Changes in Red Blood Cell Properties and Platelet Function during Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is associated with frequent hemorrhagic and thromboembolic complications. The multiple effects of ECMO include inflammatory response on contact with the circuit; hemolysis acquired von Willebrand syndrome likely affects the function of red blood cells (RBC) and platelets. The aim of this prospective observational study was to analyze RBC aggregation and elongation (deformability) and platelet aggregation in the first week of ECMO. Sixteen patients were included. Blood samples were taken prior to initiation of ECMO and on days 1, 2, 3, 5, and 7. RBC aggregation and elongation were analyzed using the laser-assisted optical rotational red cell analyzer (Lorrca). Upstroke, top, and amplitude as indices of aggregation showed significant time effects. RBC elongation was not affected at low shear stress. At high shear stress there was an increase in the elongation index at day 2 (p = 0.004), followed by a decrease. Platelet function was analyzed using multiple electrode aggregometry (Multiplate®). In pairwise comparison in the days 1–7 to the value prior to ECMO there was no significant difference in platelet aggregation by any of the three agonists (ADP p = 0.61; TRAP p = 0.77; Ristocetin p = 0.25). This implies that the rheology of RBCs seemed to be more affected by ECMO than platelets. Especially the red blood cell deformability continues to decline at higher shear stress

Hospital Costs of Extracorporeal Membrane Oxygenation in Adults:A Systematic Review

BACKGROUND: Costs associated with extracorporeal membrane oxygenation (ECMO) are an important factor in establishing cost effectiveness. In this systematic review, we aimed to determine the total hospital costs of ECMO for adults. METHODS: The literature was retrieved from the PubMed/MEDLINE, EMBASE, and Web of Science databases from inception to 4 March 2020 using the search terms ‘extracorporeal membrane oxygenation’ combined with ‘costs’; similar terms or phrases were then added to the search, i.e. ‘Extracorporeal Life Support’ or ‘ECMO’ or ‘ECLS’ combined with ‘costs’. We included any type of study (e.g. randomized trial or observational cohort) evaluating hospital costs of ECMO in adults (age ≥18 years). RESULTS: A total of 1768 unique articles were retrieved during our search. We assessed 74 full-text articles for eligibility, of which 14 articles were selected for inclusion in this review; six papers were from the US, five were from Europe, and one each from Japan, Australia, and Taiwan. The sample sizes ranged from 16 to 18,684 patients. One paper exclusively used prospective cost data collection, while all other papers used retrospective data collection. Five papers reported charges instead of costs. There was large variation in hospital costs, ranging from US$22,305 to US$334,608 (2019 values), largely depending on the indication for ECMO support and location. The highest reported costs were for lung transplant recipients who were receiving ECMO support in the US, and the lowest reported costs were for extracorporeal cardiopulmonary resuscitation patients presenting with non-shockable rhythm in Japan. The additional costs of ECMO patients compared with non-ECMO patients varied between US$2518 and US$200,658. Personnel costs varied between 11 and 52% of the total amount. CONCLUSIONS: ECMO therapy is an advanced and expensive technology, although reported costs differ considerably depending on ECMO indication and whether charges or costs are measured. Combined with the ongoing gathering of outcome data, cost effectiveness per ECMO indication could be determined in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41669-021-00272-9

Hemorrhagic complications during extracorporeal membrane oxygenation - The role of anticoagulation and platelets

PURPOSE: Hemorrhagic complications during extracorporeal membrane oxygenation are frequent and have a negative impact on outcome. We studied the association between activated partial thromboplastin time or platelet count and the occurrence of hemorrhagic complications. The secondary objective was to determine risk factors for hemorrhagic complications. METHODS: Retrospective cohort study in a single-center Dutch university hospital. We included all adult patients on extracorporeal membrane oxygenation admitted to the intensive care unit between 2010 and 2017. RESULTS: We included 164 consecutive patients of which 73 (45%) had a hemorrhagic complication. The most prevalent hemorrhagic complications were surgical site (62%) and cannula site bleeding (18%). Survival to discharge was 67% in the patients without a hemorrhagic complication and 33% in the patients with hemorrhagic complications (p < .01). A higher activated partial thromboplastin time in the 24 h prior was associated with the occurrence of hemorrhagic complications (adjusted hazard ratio per 10 s increase 1.14; (95% CI 1.05-1.24). Venoarterial extracorporeal membrane oxygenation, duration of support, and higher activated partial thromboplastin time were risk factors for the occurrence of hemorrhagic complications. CONCLUSIONS: Higher activated partial thromboplastin time is associated with the occurrence of hemorrhagic complications

Coping strategies, anxiety and depressive symptoms in family members of patients treated with extracorporeal membrane oxygenation:A prospective cohort study

BACKGROUND: Family members of patients treated with Extracorporeal Membrane Oxygenation (ECMO) during an Intensive Care Unit (ICU) stay are at risk of developing symptoms of anxiety, depression and Post-Traumatic Stress Disorder (PTSD). Coping strategies used by family members may play an important role in the severity of some of these symptoms.OBJECTIVES: The primary aim of this study was to describe coping strategies used by family members of ECMO-treated patients during ICU admission and recovery period. The secondary aim was to explore the course of the symptoms anxiety, depression, PTSD, and Health Related Quality Of Life (HRQOL) over time.METHODS: In this single-center prospective longitudinal study, validated questionnaires were used to measure coping strategies, symptoms of anxiety, depression and PTSD, and HRQOL in family members of ECMO-treated patients directly after the start of ECMO and at one and six months after the start of ECMO.RESULTS: Family members (n = 26) mainly used problem-focused coping strategies. Symptoms of anxiety appeared to be most present during treatment but decreased over time, as did symptoms of depression and PTSD. HRQOL was severely affected, especially in the mental domain, and did not improve over time.CONCLUSION: In family members of ECMO-treated patients, problem-focused coping mechanisms were most prominent. Psychological functioning was impaired on admission but improved over time, although a mild reaction to stress remained.</p

How central obesity influences intra-abdominal pressure:a prospective, observational study in cardiothoracic surgical patients

Background: Intra-abdominal hypertension (IAH) is frequently present in critically ill patients and is an independent predictor for mortality. Better recognition of clinically important thresholds is necessary. Increased intra-abdominal pressure (IAP) is associated with renal dysfunction, and renal failure is one of the most consistently described organ dysfunctions associated with IAH. Obesity is also associated with kidney injury. The underlying mechanisms are not yet fully understood. Increased IAP may be a link in this association. The aim of this study was firstly to find the range in values of intra-abdominal pressure (IAP) in cardiothoracic surgery patients a secondly to investigate the relationship between central obesity, body mass index (BMI) and IAP and thirdly to investigate the relationship between IAP, inflammation and renal function in this population. Methods: Consecutive adult patients admitted to the cardiothoracic unit of the intensive care unit (ICU) after undergoing elective cardiothoracic surgery were included in this prospective, observational study. C-reactive protein (CRP) as a marker of inflammation and serum creatinine as a marker of renal function were measured pre- and postoperatively. Estimated glomerular filtration rates were calculated pre-and postoperatively. BMI was calculated. Waist circumference (WC), hip circumference (HC) and transvesical IAP were measured once directly after admission to the ICU postoperatively. Waist/ hip ratio (WHR) was calculated (WC divided by HC). Three definitions of central obesity were used. Central obesity was defined according to WC, WHR or median WHR. Results: In total, 186 patients undergoing cardiothoracic surgery were included. Mean IAP was 9.1 mmHg (SD 4.4). IAP = 12 mmHg was observed in 50 patients (26.9 %). IAP > 20 mmHg was measured in 4 patients (2.2 %). There was a positive correlation between IAP and BMI (r(2) = 0.05, p = 0.003). Correlations between IAP and WC (r(2) = 0.02, p = 0.054) and between IAP and WHR (r(2) = 0.01, p = 0.173) were not significant. There were no correlations between pre-or postoperative CRP and IAP (r(2) = 2.3 x 10(-4), p = 0.839 and r(2) = 0.013, p = 0.117, respectively). In obese patients postoperative CRP was significantly higher than in non-obese patients (p = 0.034). There were no correlations between pre-operative serum creatinine and IAP (r(2) = 3.3 x 10(-5), p = 0.938) or postoperative serum creatinine and IAP (r(2) = 0.003, p = 0.491). Conclusions: The range in IAP in patients undergoing cardiothoracic surgery was wide. There was a positive correlation between IAP and BMI. Correlations between IAP and indices for central obesity were not significant. In a multiple regression model BMI was a better predictor of IAP than WHR in this population. There were no correlations between pre- or postoperative CRP and IAP. Furthermore, this study did not find evidence for a relation between IAP and pre- and postoperative serum creatinine

Ganciclovir Therapeutic Drug Monitoring:A Case Series

This paper presents three cases of immunocompromised patients for whom therapeutic drug monitoring (TDM) of ganciclovir in combination with cytomegalovirus (CMV) viral load measurement was used to guide treatment. The first patient is diagnosed with Thymoma A, the second is a heart transplant recipient and the third is an HIV positive patient. These patients were all diagnosed with CMV and treated with ganciclovir. Our case studies illustrate how TDM guided dosing can be helpful in the management of these complex cases.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

Long-term changes in dysnatremia incidence in the ICU: a shift from hyponatremia to hypernatremia

Background: Dysnatremia is associated with adverse outcome in critically ill patients. Changes in patients or treatment strategies may have affected the incidence of dysnatremia over time. We investigated long-term changes in the incidence of dysnatremia and analyzed its association with mortality. Methods: Over a 21-year period (1992–2012), all serum sodium measurements were analyzed retrospectively in two university hospital ICUs, up to day 28 of ICU admission for the presence of dysnatremia. The study period was divided into five periods. All serum sodium measurements were collected from the electronic databases of both ICUs. Serum sodium was measured at the clinical chemistry departments using standard methods. All sodium measurements were categorized in the following categories: 160 mmol/L. Mortality was determined at 90 days after ICU admission. Results: In 80,571 ICU patients, 913,272 serum sodium measurements were analyzed. A striking shift in the pattern of ICU-acquired dysnatremias was observed: The incidence of hyponatremia almost halved (47–25 %, p  155 mmol/L) increased dramatically over the years. On ICU day 10 this incidence was 0.7 % in the 1992–1996 period, compared to 6.3 % in the 2009–2012 period (p < 0.001). More severe dysnatremia was associated with significantly higher mortality throughout the 21-year study period (p < 0.001). Conclusions: In two large Dutch cohorts, we observed a marked shift in the incidence of dysnatremia from hyponatremia to hypernatremia over two decades. As hypernatremia was mostly ICU acquired, this strongly suggests changes in treatment as underlying causes. This shift may be related to the increased use of sodium-containing infusions, diuretics, and hydrocortisone. As ICU-acquired hypernatremia is largely iatrogenic, it should be—to an important extent—preventable, and its incidence may be considered as an indicator of quality of care. Strategies to prevent hypernatremia deserve more emphasis; therefore, we recommend that further study should be focused on interventions to prevent the occurrence of dysnatremias during ICU stay

Postoperative fluid retention after heart surgery is accompanied by a strongly positive sodium balance and a negative potassium balance

The conventional model on the distribution of electrolyte infusions states that water will distribute proportionally over both the intracellular (ICV) and extracellular (ECV) volumes, while potassium homes to the ICV and sodium to the ECV Therefore, total body potassium is the most accurate measure of ICV and thus potassium balances can be used to quantify changes in ICV In cardiothoracic patients admitted to the ICU we performed complementary balance studies to measure changes in ICV and ECV In 39 patients, fluid, sodium, potassium, and electrolyte-free water (EFW) balances were determined to detect changes in ICV and ECV Cumulatively over 4 days, these patients received a mean ± SE infusion of 14.0 ± 0.6 L containing 1465 ± 79 mmol sodium, 196 ± 11 mmol potassium and 2.1 ± 0.1 L EFW This resulted in strongly positive fluid (4.0 ± 0.6 L) and sodium (814 ± 75 mmol) balances but in negative potassium (-101 ± 14 mmol) and EFW (-1.1 ± 0.2 L) balances. We subsequently compared potassium balances (528 patients) and fluid balances (117 patients) between patients who were assigned to either a 4.0 or 4.5 mmol/L blood potassium target. Although fluid balances were similar in both groups, the additionally administered potassium (76 ± 23 mmol) in the higher target group was fully excreted by the kidneys (70 ± 23 mmol). These findings indicate that even in the context of rapid and profound volume expansion neither water nor potassium moves into the ICV

Incidence and risk factors of deep vein thrombosis after extracorporeal life support

Background: Deep vein thrombosis (DVT) after decannulation of extracorporeal life support (ECLS) is not uncommon. Moreover, the impact of anticoagulation and potential risk factors is unclear. Furthermore, it is unclear if cannula-associated DVT is more common in ECLS patients compared to critically ill patients without ECLS. Methods: All adult patients who were successfully weaned from ECLS and were screened for DVT following decannulation were included in this observational cohort study. The incidence of post-ECLS-DVT was assessed and the cannula-associated DVT rate was compared with that of patients without ECLS after central venous catheter (CVC) removal. The correlation between the level of anticoagulation, risk factors, and post-ECLS-DVT was determined. Results: We included 30 ECLS patients and 53 non-ECLS patients. DVT was found in 15 patients (50%) of which 10 patients had a DVT in a cannulated vein. No correlation between the level of anticoagulation and DVT was found. V-V ECLS mode was the only independent risk factor for post-ECLS-DVT (OR 5.5; 95%CI 1.16–26.41). We found no difference between the ECLS and non-ECLS cohorts regarding cannula-associated DVT rate (33% vs. 32%). Conclusion: Post-ECLS-DVT is a common finding that occurs in half of all patients supported with ECLS. The incidence of cannula-associated DVT was equal to CVC-associated DVT in critically ill patients without ECLS. V-V ECLS was an independent risk factor for post-ECLS-DVT

Extracorporeal Membrane Oxygenation in Patients With COVID-19:An International Multicenter Cohort Study

BACKGROUND: To report and compare the characteristics and outcomes of COVID-19 patients on extracorporeal membrane oxygenation (ECMO) to non-COVID-19 acute respiratory distress syndrome (ARDS) patients on ECMO. METHODS: We performed an international retrospective study of COVID-19 patients on ECMO from 13 intensive care units from March 1 to April 30, 2020. Demographic data, ECMO characteristics and clinical outcomes were collected. The primary outcome was to assess the complication rate and 28-day mortality; the secondary outcome was to compare patient and ECMO characteristics between COVID-19 patients on ECMO and non-COVID-19 related ARDS patients on ECMO (non-COVID-19; January 1, 2018 until July 31, 2019). RESULTS: During the study period 71 COVID-19 patients received ECMO, mostly veno-venous, for a median duration of 13 days (IQR 7-20). ECMO was initiated at 5 days (IQR 3-10) following invasive mechanical ventilation. Median PaO(2)/FiO(2) ratio prior to initiation of ECMO was similar in COVID-19 patients (58 mmHg [IQR 46-76]) and non-COVID-19 patients (53 mmHg [IQR 44-66]), the latter consisting of 48 patients. 28-day mortality was 37% in COVID-19 patients and 27% in non-COVID-19 patients. However, Kaplan-Meier curves showed that after a 100-day follow-up this non-significant difference resolves. Non-surviving COVID-19 patients were more acidotic prior to initiation ECMO, had a shorter ECMO run and fewer received muscle paralysis compared to survivors. CONCLUSIONS: No significant differences in outcomes were found between COVID-19 patients on ECMO and non-COVID-19 ARDS patients on ECMO. This suggests that ECMO could be considered as a supportive therapy in case of refractory respiratory failure in COVID-19