We studied the variable effects of norepinephrine infusion on cardiac output in postoperative cardiac surgical patients in whom norepinephrine increased mean arterial pressure. We hypothesized that ...the directional change in cardiac output would be determined by baseline cardiac function, as quantified by stroke volume variation, and the subsequent changes in mean systemic filling pressure and vasomotor tone.
Intervention study.
ICU of a university hospital.
Sixteen mechanically ventilated postoperative cardiac surgery patients.
Inspiratory holds were performed at baseline-1, during increased norepinephrine infusion, and baseline-2 conditions.
We measured mean arterial pressure, heart rate, central venous pressure, cardiac output, stroke volume variation and, with use of inspiratory hold maneuvers, mean systemic filling pressure, then calculated resistance for venous return and systemic vascular resistance. Increasing norepinephrine by 0.04 ± 0.02 μg·kg·min increased mean arterial pressure 20 mm Hg in all patients. Cardiac output decreased in ten and increased in six patients. In all patients mean systemic filling pressure, systemic vascular resistance and resistance for venous return increased and stroke volume variation decreased. Resistance for venous return and systemic vascular resistance increased more (p = 0.019 and p = 0.002) in the patients with a cardiac output decrease. Heart rate decreased in the patients with a cardiac output decrease (p = 0.002) and was unchanged in the patients with a cardiac output increase. Baseline stroke volume variation was higher in those in whom cardiac output increased (14.4 ± 4.2% vs. 9.1 ± 2.4%, p = 0.012). Stroke volume variation >8.7% predicted the increase in cardiac output to norepinephrine (area under the receiver operating characteristic curve 0.900).
The change in cardiac output induced by norepinephrine is determined by the balance of volume recruitment (increase in mean systemic filling pressure), change in resistance for venous return, and baseline heart function. Furthermore, the response of cardiac output on norepinephrine can be predicted by baseline stroke volume variation.
Purpose
To assess the level of agreement between different bedside estimates of effective circulating blood volume—mean systemic filling pressure (Pmsf), arm equilibrium pressure (Parm) and model ...analog (Pmsa)—in ICU patients.
Methods
Eleven mechanically ventilated postoperative cardiac surgery patients were studied. Sequential measures were made in the supine position, rotating the bed to a 30° head-up tilt and after fluid loading (500 ml colloid). During each condition four inspiratory hold maneuvers were done to determine Pmsf; arm stop-flow was created by inflating a cuff around the upper arm for 30 s to measure Parm, and Pmsa was estimated from a Guytonian model of the systemic circulation.
Results
Mean Pmsf, Parm and Pmsa across all three states were 20.9 ± 5.6, 19.8 ± 5.7 and 14.9 ± 4.0 mmHg, respectively. Bland-Altman analysis for the difference between Parm and Pmsf showed a non-significant bias of −1.0 ± 3.08 mmHg (
p
= 0.062), a coefficient of variation (COV) of 15 %, and limits of agreement (LOA) of −7.3 and 5.2 mmHg. For the difference between Pmsf and Pmsa we found a bias of −6.0 ± 3.1 mmHg (
p
< 0.001), COV 17 % and LOA −12.4 and 0.3 mmHg. Changes in Pmsf and Parm and in Pmsf and Pmsa were directionally concordant in response to head-up tilt and volume loading.
Conclusions
Parm and Pmsf are interchangeable in mechanically ventilated postoperative cardiac surgery patients. Changes in effective circulatory volume are tracked well by changes in Parm and Pmsa.
Abstract
Background
Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature ...is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO.
Methods
This was a sub-study of a multicenter (
N
= 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018–Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100–150·10
9
/L), moderate (50–100·10
9
/L) and severe (< 50·10
9
/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models.
Results
Of the 419 patients included, median platelet count at admission was 179·10
9
/L. During VA ECMO, almost all (
N
= 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (
N
= 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9–56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34–360).
Conclusions
Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding.
Trial registration
: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at
https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.
Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which ...heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT). However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome.
We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2-2.5 times baseline aPTT, 1.5-2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months.
We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO.
ClinicalTrials.gov NCT04536272 . Registered on 2 September 2020. Netherlands Trial Register NL7969.
Mean systemic filling pressure (Pmsf) can be measured at the bedside with minimally invasive monitoring in ventilator-dependent patients using inspiratory hold maneuvers (Pmsf(hold)) as the zero flow ...intercept of cardiac output (CO) to central venous pressure (CVP) relation. We compared Pmsf(hold) with arm vascular equilibrium pressure during vascular occlusion (Pmsf(arm)) and their ability to assess systemic vascular compliance (Csys) and stressed volume by intravascular fluid administration.
In mechanically ventilated postoperative cardiac surgery patients, inspiratory holds at varying airway pressures and arm stop-flow maneuvers were performed during normovolemia and after each of 10 sequential 50-mL bolus colloid infusions. We measured CVP, Pmsf(arm), stroke volume, and CO during fluid administration steps to construct CVP to CO (cardiac function) curves and Δvolume/ΔPmsf (compliance) curves. Pmsf(hold) was measured before and after fluid administration. Stressed volume was determined by extrapolating the Pmsf-volume curve to zero pressure intercept.
Fifteen patients were included. Pmsf(hold) and Pmsf(arm) were closely correlated. Csys was linear (64.3 ± 32.7 mL · mm Hg(-1), 0.97 ± 0.49 mL · mm Hg(-1) · kg(-1) predicted body weight). Stressed volume was estimated to be 1265 ± 541 mL (28.5% ± 15% predicted total blood volume). Cardiac function curves of patients with an increase of >12% to 500 mL volume extension (volume responsive) were steep, whereas the cardiac function curves of the remaining patients were flat.
Csys, stressed volume, and cardiac function curves can be determined at the bedside and can be used to characterize patients' hemodynamic status.
Purpose: This study reports on survival and health related quality of life (HRQOL) after extracorporeal membrane oxygenation (ECMO) treatment and the associated costs in the first year.
Materials and ...Methods: Prospective observational cohort study patients receiving ECMO in the intensive care unit during August 2017 and July 2019. We analyzed all healthcare costs in the first year after index admission. Follow-up included a HRQOL analysis using the EQ-5D-5L at 6 and 12 months.
Results: The study enrolled 428 patients with an ECMO run during their critical care admission. The one-year mortality was 50%. Follow up was available for 124 patients at 12 months. Survivors reported a favorable mean HRQOL (utility) of 0.71 (scale 0–1) at 12 months of 0.77. The overall health status (VAS, scale 0–100) was reported as 73.6 at 12 months. Mean total costs during the first year were $204,513 ± 211,590 with hospital costs as the major factor contributing to the total costs. Follow up costs were $53,752 ± 65,051 and costs of absenteeism were $7317 ± 17,036.
Conclusions: At one year after hospital admission requiring ECMO the health-related quality of life is favorable with substantial costs but considering the survival might be acceptable. However, our results are limited by loss of follow up. So it may be possible that only the best-recovered patients returned their questionnaires. This potential bias might lead to higher costs and worse HRQOL in a real-life scenario.
•One year costs after ICU admission with extracorporeal membrane oxygenation are high.•Hospital costs are the major factor contributing to the total costs.•Health related quality of life is favorable and comparable to the general population.
Extracorporeal life support (ECLS) is used to support the cardiorespiratory function in case of severe cardiac and/or respiratory failure in critically ill patients. According to the ELSO guidelines ...ECLS should be considered when estimated mortality risk approximates 80%. ECLS seems an efficient therapy in terms of survival benefit, but no undisputed evidence is delivered yet. The aim of the study is to assess the health-related quality of life after ECLS treatment and its cost effectiveness.
We will perform a prospective observational cohort study. All adult patients who receive ECLS in the participating centers will be included. Exclusion criteria are patients in whom the ECLS is only used to bridge a procedure (like a high risk percutaneous coronary intervention or surgery) or the absence of informed consent. Data collection includes patient characteristics and data specific for ECLS treatment. Severity of illness and mortality risk is measured as precisely as possible using measurements for the appropriate age group and organ failure. For analyses on survival patients will act as their own control as we compare the actual survival with the estimated mortality on initiation of ECLS if conservative treatment would have been continued. Survivors are asked to complete validated questionnaires on health related quality of life (EQ5D-5 L) and on medical consumption and productivity losses (iMTA/iPCQ) at 6 and 12 months. Also the health related quality of life 1 month prior to ECLS initiation will be obtained by a questionnaire, if needed provided by relatives. With an estimated overall survival of 62% 210 patients need to be recruited to make a statement on cost effectiveness for all ECLS indications.
If our hypothesis that ECLS treatment is cost-effective is confirmed by this prospective study this could lead to an even broader use of ECLS treatment.
The trial is registered at ( NCT02837419 ) registration date July 19, 2016 and with the Dutch trial register, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6599.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Mean systemic filling pressure (Pmsf) can be determined at the bedside by measuring central venous pressure (Pcv) and cardiac output (CO) during inspiratory hold maneuvers. Critical closing pressure ...(Pcc) can be determined using the same method measuring arterial pressure (Pa) and CO. If Pcc > Pmsf, there is then a vascular waterfall. In this study, we assessed the existence of a waterfall and its implications for the calculation of vascular resistances by determining Pmsf and Pcc at the bedside.
In 10 mechanically ventilated postcardiac surgery patients, inspiratory hold maneuvers were performed, transiently increasing Pcv and decreasing Pa and CO to 4 different steady-state levels. For each patient, values of Pcv and CO were plotted in a venous return curve to determine Pmsf. Similarly, Pcc was determined with a ventricular output curve plotted for Pa and CO. Measurements were performed in each patient before and after volume expansion with 0.5 L colloid, and vascular resistances were calculated.
For every patient, the relationship between the 4 measurements of Pcv and CO and of Pa and CO was linear. Baseline Pmsf was 18.7 ± 4.0 mm Hg (mean ± SD) and differed significantly from Pcc 45.5 ± 11.1 mm Hg (P < 0.0001). The difference of Pcc and Pmsf was 26.8 ± 10.7 mm Hg, indicating the presence of a systemic vascular waterfall. Volume expansion increased Pmsf (26.3 ± 3.2 mm Hg), Pcc (51.5 ± 9.0 mm Hg), and CO (5.5 ± 1.8 to 6.8 ± 1.8 L · min(-1)). Arterial (upstream of Pcc) and venous (downstream of Pmsf) vascular resistance were 8.27 ± 4.45 and 2.75 ± 1.23 mm Hg · min · L(-1); the sum of both (11.01 mm Hg · min · L(-1)) was significantly different from total systemic vascular resistance (16.56 ± 8.57 mm Hg · min · L(-1); P = 0.005). Arterial resistance was related to total resistance.
Vascular pressure gradients in cardiac surgery patients suggest the presence of a vascular waterfall phenomenon, which is not affected by CO. Thus, measures of total systemic vascular resistance may become irrelevant in assessing systemic vasomotor tone.
OBJECTIVE:To measure the relationship between blood flow and central venous pressure (Pcv) and to estimate mean systemic filling pressure (Pmsf), circulatory compliance, and stressed volume in ...patients in the intensive care unit.
DESIGN:Intervention study.
SETTING:Intensive care unit of a university hospital.
PATIENTS:Twelve mechanically ventilated postoperative cardiac surgery patients.
INTERVENTIONS:Inspiratory holds were performed during normovolemia in supine position (baseline), relative hypovolemia by placing the patients in 30 degree head-up position (hypo), and relative hypervolemia by volume loading with 0.5 L colloid (hyper).
MEASUREMENTS AND MAIN RESULTS:We measured the relationship between blood flow and Pcv using 12-second inspiratory-hold maneuvers transiently increasing Pcv to three different steady-state levels and monitored the resultant blood flow via the pulse contour method during the last 3 seconds. The Pcv to blood flow relation was linear for all measurements with a slope unaltered by relative volume status. Pmsf decreased with hypo and increased with hyper (18.8 ± 4.5 mm Hg, to 14.5 ± 3.0 mm Hg, to 29.1 ± 5.2 mm Hg baseline, hypo, hyper, respectively, p < 0.05). Baseline total circulatory compliance was 0.98 mL·mm Hg·kg and stressed volume was 1677 mL.
CONCLUSIONS:Pmsf can be determined in intensive care patients with an intact circulation with use of inspiratory pause procedures, making serial measures of circulatory compliance and circulatory stressed volume feasible.
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