The evolving role and practical application of extracorporeal carbon dioxide removal in critical care

Transcription

1 The evolving role and practical application of extracorporeal carbon dioxide removal in critical care Nicholas A Barrett and Luigi Camporota Extracorporeal carbon dioxide removal ( ) has become increasingly popular in critical care over the last 5 10 years for the management of hypercapnic respiratory failure or to facilitate ultra-protective ventilation in patients with acute respiratory distress syndrome (ADS). 1 provides partial respiratory support by clearing 25% 30% of produced CO 2 from the venous blood with minimal direct impact on systemic oxygenation using blood flows of 0.5 L/ min. 2-4 By reducing the CO 2 needing to be cleared by the native lungs, allows for a lower native pulmonary alveolar minute ventilation, an improvement in lung mechanics, and a reduction in the resistive and elastic work of breathing. 1 may be used either as an adjunct or as an alternative to conventional intensive care unit supportive therapy in a range of conditions with persisting hypercapnia. It is important to appreciate the impact of on: 1) work of breathing; 2) maximal CO 2 removed; 3) interactions with the native lung; 4) control of the respiratory drive in awake patients; 5) potential complications of, particularly bleeding and thrombosis; 6) modifications in management that are necessary once the patient is established on. This review will focus on exploring how the devices clear CO 2, the impact of on the native pulmonary physiology and systemic gas exchange, and modifications to patient management required while on. Gas exchange across the membrane membranes enable gas exchange in a manner analogous to the native lung. 5 Modern hollow-fibre membranes are constructed of polymethylpentene (PMP) or siloxane. 6 There is a capillary network within the membrane allowing a flow of gas and blood through separate channels and gases to move down their concentration gradient. 7 CO 2 production (VCO 2 ) is directly related to oxygen (O 2 ) consumption (VO 2 ), through a proportionality constant called the respiratory quotient (VCO 2 /VO 2 ), which, although usually assumed equal to 0.8, becomes variable in patients on extracorporeal support, depending on the efficiency of the membrane, the gas flow and the venous PaCO 2. The greater the CO 2 removed by the device, the lower the respiratory quotient ABSTACT Objective: Extracorporeal venovenous carbon dioxide removal ( ) is increasingly used to facilitate ultraprotective mechanical ventilation, or to prevent or avoid mechanical ventilation in selected patients. This review focuses on how extracorporeal devices clear CO 2, their impact on native pulmonary physiology, and systemic gas exchange. Finally, we discuss the modifications to patient management required while on. Crit Care esusc 2017; 19 (Suppl 1): The VCO 2 of an adult at rest is about 3 ml/kg/min. CO 2 is carried in the blood in solution (5%), as carbonic acid (85%), or bound to proteins (10%) including haemoglobin. Because of its higher solubility compared with O 2, CO 2 diffuses about 20 times faster than O Consequently, the removal of CO 2 can occur at relatively lower extracorporeal blood flows (0.5 1 L/min) than does the transfer of clinically relevant amounts of O 2 (4 5 L/min). In a perfectly efficient system, a blood flow of 0.5 L/min would be sufficient to remove all the CO 2 produced However, CO 2 clearance depends on the gradient between the CO 2 in the venous blood, the sweep gas CO 2, sweep gas flow rate, blood CO 2 content, ph and haemoglobin, 19 as well as the efficiency of the gas exchange membrane. Blocked capillary channels in the extracorporeal lung can result in intra-membrane dead space and shunt, reducing its efficiency. These factors limit the amount of CO 2 removed from the blood and is usually able to remove up to 25% of carbon dioxide production. 20,21 Blood flow through the artificial lung is analogous to the perfusion of the native lung, while the sweep gas flow rate is analogous to minute ventilation. Increasing sweep gas flow rate increases CO 2 clearance 22 until a maximum blood flow/sweep gas flow ratio is reached, beyond which CO 2 removal does not increase. In clinical practice, a ventilation/ perfusion ratio of 10 11:1 (5 6 L/min of gas flow for 0.5 L/ min blood flow) is the point of maximal CO 2 removal. 22 The relationship between CO 2 clearance and blood flow is non-linear; at low sweep flow rates, CO 2 clearance is highly sensitive to changing sweep flow rates; but at high sweep flow rates the CO 2 clearance is relatively insensitive. 22,23 62 Critical Care and esuscitation Volume 19 Supplement 1 October 2017

2 CO 2 also exhibits biphasic kinetics, with an initial rapid decline in PaCO 2 followed by a slower decline. This is caused by the rapid removal of dissolved CO 2 followed by equilibration of carbonic acid, carboxyhaemoglobin and tissue stores of CO Although, from a physiological point of view calculating the amount of CO 2 removed from the blood is essential to understanding the interaction between the artificial and the native lung, from a clinical viewpoint, the exact amount of CO 2 exchanged by the membrane is generally not measured. ather, the sweep gas flow rate is merely changed to maintain an appropriate systemic arterial PCO 2 and work of breathing. Should CO 2 control deteriorate, although patient factors are the most likely cause, it is important to remember that microthrombi in the membrane or water accumulation on the gas side of the membrane will reduce the capacity for CO 2 diffusion. 25 It is also important to appreciate that often the goal of is not necessarily the reduction in PaCO 2, but the control of PaCO 2 to allow a reduction in the mechanical ventilation or a reduction in work of breathing. Impact of on native lung physiology The impact of on native lung physiology is poorly understood. The most consistent effect of in both clinical and pre-clinical studies is to reduce mixed venous PCO 2 and to improve arterial ph Associated with this reduction is a simultaneous reduction in respiratory rate and hence minute ventilation. 26,29,32 The ultimate effect on arterial PCO 2 depends on multiple factors related to the underlying pathological process. For patients with exacerbation of chronic obstructive pulmonary disease (COPD), the reduction in respiratory rate and tidal volume that results from the reduction in the venous PCO 2 increases expiratory time, allowing a reduction in intrinsic positive end-expiratory pressure (PEEP) and end-inspiratory lung volume, improving alveolar dead space and alleviating any flattening of the diaphragm, which decreases respiratory work. 33 There are limited data available about the impact of on other aspects of pulmonary physiology in clinical settings. A small pilot study reported on the changes associated with in patients with COPD weaning from a ventilator and found that intrinsic PEEP, inspiratory pulmonary resistance and work of breathing were all reduced. 34 The intended benefits of as an adjunct to ADS are to allow a reduction in tidal volumes and respiratory rate, as well as plateau and, possibly, mean airway pressures. 29,35-38 However, in moderate or severe ADS, may have important detrimental effects on oxygenation. A reduction in tidal volumes without a significant increase in PEEP decreases the mean airway pressure (mpaw) and therefore the mean lung volume. A reduction in mpaw may lead to derecruitment, progressive atelectasis and hypoxaemia. 8,37 The effect on the PaO 2 /FiO 2 ratio has been variably reported in the literature, 34,37 likely due to clinicians altering ventilator settings, particularly PEEP. 26,29,37 Arterial hypoxaemia may be further aggravated by a reduction in hypoxic pulmonary vasoconstriction due to the improvement in mixed venous PO 2 caused by the return of oxygenated blood into the great veins, which leads to an increased native lung shunt fraction. The effect on the abolition of hypoxic vasoconstriction will depend on the venous PO 2 and the cardiac output but also the underlying lung disease. In patients with severe lung inflammation, hypoxic vasoconstriction may already be abolished and a change in mixed venous PO 2 will have little additional effect, while in patients with preserved hypoxic vasoconstriction, may lead to severe hypoxaemia. 21,39-41 also causes important changes in the partial pressure of alveolar gases, leading to a reduction of alveolar PO 2 (PAO 2 ) and alveolar nitrogen. Alveolar nitrogen reduces because the gradient between the nitrogen in the alveoli and the nitrogen in the blood returned from the artificial lung favours its diffusion out of the alveoli, with consequent reabsorption atelectasis. The reduction in PAO 2 is due to a reduction in mixed venous PaCO 2 and the increase in the respiratory quotient. This leads, according to the alveolar gas equation, to a reduction in the PAO 2 if FiO 2 is kept constant. 39 The resultant effect could lead to a worsening of shunt fraction. There are data to support an improvement in right ventricular function associated with the use of. The effect of hypercapnia on the right ventricle has been well described. Hypercapnia, hypoxaemia, acidosis, pulmonary shunt and hypoxic pulmonary vasoconstriction all contribute to pulmonary arterial hypertension leading to increased right ventricular afterload. 42,43 This is further compounded by the effects of high mean intrathoracic pressures secondary to positive pressure ventilation. ight ventricular contractility is reduced by the effects of hypoxaemia and acidosis on cardiac myocytes, as well as the relative ischaemia caused by increased right ventricular end diastolic pressure due to acute pulmonary hypertension. The net effect of these insults is that the right ventricle dilates and fails. 42 As it does so, the left ventricular function reduces due to ventricular interdependence, and organs including the liver are exposed to a lower cardiac output with higher venous pressure and lower arterial pressure, resulting in organ oedema, dysfunction and ultimately failure. The clearance of CO 2 and resolution of respiratory acidosis result in reduced pulmonary arterial pressure and improved cardiac myocyte contractility, with consequent improvement in indices of right ventricular function. 44,45 This is manifested Critical Care and esuscitation Volume 19 Supplement 1 October

3 by normalisation of right ventricular cross-sectional area, improvement in right ventricular end diastolic pressure, and improvement in radial and longitudinal contractility. The improvement in right ventricular function is also associated with an overall improvement in cardiac output and left ventricular function. 44,45 Current roles for Large randomised controlled trials have not yet been undertaken exploring the role of. Observational studies and case reports have described its use in hypercapnic respiratory failure, particularly for exacerbations of COPD and as an adjunct to allow lung protective ventilation. For ADS, the key intervention in the ICU has been the application of lung-protective ventilation. Strategies which facilitate lung protection and have been shown to improve mortality include optimal PEEP levels; 46 mechanical ventilation with plateau pressure < 30 cmh 2 O and tidal volumes normalised to predicted body weight; 47,48 ventilation in the prone position; and cisatracurium infusion Those providing improved oxygenation alone (eg, inhaled nitric oxide) have not been shown to improve mortality. Patients with severe ADS (PaO 2 /FiO 2 < 13.3 kpa) 52 or significant hypercapnia (ph < 7.20 due to respiratory acidosis) have a significantly higher mortality. 46,53 has been postulated to have two potential roles in ADS. The first is control of hypercapnia using conventional lungprotective ventilation. The second is to facilitate ultraprotective ventilation (tidal volume < 4 ml/kg predicted body weight). The rationale behind the latter approach is that patients with severe ADS have a smaller available lung volume, and that ventilation with tidal volumes of 6 ml/ kg predicted body weight results in excessive lung strain. 54 The addition of to facilitate this ultraprotective approach has been shown to be feasible, although without demonstrable mortality benefit. Acute exacerbations of COPD commonly require noninvasive ventilation (NIV) 3 but 25% 50% of patients with COPD fail to improve and require invasive mechanical ventilation. 55,56 These patients often have a prolonged hospital stay and an in-hospital mortality of 25% 39%. 4 8,28 Given this, is being considered as an adjunctive therapy to NIV to facilitate the withdrawal of NIV, avoid intubation or facilitate early extubation ,57,58 A retrospective cohort study showed lower intubation rates and mortality than propensity-matched historical controls. 32 Patients awaiting lung transplantation who develop lifethreatening hypercapnia may also benefit from as bridge to lung transplantation. 59 Modifications to respiratory management Technical aspects There are some significant modifications to patient management associated with. Cannulation has been associated with significant complications, 31,36 although these may be reduced using venovenous rather than arteriovenous cannulation. 29 The success and safety may also be improved by a structured approach using periprocedural antibiotics, ultrasound, stiffer guidewires, tapered dilators and specific training. 60 Bleeding complications associated with are also common. 26,61 Bleeding is partly due to the requirement for anticoagulation therapy, and partly due to the effects of centrifugal pumps and nonbiological surfaces on the coagulation system, including acquired von Willebrand s factor deficiency, reduction in platelet count and function and a reduction in coagulation factors Unfortunately, bleeding and thrombosis co-exist with extracorporeal support both within the circuit and the patient, particularly with respect to deep vein thrombosis. 65 Other conditions, including haemolysis related to the circuit and centrifugal pump, also occur. 66 ADS Given the changes in native pulmonary physiology associated with in ADS, particularly the development of worsening atelectasis leading to hypoxaemia, PEEP needs to be re-titrated, potentially via a recruitment manoeuvre to maintain systemic oxygenation. 37 Given that one of the goals of is to reduce plateau pressures and tidal volumes, the net effect is to maintain mean airway pressure through an increase in PEEP and a reduction in driving pressure (the difference between plateau and PEEP). COPD As the work of breathing reduces with, the key clinical goals are to facilitate either early extubation 31,38,67 or to prevent intubation. may also be used facilitate the removal of non-invasive ventilation, 29 particularly in patients who tolerate NIV poorly. 58 It is important to remember that the clinical progress will depend on the triggering aetiology and the may be required for days to weeks. 29,32 Thought should be given to the early institution of oral diet and mobilisation. Conclusions is becoming a feasible means to facilitate ultraprotective mechanical ventilation or potentially avoid mechanical ventilation in select patient groups. While there is a clear theoretical rationale for in COPD and purely hypercapnic respiratory failure, and to reduce the 64 Critical Care and esuscitation Volume 19 Supplement 1 October 2017

4 mechanical power in ADS, patient selection is crucial to the success of the technique. Consideration of the interaction between the mechanical and the natural lung, as well as the results of EST and SUPENOVA will affect patient selection and clinical application of in hypoxaemic respiratory failure. Finally, this article must be seen in the context of a dedicated issue that explores multiple aspects of extracorporeal life support in the critically ill Competing interests None declared. Author details Nicholas A Barrett Luigi Camporota Department of Adult Critical Care, St Thomas Hospital, Guy s and St Thomas NHS Foundation Trust, King s Health Partners, London, United Kingdom. Correspondence: nicholas.barrett@gstt.nhs.uk eferences 1 Camporota L, Barrett N. Current applications for the use of extracorporeal carbon dioxide removal in critically ill patients. Biomed es Int 2016; 2016: Hilty MP, iva T, Cottini S, et al. 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6 61 Kalbhenn J, Neuffer N, Zieger B, Schmutz A. Is extracorporeal CO2-removal really safe and less invasive? Observation of blood injury and coagulation impairment during ECCO2. ASAIO J 2017; Feb 7. doi: /MAT [Epub ahead of print] 62 eynolds MM, Annich GM. The artificial endothelium. Organogenesis 2011; 7: Panigada M, Iapichino GE. Dealing with complications of extracorporeal life support. Minerva Anestesiol 2016; 82: Panigada M, Artoni A, Passamonti SM, et al. Hemostasis changes during veno-venous extracorporeal membrane oxygenation for respiratory support in adults. Minerva Anestesiol 2016; 82: Cooper E, Burns J, etter A, et al. Prevalence of venous thrombosis following venovenous extracorporeal membrane oxygenation in patients with severe respiratory failure. Crit Care Med 2015; 43: e Malfertheiner MV, Philipp A, Lubnow M, et al. Hemostatic changes during extracorporeal membrane oxygenation: a prospective randomized clinical trial comparing three different extracorporeal membrane oxygenation systems. Crit Care Med 2016; 44: Braune S, Sieweke A, Brettner F, et al. The feasibility and safety of extracorporeal carbon dioxide removal to avoid intubation in patients with COPD unresponsive to noninvasive ventilation for acute hypercapnic respiratory failure (ECLAI study): multicentre case-control study. Intensive Care Med 2016; 42: Austin DE, Kerr SJ, Al-Soufi S, et al. Nosocomial infections acquired by patients treated with extracorporeal membrane oxygenation. Crit Care esusc 2017; 19 (Suppl1): affa GM, Gelsomino S, Sluijpers N, et al. In-hospital outcome of post-cardiotomy extracorporeal life support in adult patients: the Maastricht experience. Crit Care esusc 2017; 19 (Suppl1): Malfertheiner MV, Broman LM, Belliato M, et al. Management strategies in venovenous extracorporeal membrane oxygenation: a retrospective comparison from five European centres. Crit Care esusc 2017; 19 (Suppl1): Sinnah F, Shekar K, Abdul-Aziz MH, et al. Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation. Crit Care esusc 2017; 19 (Suppl1): Critical Care and esuscitation Volume 19 Supplement 1 October