Feasibility of a pumpless extracorporeal respiratory assist device

Pasta for all: Abiomed Breethe extracorporeal membrane oxygenation system

The amount of extracorporeal carbon dioxide removal may influence respiratory drive in acute respiratory distress syndrome (ARDS) patients undergoing extracorporeal membrane oxygenation (ECMO). The authors evaluated the effects of different levels of extracorporeal carbon dioxide removal in patients recovering from severe ARDS undergoing pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA). The authors conducted a prospective, randomized, crossover study on eight spontaneously breathing ARDS patients undergoing venovenous ECMO since 28 ± 20 days. To modulate carbon dioxide extraction, ECMO gas flow (GF) was decreased from baseline resting protective conditions (i.e., GF100%, set to obtain pressure generated in the first 100 ms of inspiration against an occluded airway less than 2 cm H2O, respiratory rate less than or equal to 25 bpm, tidal volume less than 6 ml/kg, and peak airway pressure less than 25 cm H2O) to GF50%-GF25%-GF0% during both PSV and NAVA (random order for ventilation mode). Continuous recordings of airway pressure and flow and esophageal pressure were obtained and analyzed during all study phases. At higher levels of extracorporeal carbon dioxide extraction, pressure generated in the first 100 ms of inspiration against an occluded airway decreased from 2.8 ± 2.7 cm H2O (PSV, GF0%) and 3.0 ± 2.1 cm H2O (NAVA, GF0%) to 0.9 ± 0.5 cm H2O (PSV, GF100%) and 1.0 ± 0.8 cm H2O (NAVA, GF100%; P < 0.001) and patients' inspiratory muscle pressure passed from 8.5 ± 6.3 and 6.5 ± 5.5 cm H2O to 4.5 ± 3.1 and 4.2 ± 3.7 cm H2O (P < 0.001). In time, decreased inspiratory drive and effort determined by higher carbon dioxide extraction led to reduction of tidal volume from 6.6 ± 0.9 and 7.5 ± 1.2 ml/kg to 4.9 ± 0.8 and 5.3 ± 1.3 ml/kg (P < 0.001) and of peak airway pressure from 21 ± 3 and 25 ± 4 cm H2O to 21 ± 3 and 21 ± 5 cm H2O (P < 0.001). Finally, transpulmonary pressure linearly decreased when the amount of carbon dioxide extracted by ECMO increased (R = 0.823, P < 0.001). In patients recovering from ARDS undergoing ECMO, the amount of carbon dioxide removed by the artificial lung may influence spontaneous breathing. The effects of carbon dioxide removal on spontaneous breathing during the earlier acute phases of ARDS remain to be elucidated.

Seven-Day Artificial Lung Testing in an In-Parallel Configuration

Extracorporeal Carbon Dioxide Removal (ECCO2R): A Potential Perioperative Tool in End-Stage Lung Disease

To investigate the influence of continuous veno-venous hemofiltration (CVVH) on cardiac output (CO) value and parameters of hemodynamics monitored by transpulmonary thermodilution technique in critical patients. A prospective cohort study was conduced. Sixty-two critical patients admitted to intensive care unit (ICU) of Zunyi Medical College Affiliated Hospital from January 2011 to October 2015 were enrolled. All of the patients received CVVH through femoral vein puncture catheter. The CO value was monitored before CVVH operation, immediately after CVVH operation (8?centigrade normal saline was injected immediately after the output of blood from the arterial end), 5 minutes after operation, the time at the sudden interruption (press pause key after 10 minutes of operation) and resumed immediately, 15 minutes and 30 minutes after operation by pulse-indicated continuous cardiac output (PiCCO) with transpulmonary thermodilution method. The changes in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), and blood temperature were observed at all time points. From CVVH before start to 5 minutes thereafter, CO values were not significantly changed in patients, fluctuating in 6.96 (7.33, 8.67)-6.98 (6.43, 7.45) L/min. When CVVH was suddenly interrupted, CO value was immediately increased to the peak 8.04 (7.36, 8.77) L/min, which showed statistically significant difference as compared with other time points (all P < 0.01). Immediately after the CVVH recovery from interruption, the CO value dropped to 4.71 (4.14, 7.26) L/min, and it was significantly lower than those at other time points (all P < 0.01). With the CVVH recovery, the patients' CO value was gradually restored to the stable operation ahead of interruption [4.71 (4.14, 7.26)-6.85 (6.08, 7.26) L/min]. During CO monitoring, HR, MAP, CVP and blood temperature of the patients were at the same level, and no significant changes were founded. CVVH interruption of immediate PiCCO monitoring CO value were significantly increased, immediately after the CVVH recovery the CO value were significantly reduced, and the normal operation of CVVH did not affect the CO value monitoring. Hemodynamics and blood temperature of all patients were stable during CVVH.

Objective Toinvestigate the effects of carbon dioxide pneumoperitoneum on cardiovascular system by making use of arterial pressure waveform analysis( FloTrac/Vigileo system) to observe the change of heart function of patients undergoing laparoscopy cholecystotomy. Methods Forty patients scheduled for elective laparoscopy cholecystotomy were divided into two groups with 20 cases each by random sampling.Ventilatory capacity was fixed (tidal volume was 10 ml/kg, frequency was 12 times/min) in group A and adjusted to keep arterial carbon dioxide tension (PaCO2) and end expiration carbon dioxide tension(PETCO2)in normal range in group B. The parameters, such as mean arterial pressure (MAP), cardiac output(CO),stroke volume (SV), stroke volume variability (SVV), heart rate(HR), pulse oxygen saturation (SpO2),PETCO2, PaCO2 were recorded and analyzed. Results In group A:HR,MAP,CI,SVV,PaCO2 and PETCO2 were increased at 10,30 min after pneumoperitoneum (P ＜0.05 or ＜0.01),there was no significant difference in SVV between the end of pneumoperitoneum and 5 min after intubation [(8 ±2)% vs. (9 ±3 )%](P＞ 0.05 ) ,but HR, MAP, CI,SVI,PaCO2 and PETCO2 increased significantly (P＜ 0.05 or ＜ 0.01 ). In group B: HR, MAP, CI, SVI, PaCO2 and PETCO2 at 10,30 min after pneumoperitoneum were no changes (P ＞0.05 ), SVV was higher than that at 5 min after intubation (P ＜ 0.01 ), there was no significant difference in SVV between the end of pneumoperitoneum and 5 ain after intubation [(9 ± 2)% vs. ( 10 ± 2)%] (P ＞0.05 ). HR, CI, SVI, PaCO2, PETCO2 at 30 min after pneumoperitoneum and the end of pneumoperitoneun were significantly higher in group A than those in group B (P ＜ 0.05 or ＜ 0.01 ). Conclusions During carbon dioxide pneumoperitoneum, hypercapnia can increase MAP, HR, CO,SV significantly, and intra abdominal pressure can decrease preload by hindering the reflow of inferior vena cava and abdominal viscera veins. Arterial pressure waveform analysis can promptly reflect the effects of carbon dioxide pneumoperitoneum on cardiovascular system and be in favour of adjusting the respiration parameters and managing transfusion in laparoscopic surgery. Key words: Carbon dioxide; Pneumoperitoneum; Cardiovascular system; Arterial pressure waveform analysis

Prolonged hemodynamic stability during arteriovenous carbon dioxide removal for severe respiratory failure

Induction of general anaesthesia is often accompanied by hypotension. Standard haemodynamic monitoring during anaesthesia relies on intermittent blood pressure and heart rate. Continuous monitoring systemic blood pressure requires invasive or advanced modalities creating a barrier for obtaining important information of the circulation. The Peripheral Perfusion Index (PPI) is obtained non-invasively and continuously by standard photoplethysmography. We hypothesized that different patterns of changes in systemic haemodynamics during induction of general anaesthesia would be reflected in the PPI. Continuous values of PPI, stroke volume (SV), cardiac output (CO), and mean arterial pressure (MAP) were evaluated in 107 patients by either minimally invasive or non-invasive means in a mixed population of surgical patients. 2 min after induction of general anaesthesia relative changes of SV, CO, and MAP was compared to the relative changes of PPI. After induction total cohort mean(± st.dev.) MAP, SV, and CO decreased to 65(± 16)%, 74(± 18)%, and 63(± 16)% of baseline values. In the 38 patients where PPI decreased MAP was 57(± 14)%, SV was 63(± 18)%, and CO was 55(± 18)% of baseline values 2 min after induction. In the 69 patients where PPI increased the corresponding values were MAP 70(± 15)%, SV 80(± 16)%, and CO 68(± 17)% (all differences: p < 0,001). During induction of general anaesthesia changes in PPI discriminated between the degrees of reduction in blood pressure and algorithm derived cardiac stroke volume and -output. As such, the PPI has potential to be a simple and non-invasive indicator of the degree of post-induction haemodynamic changes.

To explore the changes of renal hemodynamic in dogs with endotoxemic shock (ES) and their potential roles in acute kidney injury (AKI). Canine endotoxic shock model was induced by an infusion of lipopolysaccharide of Escherichia coli through pulmonary artery catheter (PAC). Systemic hemodynamics and left renal blood flow (RBF) was monitored by PAC, pulse index continuous cardiac output (PiCCO) and ultrasonic blood flow meter. Blood and urine specimens were harvested timely for blood gas analysis, renal function tests and biochemical detection. Hemodynamics: CO and RBF fluctuated widely but without any significance (P > 0.05). The values of mean arterial pressure (MAP), systemic vascular resistance (SVR), renal vascular resistance (RVR) and 2-hour urine volume significantly decreased (all P < 0.05) while extravascular lung water (EVLW) increased markedly (P < 0.05). Renal function: There was a drop in CCr, urine osmotic pressure and an elevation in SCr and NAG. RBF was correlated positively with CO (R(2) = 0.630, P = 0.001) .However, it had no correlation with MAP (R(2) = 0.009, P = 0.758) . CCr was correlated positively with MAP (R(2) = 0.415, P = 0.003) . However, it had no correlation with RBF or CO (P > 0.05 ). The auto-regulation curve of GFR had a shift to the right. RBF is positively correlated with cardiac output in endotoxin shock. Renal pressure perfusion may decrease obviously without any noticeable change of renal flow perfusion. The shift of renal auto-regulation under pressure perfusion occurs at the early stage of septic shock.

Arteriovenous carbon dioxide removal (AVCO2R) as an alternative treatment for acute respiratory distress syndrome uses a low resistance gas exchanger in a simple arteriovenous shunt to achieve total CO2 removal and allow lung rest. We have previously shown in our clinically relevant LD40 ovine model of smoke/burn induced acute respiratory distress syndrome that AVCO2R allows significant decreases in respiratory rate, tidal volume, peak airway pressure, and FiO2, as compared with standard mechanical ventilation. In addition, we have shown in a prospective randomized outcomes study that AVCO2R increases ventilator free days, decreases ventilator dependent days, and significantly improves survival. The purpose of this study is to further define the limits of AVCO2R through hemodynamic augmentation and evaluation of peak end expiratory pressure (PEEP). Administration of an alpha agonist (phenylephrine) and a beta agonist (isoproterenol) increased mean arterial pressure (MAP) and cardiac output (CO), respectively. MAP increases ranged from 2.4% to 94.4% and CO increases ranged from 33% to 146%. Phenylephrine caused elevations in MAP (2.4-94.4%) and AVCO2R flow (9-67%), and CO never decreased more than 10%. Isoproterenol administration increased CO (33-146%), decreased MAP (9-54%), and decreased AVCO2R flow (11-42%). In a second group, PEEP was increased stepwise from 0 (baseline) to 20 cm H2O. Increasing PEEP did not result in significant hemodynamic changes (< 10% change from baseline PEEP) for MAP, CO, or AVCO2R flow. In conclusion, alpha agonist administration increased AVCO2R blood flow, whereas beta agonist administration decreased MAP and AVCO2R blood flow, despite CO elevation. Various levels of PEEP are well tolerated and thus allow a range of options during AVCO2R.

Purpose: Current clinical Extra Corporeal CO2 removal systems rely on human intervention to adjust to changes in patient activity. Previous studies have investigated the use of capnography for measurement of arterial blood carbon dioxide tension (PaCO2) using artificial lungs (AL). The presented work demonstrates an initial implementation of a controller that directly monitors and regulates PaCO2 using exhaust gas CO2 (EGCO2) measurements. Method: The system operates through two cycles, namely measurement and control. First, the sweep gas flow through the AL is temporarily (~60s) reduced to ~400 mL/min to allow the CO2 concentration on the blood and gas phase of the AL to equilibrate. This allows for EGCO2 (measured via a CO2Meter GC-0017) values to be used as an estimate of PaCO2. The control cycle is based on Proportional-Integral-Derivative (PID) principle wherein the system automatically modulates sweep gas flows through the AL to minimize the difference between the desired PaCO2 and the estimated PaCO2 (i.e., measured EGCO2). Blood samples were intermittently collected at the inlet of the AL to monitor actual PaCO2 (measured via a Radiometer ABL800 Flex blood gas analyzer). The in vitro study setup (Fig. 1) consists of a Novalung iLA oxygenator (main AL) and a Capiox RX25 oxygenator (conditioning AL) connected in parallel to model a typical ECMO circuit. The blood reservoir mimics the blood volume (7 L) while the centrifugal pump simulates cardiac output (fixed at ~5 L/min) of a patient. Blood flow through the main AL (AV shunt) was regulated at ~1 L/min using a Hoffman clamp. CO2 concentration in the sweep gas through the conditioning AL was modulated to simulate metabolic activity. The baseline CO2 concentration measured at the outlet of the conditioning AL that projects reservoir PaCO2 level when the main AL is not operational. The baseline blood concentration was varied between 45 and 90 mmHg representing all levels of normocapnia and hypercapnia. Results: Prior to the controller testing, a feasibility study was performed to determine the accuracy of capnography technique in calculating the PaCO2 using the AL. A total of forty-two blood samples were collected at blood flow rates of 0.5, 0.6 and 1.0 L/min. The results show a good correlation between PaCO2 and EGCO2 (r2=0.824, P<0.001). There was a reasonable degree of agreement between the PaCO2 and EGCO2 with accuracy (bias or mean difference between PaCO2 and EGCO2) of 6.04 mmHg with a precision (95% limits of agreement) of ± 9.62 mmHg (Fig. 2). Despite the limitation of the AL in estimating PaCO2 using EGCO2, the PID controller implementation demonstrated that average reservoir CO2 concentration can be maintained at 44.23 ± 8.7 mmHg for a target PaCO2 of 40 mmHg (Fig. 3),against baseline blood reservoir PaCO2 of 60.76 ± 13.81 mmHg.Figure 1. Image showing in vitro test setup. The bovine blood in the test circuit was anticoagulated (ACT > 1200s) with heparin and maintained at 37°C.Figure 2. a) The regression curve generated between PaCO2 samples and measured EGCO2 b) Agreement between PaCO2 samples and measured EGCO2.Figure 3. a) In vitro test results showing changes in all PaCO2 concentrations in the circuit b) Result summary comparing average reservoir PaCO2 level with target PaCO2

The purpose of this study was to elucidate the role of the renal nerves in promoting sodium retention during chronic reductions in cardiac output. In five dogs, the left kidney was denervated and the urinary bladder was surgically divided to allow separate 24-h urine collection from the innervated and denervated kidneys. Additionally, progressive reductions in cardiac output were achieved by employing an externally adjustable occluder around the pulmonary artery and by servo-controlling right atrial pressure (control = 0.9 +/- 0.2 mmHg) at 4.7 +/- 0.1, 7.5 +/- 0.1, and 9.8 +/- 0.2 mmHg for 3 days at each level. At the highest level of right atrial pressure, the 24-h values for mean arterial pressure (control = 97 +/- 3 mmHg) and cardiac output (control = 2,434 +/- 177 ml/min) were reduced approximately 25 and 55%, respectively; glomerular filtration rate fell by approximately 35% and renal plasma flow by approximately 65%. However, despite the sodium retention induced by these hemodynamic changes, there were no significant differences in renal hemodynamics or sodium excretion between the two kidneys during pulmonary artery constriction. In contrast, after release of the pulmonary artery occluder on day 9, sodium excretion increased more (approximately 28% during the initial 24 h) in innervated than in denervated kidneys. These results suggest that the renal nerves are relatively unimportant in promoting sodium retention in this model of low cardiac output but contribute significantly to the short-term elimination of sodium after partial restoration of cardiac output and mean arterial pressure.

Hemocompatibility challenge of membrane oxygenator for artificial lung technology

Case Scenario: Hemodynamic Management of Postoperative Acute Kidney Injury

Vasopressors are gaining renewed interest as treatment adjuncts in hemorrhagic shock. The ideal vasoconstrictor will increase systemic blood pressure without increasing pulmonary vascular resistance (PVR), which hinders pulmonary perfusion and exacerbates hypoxemia. However, the selectivity of pressors for pulmonary versus systemic vasoconstriction during hemorrhage has not been characterized. The purpose of this study was to test the hypothesis that vasopressin (VP) has distinct effects on pulmonary versus systemic hemodynamics, unlike the catecholamine vasopressors norepinephrine (NE) and phenylephrine (PE). Anesthetized and ventilated pigs were assigned to resuscitation with saline only (n = 7) or saline with VP (n = 6), NE (n = 6), or PE (n = 6). Animals were hemorrhaged to a target volume of 30 mL/kg and a mean arterial pressure of 35 mmHg. One hour after the start of hemorrhage, animals were resuscitated with saline up to one shed blood volume, followed by either additional saline or a vasopressor. Hemodynamics and oxygenation were measured hourly for 4 h after the start of hemorrhage. Vasopressin increased systemic vascular resistance (SVR) while sparing the pulmonary vasculature, leading to a 45% decrease in the PVR/SVR ratio compared with treatment with PE. Conversely, NE induced pulmonary hypertension and led to an increased PVR/SVR ratio associated with decreased oxygen saturation. Phenylephrine and crystalloid had no significant effect on the PVR/SVR ratio. Sparing of pulmonary vasoconstriction occurs only with VP, not with administration of crystalloid or catecholamine pressors. The ability of VP to maintain blood oxygenation indicates that VP may prevent hypoxemia in the management of hemorrhagic shock.