Extracorporeal Lung Research Articles

Extracorporeal pulmonary support procedures in intensive care medicine 2014

In recent years a rapid expansion of extracorporeal devices for support of severe lung failure has been witnessed. Systems for veno-venous extracorporeal membrane oxygenation (VV-ECMO) or for extracorporeal carbon dioxide elimination are distinguished depending on the indications. The state of the art of extracorporeal lung support is presented with an overview of the different systems, the indications, efficiency and potential side effects. By means of a selective literature research and based on personal experience, the principles and techniques, efficiency and potential side-effects of the new modalities are described. The VV-ECMO systems may be indicated in severe, refractory and predominantly hypoxemic lung failure (pAO2/FIO2 <80 mmHg). Both life-saving gas exchange and a reduction of ventilator-induced lung injury by means of a more protective ventilation can be achieved. Experienced centers can obtain survival rates of more than 60%. Either pumpless arterio-venous devices, also called interventional lung assist (ILA) or low-flow ECMO devices can be used for extracorporeal carbon dioxide elimination in refractory respiratory acidosis. Severe complications can occur with all modalities of extracorporeal support and have to be rapidly recognized and controlled. It must be pointed out that secure evidence based on prospective randomized studies is currently limited for all modalities. Modern extracorporeal lung support devices allow an effective extracorporeal gas exchange and have become an inherent component of intensive care treatment of critically ill patients. Due to potentially severe complications the use should be restricted to specialized centers with experience in the treatment of severe acute respiratory distress syndrome (ARDS).

0671. Extended extracorporeal lung support in a porcine acute lung injury model. Feasibility and preliminary data

During the last years there has been a renewed interest in using extracorporeal membrane oxygenation (ECMO) to treat severe ARDS. ECMO may correct hypoxemia but may also aid in protecting the lungs [1]. However, there is scarce data about the optimal way to ventilate the lungs during ECMO. Experimental models of acute lung injury with ECMO are usually too short.

Electrolyte shifts across the artificial lung in patients on extracorporeal membrane oxygenation: Interdependence between partial pressure of carbon dioxide and strong ion difference

PurposePartial pressure of carbon dioxide (Pco2), strong ion difference (SID), and total amount of weak acids independently regulate pH. When blood passes through an extracorporeal membrane lung, Pco2 decreases. Furthermore, changes in electrolytes, potentially affecting SID, were reported. We analyzed these phenomena according to Stewart's approach. MethodsCouples of measurements of blood entering (venous) and leaving (arterial) the extracorporeal membrane lung were analyzed in 20 patients. Changes in SID, Pco2, and pH were computed and pH variations in the absence of measured SID variations calculated. ResultsPassing from venous to arterial blood, Pco2 was reduced (46.5 ± 7.7 vs 34.8 ± 7.4 mm Hg, P < .001), and hemoglobin saturation increased (78 ± 8 vs 100% ± 2%, P < .001). Chloride increased, and sodium decreased causing a reduction in SID (38.7 ± 5.0 vs 36.4 ± 5.1 mEq/L, P < .001). Analysis of quartiles of ∆Pco2 revealed progressive increases in chloride (P < .001), reductions in sodium (P < .001), and decreases in SID (P < .001), at constant hemoglobin saturation variation (P = .12). Actual pH variation was lower than pH variations in the absence of measured SID variations (0.09 ± 0.03 vs 0.12 ± 0.04, P < .001). ConclusionsWhen Pco2 is reduced and oxygen added, several changes in electrolytes occur. These changes cause a Pco2-dependent SID reduction that, by acidifying plasma, limits pH correction caused by carbon dioxide removal. In this particular setting, Pco2 and SID are interdependent.

Disorders of haemostasis in patients with acute necrotising pancreatitis

Our objective was to investigate the capacity of a pumpless extracorporeal lung membrane (iLA) (Novalung; Novalung GmbH, Hechingen, Germany) to provide adequate respiratory support and the impact on morbidity/mortality during complex airway reconstruction.Only patients unable to be ventilated via conventional intubation were eligible for the study. A larynx mask or orotracheal tubes were placed above the airway defect and the iLA was attached via femoral vessels (arteriovenous), providing extracorporeal gas exchange, apneic hyperoxygenation, and total tubeless airway reconstruction. Haptoglobulin, plasmin–antiplasmin complex, P-selectin activation, and interleukin 6 were measured before, during, and after iLA use and 72 hours postoperatively.Fifteen consecutive patients (age, 42 ± 17 years) underwent elective (n = 7) or emergency (n = 8) reconstruction of the airway owing to a variety of disorders or defects. The iLA was left in place for 185 ± 61 minutes, diverted 1.70 ± 0.48 L/min of the cardiac output, and provided an arteriovenous carbon dioxide removal and oxygen transfer of 173 ± 94 and 144 ± 83 mL/min, respectively. The arterial oxygen tension/inspired oxygen fraction (314 ± 31 mm Hg), and arterial carbon dioxide tension (40 ± 6 mm Hg) remained stable throughout the entire operations. The following procedures were performed: redo slide tracheoplasties (n = 3), redo tracheoesophageal fistula repair (n = 1), sleeve lobectomies (n = 2), main carina reconstructions (n = 7), and anastomotic stenting and myocutaneous coverages (n = 2). Three patients required prolonged (9 ± 2 days) postoperative iLA support. Two (13%) patients died during the hospital stay. The use of iLA was associated with significant (P < .05) but clinically nonrelevant and yet nonpathologic increases of haptoglobulin (hemolysis), plasmin–antiplasmin complex (coagulation activation), and P-selectin activation (platelet activation). Data normalized within 48 hours postoperatively.Data suggest that iLA provides complete intraoperative respiratory support in patients who cannot receive conventional intubation/ventilation without relevant effects on cellular trauma, coagulatory response, and inflammatory response.

Extracorporeal lung support for COPD reaches a crossroad

The natural course of chronic obstructive pulmonary disease usually evolves into a form of acute respiratory failure characterised by alveolar hypoventilation and severe respiratory acidosis. As the severity and frequency of hypercapnic respiratory failure increases, the negative evolution of the syndrome progresses. Non-invasive mechanical ventilation delays fatal evolution through restoration of sufficient alveolar ventilation.1 Unfortunately, such ventilation can fail in up to 40% of the most severe cases and patients then have to undergo invasive ventilation to restore gas exchange.

Effect of flow rate and temperature on transmembrane blood pressure drop in an extracorporeal artificial lung

Transmembrane pressure drop reflects the resistance of an artificial lung system to blood transit. Decreased resistance (low transmembrane pressure drop) enhances blood flow through the oxygenator, thereby, enhancing gas exchange efficiency. This study is part of a previous one where we observed the behaviour and the modulation of blood pressure drop during the passage of blood through artificial lung membranes. Before and after the induction of multi-organ dysfunction, the animals were instrumented and analysed for venous-venous extracorporeal membrane oxygenation, using a pre-defined sequence of blood flows. Blood flow and revolutions per minute (RPM) of the centrifugal pump varied in a linear fashion. At a blood flow of 5.5 L/min, pre- and post-pump blood pressures reached -120 and 450 mmHg, respectively. Transmembrane pressures showed a significant spread, particularly at blood flows above 2 L/min; over the entire range of blood flow rates, there was a positive association of pressure drop with blood flow (0.005 mmHg/mL/minute of blood flow) and a negative association of pressure drop with temperature (-4.828 mmHg/(°Celsius). These associations were similar when blood flows of below and above 2000 mL/minute were examined. During its passage through the extracorporeal system, blood is exposed to pressure variations from -120 to 450 mmHg. At high blood flows (above 2 L/min), the drop in transmembrane pressure becomes unpredictable and highly variable. Over the entire range of blood flows investigated (0-5500 mL/min), the drop in transmembrane pressure was positively associated with blood flow and negatively associated with body temperature.

Influenza A (H1N1) vs non-H1N1 ARDS: Analysis of clinical course

PurposeThe purpose of the study is to compare H1N1-induced acute respiratory distress syndrome (ARDS) with ARDS due to other causes of severe community-acquired pneumonia focusing on pulmonary function. Materials and methodsThis is a retrospective data analysis of adult ARDS patients between January 2009 and December 2010 in an ARDS referral center. Patient characteristics, severity of illness scores, modalities, and duration of extracorporeal lung support were evaluated as well as intensive care unit stay and survival. Parameters of mechanical ventilation and pulmonary function were analyzed on day of admission and over the consecutive 10 days using a nonparametric analysis of longitudinal data in a 2-factorial design. In a logistic regression analysis, risk factors for extracorporeal lung support were investigated. ResultsTwenty-one patients with H1N1-ARDS and 41 with non-H1N1-ARDS were identified. Gas exchange was more severely impaired in patients with H1N1-ARDS over course of time. Extracorporeal membrane oxygenation was more frequently needed in H1N1-ARDS. Despite significantly prolonged weaning off extracorporeal lung support and intensive care unit stay in H1N1 patients, the proportion of survivors did not differ significantly. Only Sepsis-Related Organ Failure Assessment score could be identified as an independent predictor of extracorporeal lung support. ConclusionsClinical course of H1N1-ARDS is substantially different from non-H1N1-ARDS. Affected patients may require extensive therapy including extracorporeal lung support in ARDS referral centers.

Smart ECLA—closed loop control of O2 and CO2 for management of extracorporeal lung assist

tated trace demonstrates high levels of correlation with each of the algorithms in the system. The relative change detection algorithms for heart rate and blood oxygen saturation correlate 97.8% (total events 229) and 98.3% (total events 119) of the time, respectively. The breath pause and apnea detection algorithms correlated 98.9% (total events 2943) and 96.8% (total events 33) of the time, respectively. Conclusions: This study has demonstrated that physiological rulebased computational algorithms can be used to detect the various forms of spells in humanphysiological data. There is great potential for the list of potential causes to be reduced with further research using this tool to demonstrate associations between various spell profiles and different conditions. We have begun clinical validation of the algorithms in a prospective simultaneous comparison trial against the gold standard of polysomnography. Data from 50 spontaneously breathing preterm infants that are known to be having spells will be used to test and refine the output of the algorithms. This trial will form the basis for further studies on ventilated infants with the long-term goal of developing an advanced clinical decision support tool to assist in the real-time management of all neonatal spells.

Pumpless extracorporeal CO2removal restores normocapnia and is associated with less regional perfusion in experimental acute lung injury

Lung protective ventilation may lead to hypoventilation with subsequent hypercapnic acidosis (HA). If HA cannot be tolerated or occurs despite increasing respiratory rate or buffering, extracorporeal CO2-removal using a percutaneous extracorporeal lung assist (pECLA) is an option. We hypothesised that compensation of HA using pECLA impairs regional perfusion. To test this hypothesis we determined organ blood flows in a lung-injury model with combined hypercapnic and metabolic acidosis. After induction of lung injury using hydrochloric acid (HCl) aspiration and metabolic acidosis by intravenous HCl infusion in nine pigs, an arterial-venous pECLA device was inserted. In randomised order, four treatments were tested: pECLA shunt (1) with and (2) without HA, and clamped pECLA shunt (3) with and (4) without HA. Regional blood flows were measured with the coloured microsphere technique. HA resulted in higher perfusion in adrenal glands, spleen and parts of splanchnic area (P < 0.05) compared with normocapnia. During CO2-removal with pECLA, regional perfusion decreased to levels comparable with those without pECLA and normocapnia. Cardiac output (CO) increased during HA without a pECLA shunt and was highest during HA with a pECLA shunt compared with normocapnia. During CO2-removal with pECLA, this variable decreased but stayed higher than during normocapnia with clamped pECLA shunt (P < 0.05). In our lung-injury model, HA was associated with increased systemic and regional blood flow in several organs. pECLA provides effective CO2 removal, requiring a higher CO for perfusion of the pECLA device without improvement of regional organ perfusion.

Disruptive technology in the treatment of thoracic trauma

The care of patients with thoracic injuries has undergone monumental change over the past 25 years. Advances in technology have driven improvements in care, with obvious benefits to patients. In many instances, new or “disruptive” technologies have unexpectedly displaced previously established standards for the diagnosis and treatment of these potentially devastating injuries. Examples of disruptive technology include the use of ultrasound technology for the diagnosis of cardiac tamponade and pneumothorax; thoracoscopic techniques instead of thoracotomy, pulmonary tractotomy, and stapled lung resection; endovascular repair of thoracic aortic injury; operative fixation of flail chest; and the enhanced availability of extracorporeal lung support for severe respiratory failure. Surgeons must be prepared to recognize the benefits, and limits, of novel technologies and incorporate these methods into day-to-day treatment protocols.

An Original Versatile Nonocclusive Pressure‐Regulated Blood Roller Pump for Extracorporeal Perfusion

Currently, only a small number of centrifugal pumps are being used for hemodynamic and/or respiratory support, but all of them have limitations. This article aims to present the Rhône-Poulenc 06 nonocclusive pressure-regulated blood pump. This pump was developed in France in the 1970s and used for decades in perfusion for cardiopulmonary bypass procedures, cardiac or lung assist as well as venovenous bypass during liver transplant. The intrinsic properties of this pump allowed us to describe a new technique for extracorporeal lung support in the 1980s, using a single cannula tidal flow venovenous bypass. This pump compared favorably with conventional pumps in terms of flow and pressure, hemolysis, pulsatility, safety, and cost-effectiveness. We believe that this simple pump could be an alternative to more sophisticated and expensive devices.

Extracorporeal Lung Support in H1N1 Provoked Acute Respiratory Failure

During the H1N1 pandemic of 2009 and 2010, the large number of patients with severe respiratory failure due to H1N1 infection strained the capacities of treatment facilities for extracorporeal membrane oxygenation (ECMO) around the world. No data on this topic have yet been published for Germany. During the pandemic, the German ARDS Network (a task force of the DIVI's respiratory failure section) kept track of the availability of ECMO treatment facilities with a day-to-day, Internet-based capacity assessment. In cooperation with the Robert Koch Institute, epidemiological and clinical data were obtained on all patients treated for influenza in intensive care units. 116 patients were identified who had H1N1 disease and were treated in the intensive care units of 9 university hospitals and 3 other maximum medical care hospitals. 61 of them received ECMO. The overall mortality was 38% (44 of 116 patients); among patients receiving ECMO, the mortality was 54% (33 of 61 patients). The mortality was higher among patients who had an accompanying malignancy or immune deficiency (72.2%). Even persons without any other accompanying disease developed life-threatening respiratory failure as a result of H1N1 infection, and many of these patients needed ECMO. This study reveals for the first time that the mortality of H1N1 infection in Germany is comparable to that in other countries. H1N1 patients with acute respiratory failure had a worse outcome if they also had serious accompanying diseases.

Use of pumpless extracorporeal lung assist as rescue therapy in adolescent with cystic fibrosis

There is abundant evidence that artificial ventilation can aggravate pre-existing lung disease, which may contribute to morbidity and mortality. This is especially true for patients with air leakages. This case report describes the use of a pumpless extracorporeal lung assist as a rescue therapy to provide time to heal during the mechanical ventilation of a 16-year-old with cystic fibrosis who could not be managed via conventional means.

Safety of percutaneous dilatational tracheostomy in patients on extracorporeal lung support

To evaluate the safety of percutaneous dilatational tracheostomy (PDT) in critically ill patients on an extracorporeal lung assist device requiring therapeutic anticoagulation. This was a retrospective, observational study on all patients undergoing tracheostomy while on pumpless extracorporeal lung assist or extracorporeal membrane oxygenation in intensive care units of two university hospitals in Germany between 2007 and 2013. During the study period PDT was performed on 118 patients. The median platelet count, international normalized ratio, and activated partial thromboplastin time before tracheostomy were 126 × 10(9)/L (range 16-617 × 10(9)/L), 1.1 (0.9-2.0) and 49 s (28-117 s), respectively. Seventeen patients (14.4%) received a maximum of three bags of pooled platelets, and eight patients (6.8%) received a maximum of four units of fresh frozen plasma before the procedure. In all patients the administration of intravenous heparin was briefly paused periprocedurally. No periprocedural clotting complication within the extracorporeal circuit was observed. Two patients (1.7%) suffered from procedure-related major bleeding, with one patient requiring conversion to a surgical tracheostomy. Two pneumothoraces (1.7%) were related to the PDT. One patient (0.8%) had analgosedation-related hypotension with brief and successful cardiopulmonary resuscitation. Minor bleeding from the tracheostomy site occurred in 37 cases (31.4%). No fatality was attributable to tracheostomy. The complication rates of PDT in the patients on extracorporeal lung support were low and comparable to those of other critically ill patients. Based on these results, we conclude that PDT performed by experienced operators with careful optimization of the coagulation state is a relatively safe procedure and not contraindicated for this patient group.

Quality Assurance Would Be Welcome

We congratulate our colleagues on their comprehensive review article on using extracorporeal lung support devices in patients with acute pulmonary distress syndrome (ARDS) (1). Technical improvements and the challenges in the context of the H1N1 influenza pandemic have undoubtedly led to a renaissance of extracorporeal membrane oxygenation (ECMO). The promising trend towards a reduced mortality associated with increasing experience in using the technique, as described by the authors, is indisputable and supports a recent publication from the United Kingdom’s ECMO-centers (2). Nevertheless this confirms primarily the positive correlation between dedicated center-based experience in treating severe ARDS and outcome, also mentioned in different expert discussions. For this reason, the encouraging data from Regensburg and other specialized ECMO-centers should not prompt the uncritical popularization and use of extracorporeal lung support. In spite of miniaturised techniques and a simpler handling, ECMO remains a technically and pathophysiologically highly complex treatment modality that has to be supported by multimodal therapeutic management and expertise of different medical specialties. The challenges inherent to the procedure, as well as the possible life-threatening complications, can only be met in centers that ensure comprehensive logistical and structural conditions at any time of day or night, as the authors rightly comment. On this background and from the perspective of the authors – and in analogy to the treatment of other diseases – quality assurance measures for the treatment of severe ARDS by using extracorporeal lung support would be extremely welcome (3).

The Effect of Pumpless Extracorporeal CO2 Removal on Regional Perfusion of the Brain in Experimental Acute Lung Injury

Lung-protective mechanical ventilation with low tidal volumes (V(T)) is often associated with hypercapnia (HC), which may be unacceptable in patients with brain injury. CO2 removal using a percutaneous extracorporeal lung assist (pECLA) enables normocapnia despite low V(T), but its effects on regional cerebral blood flow (rCBF) remain ambiguous. We hypothesized that reversal of HC by pECLA impairs rCBF in a porcine lung injury model. Lung injury was induced in 9 anesthetized pigs by hydrochloric acid aspiration. rCBF and systemic hemodynamics were measured by colored microsphere technique and transpulmonary-thermodilution during a randomized sequence of 4 experimental situations: pECLA shunt-on (1) with HC and (2) without HC, pECLA shunt-off (3) with HC and (4) without HC. HC increased rCBF (P<0.05). CO2 removal with pECLA resulting in normocapnia, decreased rCBF to levels comparable to those without pECLA and normocapnia. HC resulted in increased cardiac output (+25.5%). Cardiac output was highest during HC with pECLA shunt (+44.9%). During pECLA with CO2 removal, cardiac output (+38.1%) decreased compared with pECLA without CO2 removal, but stayed higher than during normocapnia/no pECLA shunt (P<0.05). In this animal model, mechanical ventilation with low V(T) was associated with HC and increased rCBF. CO2 removal by pECLA restored normocapnia, reduced rCBF to levels of normocapnia, but required a higher systemic blood flow for the perfusion of the pECLA device. If these results could be transferred to patients, extracorporeal CO2 removal might be an option for treatment of combined lung and brain injury in condition of a sufficient cardiac flow reserve.

Clinical Research During a Public Health Emergency

Rigorous evaluation of clinical interventions in the setting of a public health emergency is necessary to identify best practices, to develop clinical management guidelines, and to inform resource allocation. The 2009 influenza A (H1N1) pandemic necessitated care of critically ill patients around the world. To inform the World Health Organization Public Health Research Agenda for Influenza, we conducted a systematic review to identify clinical interventions other than antiviral therapies that would benefit severely ill 2009 H1N1 influenza patients (adults and children) in both high- and low-resource settings. PubMed, EMBASE, Cochrane Central Register of Clinical Trials, and Cochrane Database of Systematic Reviews; hand search of abstracts from six professional society annual conferences and bibliographies of clinical review articles; and personal communication with leaders in the field. English language; human studies; citations added to databases from January 1, 2009 (Cochrane databases) or March 15, 2009 (PubMed and EMBASE) through January 31, 2012; randomized controlled trials, prospective cohort studies, or systematic reviews/meta-analyses of non-antiviral clinical interventions in hospitalized 2009 influenza A (H1N1) patients. The search identified 2,452 articles. Thirty-six potentially relevant articles were read. Seven articles met criteria. All were observational studies. One study found benefit of convalescent plasma infusion, three studies found no benefit of corticosteroids, and three studies had mixed results on the benefit of extracorporeal lung support. No study was applicable to health care delivery in low-resource settings. There is a paucity of high quality clinical research to inform clinical care of severe H1N1 influenza, and we found no beneficial interventions appropriate for low-resource settings. This may be due to the logistical difficulties of conducting clinical research in response to a public health emergency. Our investigation underscores the need for the development of outbreak-ready research capacity in both high- and low-resource settings.

Combined use of pumpless extracorporeal lung assist system and continuous renal replacement therapy with citrate anticoagulation in polytrauma patients

The usefulness of a pumpless extracorporeal lung assist system (pECLA) and continuous renal replacement therapy (CRRT) in critically ill patients has been demonstrated in previous studies [1,2]. The aim of this report was to examine combined use of pECLA and CRRT to improve carbon dioxide and inflammatory mediator removal, which allows for lung protective ventilation strategies.

Transportable extracorporeal lung support for rescue of severe respiratory failure in combat casualties

Transportable extracorporeal lung support for rescue of severe respiratory failure in combat casualties

Tumor Necrosis Factor-α Plays an Initiating Role in Extracorporeal Circulation-induced Acute Lung Injury

Despite advances in critical care, the mortality rate for patients with acute lung injury (ALI) remains high. The aim of this study was to test the hypothesis that tumor necrosis factor-α (TNF-α) plays an initiating role in the onset of extracorporeal circulation (ECC)-induced ALI. Eight New Zealand rabbits subjected to 1h of ECC and 40min of observation after termination of ECC were used for monitoring pulmonary nociceptor activity. Fifty Sprague-Dawley (SD) rats that received 2h of ECC and 4h of rest were used to measure the pulmonary function and inflammatory cytokines release, including total cells, neutrophils, and TNF-α in bronchoalveolar lavage (BAL) and white blood cell (WBC) and neutrophils in blood. An additional 40 SD rats were randomized to pretreatment with inhalation of phosphate buffer solution (control group), IgG (IgG inh group), or TNF-α antibody (anti-TNF-α inh group) and venous injection of TNF-α antibody (anti-TNF-α iv group). After 2h of ECC and 4h of rest, the arterial blood and BAL fluid were collected for measurement of arterial oxygen pressure (PaO2) and inflammatory cytokines release. The left-lower-lung tissues of animals were stained with hematoxylin & eosin (H&E). The results demonstrated that the activities of airway nociceptor and TNF-α release were similarly upregulated at the early stage and in a time-related manner in ECC-induced ALI. Pretreatment with TNF-α antibody inhalation, but not venous injection, improved pulmonary function, inhibited pulmonary inflammation, and attenuated pulmonary histopathological changes after ECC. We concluded that TNF-α played an important role in the pathogenesis of ALI and acted as an initiating cytokine at the early stage of ECC-induced ALI.