequate physiologic support. Suboptimal mechanical ventilator management during ECMO may lead to worsening lung injury, delayed lung recovery, or ventilator-associated pneumonia. Premature decannulation from ECMO as lungs recover can lead to clinical worsening, and delayed decannulation can prolong exposure to complications unnecessarily. Short-term complications include bleeding, thrombosis, and hemolysis, renal and neurologic injury, concomitant infections, and technical and mechanical problems. Long-term complications reflect the physical, functional, and neurologic sequelae of critical illness. ECMO can introduce ethical and emotional challenges, particularly when bridging strategies fail.Conclusions: V-V ECMO is associated with a number of complications. ECMO selection, timing of initiation, and management decisions impact the presence and severity of these potential harms. [ABSTRACT FROM AUTHOR]

Objectives: Extracorporeal membrane oxygenation has become integral to critical care. Data informing optimal extracorporeal membrane oxygenation education modalities are lacking. We aimed to compare the effect of high-fidelity simulation versus interactive mobile learning on extracorporeal membrane oxygenation knowledge acquisition and retention among clinicians.Design: Observer-blinded, randomized controlled trial.Setting: A single academic medical center.Subjects: Forty-four critical care clinicians with limited extracorporeal membrane oxygenation experience.Interventions: Participants were randomized to receive: 1) simulation: three high-fidelity training scenarios, 2) QuizTime: 15 total multiple-choice questions delivered over 3 weeks via mobile device, or 3) experiential: no formal training. Participants completed a survey, written knowledge examination, and simulation assessment prior to randomization, immediately following the intervention, and 4 month postintervention.Measurements and Main Results: The primary outcome was knowledge about extracorporeal membrane oxygenation assessed by score on the immediate postintervention written examination. Secondary outcomes included performance in extracorporeal membrane oxygenation simulation postintervention and 4 months later assessed by a rater blinded to group assignment. Clinicians randomized to simulation (n = 15), QuizTime (n = 14), and experiential (n = 15) had similar baseline characteristics. Adjusting for baseline knowledge, postintervention examination scores were higher in the simulation group (90.0%; interquartile range, 85.0-90.0%) than the QuizTime group (70.0%; interquartile range, 65.0-80.0%; p = 0.0003) and the experiential group (75.0%; interquartile range, 65.0-80.0%; p = 0.001). Scores did not differ between the groups at 4 months (p > 0.05 in all analyses). In postintervention extracorporeal membrane oxygenation simulations, the simulation group demonstrated shorter time to critical action compared with QuizTime (80.0 s [interquartile range, 54.0-111.0 s] vs 300.0 s [interquartile range 85.0-300.0 s]; p = 0.02) and compared with both QuizTime (45.0 s [interquartile range, 34.0-92.5 s] vs 255.5 s [interquartile range, 102.0-300.0 s]; p = 0.008) and experiential (300.0 s [interquartile range, 58.0-300.0 s]; p = 0.009) at 4 months.Conclusions: Simulation was superior to QuizTime and experiential learning with regard to extracorporeal membrane oxygenation knowledge acquisition. Further studies are needed to ascertain the effect of these interventions on knowledge retention, clinical performance, and patient outcomes. [ABSTRACT FROM AUTHOR]

Eccentric overload is used to enhance performance. The purpose of this study was to investigate the acute effects of eccentric overload on concentric front squat performance. Twenty resistance-trained men (age = 23.80 ± 1.82 years, height = 1 76.95 ± 5.21 cm, mass = 83.49 ± 10.43 kg, 1 repetition maximum [1RM] front squat = 131.02 ± 21.32 kg) volunteered. A dynamic warm-up and warm-up sets of front squat were performed. Eccentric hooks were added to the barbell. They descended for 3 seconds, until eccentric hooks released, and performed the concentric phase as fast as possible. There were 3 randomly ordered conditions with the concentric phase always at 90% 1RM and the eccentric phase at 105, 110, and 120% of 1RM. Two repetitions were performed for each condition. A repeated measures analysis of variance was used to determine differences. For peak velocity, there were main effects for time and condition (p < 0.05), where post (1.01 ± 0.10 m⋅s-1) was greater than pre (0.96 ± 0.11 m⋅⋅s-1) and 120% (1.03 ± 1.11 m⋅s-1) was greater than 105% (0.99 ± 0.13 m⋅s-1). For peak power, there was a main effect for condition where 120% (2,225.00 ± 432.37 W) was greater than 105% (2,021.84 ± 563.53 W). For peak ground reaction force, there were main effects for time and condition, where post was greater than pre and 120% was greater than 105%. For the rate of force development, there was no interaction or main effects. Eccentric overload enhanced concentric velocity and power; therefore, it can be used by strength coaches and athletes during the power phase of a training program. It can also be used to prescribe supramaximal loads and could be a tool to supplement the clean exercise because the front squat is a precursor. [ABSTRACT FROM AUTHOR]

Stretching is used to increase joint range of motion, but the acute effects can decrease muscle strength. However, this may depend on the population or mode of stretching. The purpose of this study was to compare the acute effects of static vs. ballistic stretching on strength and muscular fatigue between ballet dancers and resistance-trained women. Fifteen resistance-trained women (age 23.8 ± 1.80 years, mass 67.47 ± 7.77 kg, height 168.30 ± 5.53 cm) and 12 ballet dancers (age 22.8 ± 3.04 years, mass 58.67 ± 5.65 kg, height 168.00 ± 7.69 cm) performed 5 days of testing. The first day was control (no stretching), whereas the other 4 days were static or ballistic stretching in a counterbalanced order. Range of motion, strength, and fatigue tests were also performed. Both groups demonstrated a significant decrease in hamstrings strength after static (102.71 ± 2.67 N$m) and ballistic stretching (99.49 ± 2.61 N$m) compared with control (113.059 ± 3.25 N$m), with no changes in quadriceps strength. For fatigue, only ballet dancers demonstrated a decrease from control (71.79 ± 4.88%) to ballistic (65.65 ± 8.19%), but no difference with static (65.01 ± 12.29%). These findings suggest that stretching decreases hamstrings strength similarly in ballet dancers and resistance-trained women, with no differences between modes of stretching. However, ballistic stretching only decreased muscular fatigue in ballet dancers, but not in resistance-trained women. Therefore, no stretching should be performed before strength performance. However, ballistic stretching may decrease acute muscular fatigue in ballet dancers. [ABSTRACT FROM AUTHOR]

Multiple variations of the deadlift/hip hinge exercise can be executed using the hexagonal (hex) bar with each variation differentiated, for instance, by starting knee and torso angles while maintaining a constant hip angle. These variations would plausibly accompany alterations to the overall electromyography (EMG) profile; however, no data exists to objectively substantiate these effects. PURPOSE: To examine and compare the muscle activation patterns of the biceps femoris, rectus femoris, and erector spinae during three deadlift/hip and knee extension exercise variations using the hex bar. METHODS: Twenty resistance trained male and female subjects performed deadlift variations using a hex bar in three different starting knee flexion positions: 128.4 ± 8.5 degrees (similar to an elevated Romanian Deadlift), 111.9 ± 8.7 degrees (similar to a conventional elevated deadlift), and 98.3 ± 6.5 degrees (conventional hexagonal bar deadlift). Subjects performed three repetitions at 75% of their three-repetition maximum at a 1-2 second tempo (concentric-eccentric). Electromyography sensors were placed on the dominant biceps femoris, rectus femoris, and lumbar erector spinae of each subject. A one-way repeated measures ANOVA was used to detect significant differences in mean and peak EMG values normalized to maximum voluntary isometric contraction (MVIC) (p<0.05). RESULTS: As knee flexion increased at the starting position, mean activation of the rectus femoris increased (24.7±21.5 to 35.5±25.4 to 62.1±31.3% MVIC, p<0.001), while the biceps femoris (40.6±17.9 to 34.0±16.4 to 28.1±14.5% MVIC, p=0.003) and erector spinae (73.0±27.6 to 65.9±34.4 to 54.9±32.5% MVIC, p=0.009) activation decreased. Peak activations of the rectus femoris also increased (46.9±33.0 to 60.9±38.7 to 99.3±41.6% MVIC, p<0.001) while decreasing in the erector spinae (118.6±47.1 to 105.9±49.4 to 89.1±40.1% MVIC, p=0.008). The rectus femoris experienced the greatest mean differences of the three muscles. CONCLUSIONS: Coaches and practitioners should consider the muscular goals when adjusting the starting position of a hexagonal bar deadlift as posterior chain recruitment diminished as knee flexion increased. Rectus femoris activation increased with increased knee flexion. [ABSTRACT FROM AUTHOR]

We eagerly await the results of prospective trials in ECCO SB 2 sb R for patients with respiratory failure, which may inform the safety and effectiveness of ECCO SB 2 sb R in specific patient populations. We read the article by Bromberger et al ([1]) with interest and applaud the authors for outstanding outcomes in a 26-patient cohort with acute severe asthma who received extracorporeal life support (ECLS) for hypercapnic respiratory failure. The ECCO SB 2 sb R device used in these trials features a membrane lung cross-sectional area of 0.59 m SP 2 sp , blood flow rates between 0.35 and 0.55 L/min, and a 15.5-Fr single-site, dual-lumen cannula. [Extracted from the article]

BACKGROUND Mohs micrographic surgery (MMS) continues to become a more common and accepted treatment for lentigo maligna (LM) and lentigo maligna melanoma (LMM). The primary difficulty encountered lies in the accurate identification of atypical single melanocytes to determine tumor-free margins. Numerous methods have been used to better visualize single melanocytes, with varying results. We present our experience using Mel-5 immunostaining in MMS of LM and LMM. METHODS Two hundred patients with primary or recurrent LM or LMM were treated using MMS from 1999 to 2003 at the University of Minnesota. The initial clinical margins were determined by Wood's light examination, and an initial debulk specimen was taken and sent for formalin fixation and later reviewed by a dermatopathologist. The first Mohs layer was then taken, and staining with hemotoxylin and eosin as well as Mel-5 immunostaining was performed. All patients were followed up to evaluate for recurrence, with a mean follow-up time of 38.4 months. RESULTS Of the 200 patients treated, only one recurrence was noted. This patient had been treated with excision followed by radiation before MMS. Use of Mel-5 immunostaining added approximately 40 minutes to each stage. Use of the Autostainer Immunostaining System (DAKO, Carpenterina, CA, USA) shortened the added time to 20 minutes. CONCLUSIONS MMS with Mel-5 immunostaining yielded excellent results in the treatment of LM and LMM, with only one recurrence noted in 200 patients. When an automated immunostainer was used, minimal time was added to each Mohs stage. [ABSTRACT FROM AUTHOR]

Device complication rates were analyzed in the Regulatory and Quality Assurance departments of Thermage, Inc., Hayward, CA, USA, in consultation with Dr. Whitney D. Tope. Corrective treatment in the case study was performed at the Dermatology Surgery and Laser Center, White Plains, NY. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE. As the number of patients with implantable cardiac devices escalates, inadvertent electromagnetic interference (EMI) by electrosurgery carries increasing concern for patient safety. Given the trend for dermatologic care delivery by nonphysician providers, supervising physicians must carefully consider the adequacy of perioperative evaluation in elective or cosmetic settings. Rapidly evolving technology also calls into question potential EMI of new therapeutic modalities (radiofrequency resurfacing, electrochemotherapy, and endovenous ablation). The most recently published recommendations (1998) for care of dermatologic patients with cardiac devices do not differ significantly from guidelines proposed in 1975. These recommendations, based on complications experienced during noncutaneous surgery, are exceedingly conservative and do not take into consideration the different electrosurgical modalities and varying degrees of EMI risk. In addition, modern cardiac devices have evolved significantly with increased sophistication in protection from EMI. A survey of dermatologic surgeons demonstrated low compliance with these existing guidelines. METHODS, RESULTS, AND CONCLUSIONS. Based on a review of the literature and current electrosurgical and cardiac devices, we discuss the potential impact of conventional dermatologic electro-surgery and new technologies. We propose that new perioperative guidelines are needed to provide appropriate safety, facile implementation, and cost-effective care for patients with modern implantable cardiac devices. [ABSTRACT FROM AUTHOR]

Microporous polysaccharide hemospheres consist of controlled-porosity spherical particles manufactured from bioinert plant polysaccharide. Microporous polysaccharide hemospheres facilitate hemostasis by rapidly absorbing the fluid component of blood, concentrating platelets and clotting factors to accelerate blood clotting. The objective was to compare a microporous polysaccharide hemosphere bandage and electrocautery in achieving hemostasis. Twenty-four patients with a total of 48 stages of Mohs micrographic surgery were included. Patients were stratified by whether or not they were taking anticoagulant medications. Within each group, patients were randomized to receive either the microporous polysaccharide hemosphere bandage or electrocautery. Outcomes included bleeding through the dressing (early time point) and active bleeding upon dressing removal (late time point). Nineteen patients not taking anticoagulants had 40 stages, of which 18 received the study bandage and 22 received electrocautery. The remaining 5 patients on anticoagulants had 8 stages, of which 4 received the study bandage and 4 received electrocautery. In both total and subgroup analysis, there was a higher incidence of bleeding through the dressing with the study bandage (p<0.05), but no increase in the incidence of active bleeding upon dressing removal (p>0.05). The microporous polysaccharide hemosphere study bandage had an increased incidence of bleeding through the dressing compared to electrocautery, but did not have an increased incidence of active bleeding upon dressing removal. THE MICROPOROUS POLYSACCHARID HEMOSPHERES USED IN THE TRIAL WERE SUPPLIED BY THE MANUFACTURER, MEDATOR, INC. WHITNEY D. TOPE IS A MEMBER OF THE MEDICAL ADVISORY BOARD FOR MEDATOR, INC AND HAS RECEIVED STOCK OPTIONS FOR THIS SERVICE. [ABSTRACT FROM AUTHOR]

Systemic retinoids possess significant benefits in cutaneous malignancy chemoprevention; however, retinoids have been associated with excessive granulation tissue and hypertrophic scarring. The objective of this study was to assess wound healing outcomes in organ transplant recipients, both with and without the concomitant use of systemic acitretin chemoprophylaxis. Twenty-nine immunosuppressed organ transplant recipients underwent treatment of basal cell or squamous cell carcinoma by Mohs or excisional surgery, with a total of 85 wounds. Wounds were evaluated postoperatively at early (average 12.9 days) and late (average 75.8 days) time points. Endpoints for all wounds included infection, hypertrophic granulation tissue, and hypertrophic scarring. Reconstructed wounds were also evaluated for dehiscence. Eleven patients taking oral acitretin had 41 wounds, of which 33 were reconstructed and 8 healed by second intention. The 18 patients not taking acitretin (control group) had a total of 44 wounds, of which 33 were reconstructed and 11 healed by second intention. There were no statistically significant differences between the acitretin group and the control group in the incidences of infection, dehiscence, hypertrophic granulation tissue, or hypertrophic scarring at early or late evaluation points. Systemic acitretin chemoprophylaxis does not appear to increase the risk of wound healing complications in organ transplant recipients. STEPHEN R. TAN, MD, FRCPC, AND WHITNEY D. TOPE, MPHIL, MD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [ABSTRACT FROM AUTHOR]

Background. Well-defined histopathologic criteria exist to distinguish actinic keratosis (AK) from superficial basal cell carcinoma (BCC). A similar morphology of downwardly budding dysplastic keratinocytes may occur in both entities, creating potential for errors in diagnosis. A marker that could reliably distinguish these two lesions would overcome this difficulty in diagnosis. Objective. To investigate whether Ber-EP4 staining is useful in distinguishing AK from superficial BCC, and to determine whether AK exhibits a cellular phenotype that is more consistent with BCC or squamous cell carcinoma (SCC). Methods. We subjected tissue sections from superficial BCC, AK, and squamous intraepithelial neoplasia (SIN) demonstrating epidermal budding to immunohistochemical staining with monoclonal antibody Ber-EP4. Results. Abnormal keratinocytes in all specimens of superficial BCC (5 of 5) were Ber-EP4 positive; all AK (10 of 10) and SIN (8 of 8) were Ber-EP4 negative. Conclusion. Ber-EP4 staining reliably distinguishes AK from superficial BCC. The lack of Ber-EP4 staining of AK supports the currently accepted pathogenetic dogma that SIN and SCC arise from AK, but BCC does not. [ABSTRACT FROM AUTHOR]

Background. Eruptive vellus hair cysts (EVHC) frequently resist a variety of treatment modalities. While pulsed carbon dioxide (CO2) laser has been used effectively for facial EVHC, this laser presents significant risks for hypertrophic scarring when used on truncal sites. Due to absorption of 2940 nm energy by both tissue water and protein, the erbium:yttrium-aluminum-garnet (Er:YAG) laser ablates more cleanly and creates less residual thermal injury in the wound bed. This laser might prove efficacious and safe in treating nonfacial EVHC. Objective. To assess treatment efficacy and wound healing after Er:YAG laser ablation of EVHC. Methods. Two patients with 32 truncal EVHC were treated with pulsed Er:YAG laser using a drilling technique followed by second intention healing. Results. Laser treatment sites healed without permanent dyspigmentation or hypertrophic scarring. No lesion recurrence was observed. Conclusion. Er:YAG laser ablation is an effective method for treating EVHC at anatomic sites prone to hypertrophic scar formation. [ABSTRACT FROM AUTHOR]

Background. A novel radio frequency multi-electrode surgical (MES) device has produced minimal residual thermal collagen damage (RTCD) and rapid healing in treating articular cartilage. Objective. To assess the immediate tissue effects of the MES device on human skin. Methods. Specimens of ex vivo human skin were subjected to 1 to 3 passes of the device at 3 voltage settings, then processed for routine and polarized light microscopy. The degree of tissue ablation, amount of RTCD, and level of follicular injury were assessed. Results. Epidermal ablation did not occur; epidermal removal correlated with manual debridement after the first passes. Dermal ablation was not readily discernable even after 2 or 3 passes. The thickness of RTCD tended to increase with increased pass number. The mean thickness of this zone of damaged collagen measured 24–53 μ after 1, 63–83 μ after 2, and 80–97 μ after 3 passes, respectively. For a given number of passes, the thickness of the zone of RTCD did not consistently change with increasing voltage applied (86, 108, and 139 V). The small number of samples did not enable meaningful statistical analysis of these observations. In samples with pilosebaceous units, the electrosurgical keratinocyte injury extended down the follicular epithelium, but never beyond the level of the infundibulum. Conclusions. These findings suggest the MES device produces immediate tissue effects favorable for effective cutaneous resurfacing and rapid postoperative wound healing. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare no conflicts of interest.

Background: The Affordable Care Act has been associated with increased Medicaid coverage for childbirth among low-income US women. We hypothesized that Medicaid expansion was associated with increased use of labor neuraxial analgesia., Methods: We performed a cross-sectional analysis of US women with singleton live births who underwent vaginal delivery or intrapartum cesarean delivery between 2009 and 2017. Data were sourced from births in 26 US states that used the 2003 Revised US Birth Certificate. Difference-in-difference linear probability models were used to compare changes in the prevalence of neuraxial labor analgesia in 15 expansion and 11 nonexpansion states before and after Medicaid expansion. Models were adjusted for potential maternal and obstetric confounders with standard errors clustered at the state level., Results: The study sample included 5,703,371 births from 15 expansion states and 5,582,689 births from 11 nonexpansion states. In the preexpansion period, the overall rate of neuraxial analgesia in expansion and nonexpansion states was 73.2% vs 76.3%. Compared with the preexpansion period, the rate of neuraxial analgesia increased in the postexpansion period by 1.7% in expansion states (95% CI, 1.6-1.8) and 0.9% (95% CI, 0.9-1.0) in nonexpansion states. The adjusted difference-in-difference estimate comparing expansion and nonexpansion states was 0.47% points (95% CI, -0.63 to 1.57; P = .39)., Conclusions: Medicaid expansion was not associated with an increase in the rate of neuraxial labor analgesia in expansion states compared to the change in nonexpansion states over the same time period. Increasing Medicaid eligibility alone may be insufficient to increase the rate of neuraxial labor analgesia., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

The purpose of this study was to look for a possible explanation for the variation in the incidence rate of melanoma among counties in Washington state. We used data from the Washington State Cancer Registry (WSCR), the Cancer Center at PeaceHealth St. Joseph Hospital in Whatcom County, and the Surveillance, Epidemiology, and End Results registry to get information on melanoma incidence. Demographic and migration records were obtained from the US Census Bureau, the Washington State Department of Licensing (DOL), and the US Internal Revenue Service (IRS). A number of different analytic techniques were used to address our research question, including a multiple regression analysis, time trend comparisons, and an analysis of birthplace data of melanoma patients in Whatcom county. We found a significant association between migration rate from the Southwest (SW) USA and melanoma incidence (P<0.001). Plots of time trend show that melanoma rates track with migration from the SW. In Whatcom county, almost half of all residents were born outside of Washington state, but they accounted for about 70% of all melanoma cases. Our analyses suggest that migration from the SW is an important factor in explaining the variation in melanoma rate among counties in Washington.

Xeroderma pigmentosum (XP) is a group of rare inherited human neurocutaneous diseases, and the group C (XPC) is the major group of patients with XP in Europe, North America, and South America. Current molecular diagnostic methods for XP require specialized, expensive, and time-consuming UV sensitivity and DNA repair assays followed by gene sequencing. To determine whether immunohistochemistry (IHC) would be a robust alternative method to diagnose patients with XPC, we stained sections of paraffin-embedded skin biopsies for XPC by IHC, using 69 archived blocks from confirmed or clinically suspect patients with XPA, XPC, XPD, XPE, and without XP. We found that XPC expression was strong in all skin biopsies from patients without (14 of 14) and other patients with XP (4 of 4), whereas XPC expression was lost in all biopsies from confirmed XPC patients (29 of 29). Patches of strong XPC signal could be detected in sun-damaged skin, squamous and basal cell carcinomas from patients with XPC that colocalized with strong expression of p53 and Ki-67. Patients with XPC can therefore be diagnosed by IHC from paraffin-embedded skin biopsies from regions of skin that are without sun damage or sun-induced tumors. IHC is therefore a robust alternative method to diagnose patients with XPC. This fast and inexpensive method should increase the options for the diagnosis of patients with XPC from paraffin-embedded skin biopsies and could be developed for other complementation groups.

We studied 12 consecutive neonates placed on venoarterial extracorporeal membrane oxygenation (ECMO) in 2004-2005. Activated clotting times (ACT) and anti-factor Xa levels were measured, and the corresponding heparin drip rate was noted. The mean heparin drip rate was 42.2 +/- 10.9 (SD) U/kg/hour (range 20.0-69.5 U/kg/hour). There were 55 simultaneous ACT and anti-factor Xa samples drawn. The mean ACT was 167 +/- 20 seconds (range 128-227 seconds). There was no correlation between ACT levels and heparin dose (r = 0.21; p = 0.12). The mean anti-factor Xa activities were 0.73 +/- 0.19 U/ml (range 0.1-1.0 U/ml). There was a correlation (r = 0.75; p < 0.0001) between anti-factor Xa and heparin dose. We also examined the effect of day on ECMO on heparin drip rate, ACT, and anti-factor Xa. There was no correlation between day on ECMO and either heparin drip rate (r = 0.21, p = 0.12) or ACT (r = 0.002, p = 0.99). However, there was a positive correlation (r = 0.46, p < 0.0005) between day on ECMO and anti-factor Xa activities. In these neonatal patients on venoarterial ECMO, ACT was not a reliable indicator of heparin effect. Furthermore, the increase in anti-factor Xa levels with time on ECMO suggests that heparin accumulates and/or that anti-thrombin III levels decrease with time on ECMO.