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Inhaled Sedation in Patients With Acute Respiratory Distress Syndrome Undergoing Extracorporeal Membrane Oxygenation

Meiser, Andreas, MD*; Bomberg, Hagen, MD*; Lepper, Philipp M., MD; Trudzinski, Franziska C., MD; Volk, Thomas, MD*; Groesdonk, Heinrich V., MD*

doi: 10.1213/ANE.0000000000001915
Critical Care and Resuscitation: Brief Report
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Six patients suffering from acute respiratory distress syndrome with the need for extracorporeal membrane oxygenation (ECMO) therapy in deep sedation were included. Isoflurane sedation with the AnaConDa system was initiated within 24 hours after initiation of ECMO therapy and resulted in a satisfactory sedation (Richmond Agitation-Sedation Scale −4 to −5). Despite deep sedation, spontaneous breathing was possible in 6 of 6 patients. We observed a reduced need for vasopressor therapy and improved lung function (PaO2, PaCO2, delta P, and tidal volume) during isoflurane sedation. Opioid consumption could be reduced, and only very low doses of isoflurane were needed (1–3 mL/h). This small case series supports the feasibility of sedation using inhaled anesthetics concurrently with venovenous ECMO.

Published ahead of print March 15, 2017.

From the Departments of *Anesthesiology, Intensive Care Medicine and Pain Medicine, and Internal Medicine V, Saarland University Medical Center, Homburg/Saar, Germany.

Accepted for publication December 16, 2016.

Published ahead of print March 15, 2017.

Funding: None.

Conflicts of Interest: See Disclosures at the end of the article.

Reprints will not be available from the authors.

Address correspondence to Heinrich V. Groesdonk, MD, Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, University Medical Center, University of Saarland, Kirrbergerstrasse 1, 66421 Homburg/Saar, Germany. Address e-mail to heinrich.groesdonk@uks.eu.

Controlled airway pressure therapy, prone positioning, and extracorporeal membrane oxygenation (ECMO) are often required for patients suffering from severe acute respiratory distress syndrome (ARDS).1 Deep sedation is often needed during this treatment, especially when patients are positioned prone. Current German and Spanish sedation guidelines recommend sedation using an inhaled anesthetic such as isoflurane and delivered by the AnaConDa system as an alternative to intravenous (IV) sedation.2,3

Isoflurane also has bronchodilatory effects4,5 and lung-protective properties,6 which may have benefit in patients with ARDS and receiving ECMO therapy.

The AnaConDa system (Sedana Medical, Uppsala, Sweden), commercially available in Europe and Canada, can be used to deliver inhaled anesthetics via common intensive care ventilators. The device is connected between the y piece of the breathing circuit and the endotracheal tube. Liquid isoflurane is continuously infused by a syringe pump into the device where it evaporates on the surface of a porous evaporator rod. Ninety percent of exhaled isoflurane is retained by an anesthetic reflector and resupplied to the patient during the next inspiration.

Use of isoflurane sedation in ARDS patients treated with ECMO is relatively novel and raises several feasibility and safety questions. Given that isoflurane is administered via inhalation, the pharmacokinetics are uncertain when given in ARDS patients with low tidal volumes and poor lung function. In addition, the influence on pulmonary function, hemodynamics, and opioid consumption in ARDS patients requiring ECMO is unknown. Therefore, we report our experience with a consecutive cohort of 6 patients with ARDS, ECMO therapy, and isoflurane sedation.

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CASE DESCRIPTION

This retrospective case analysis was approved by the local ethics committee (Saarland Medical Chamber, Faktoreistr. 4, 66111 Saarbruecken, Germany). We report on 6 patients treated in the surgical intensive care unit (ICU) at the Saarland University Medical Center in Homburg, Germany.

The case series includes all patients receiving isoflurane sedation during ECMO therapy between October 2013 and May 2015. The choice of isoflurane sedation during ECMO therapy was a consensus decision of more than 3 physicians.

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Data Source and Measurements

Simplified acute physiology score II and vital parameters such as heart rate, invasive mean arterial pressure, blood gases, and ventilatory parameters were extracted from the ICU patient data management system (Copra, Version 5, Copra System GmbH, Berlin, Germany). Comorbidities, diagnostic data, drug doses, Richmond Agitation-Sedation Scale (RASS), and ECMO approach were entered manually into this system. The figures were made with GraphPad Prism 5.0 (GraphPad Software, Inc, San Diego, CA). Differences between before isoflurane and after 1 or 24-hour isoflurane were compared by using t tests. Statistical significance was accepted at P ≤ .05.

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Patient Description

Table 1

Table 1

The patients’ medical history before ECMO therapy is shown in Table 1. Causes of the ARDS were pneumonia or sepsis from other sources of infection. The simplified acute physiology score II scores were between 31 and 55 points at the start of ECMO therapy. All patients were treated with prone positioning or kinetic lateral rotation therapy. All patients were mechanically ventilated with pressure-controlled ventilation, and no muscle relaxants were used. Reasons for ECMO therapy were severe oxygenation failure, severe respiratory acidosis, or both (Table 1). Heart failure was excluded in all patients using transesophageal echocardiography.

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ECMO Therapy

Venovenous ECMO therapy was initiated by our team before transfer to ICU (cases 1, 3, 5), immediately after arrival (case 4), or else after 3 (case 6) or 10 days (case 2), respectively. In all cases, the Cardiohelp-System (MAQUET Getinge Group, Rastatt, Germany) with a 7-L heparin-coated oxygenator was used. The sweep gas was 100% oxygen in all cases, and the fraction of inspired oxygen on the ventilator was set to 0.3.

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ISOFLURANE SEDATION

Isoflurane sedation was initiated within 24 hours after initiation of ECMO therapy. The AnaConDa system (Sedana Medical, Uppsala, Sweden) and the Vamos gas monitor (Dräger Medical, Lübeck, Germany) were set up as prescribed by the manufacturer. We used closed endotracheal suctioning in all patients (Optiflo, Dahlhausen Medizintechnik, Köln, Germany). Patients were ventilated with an Evita 4 ventilator (Dräger Medical). Ventilation continued unchanged. The gas outlet of the ventilator was connected to a FlurAbsorb anesthetic gas filter (Sedana Medical). Liquid isoflurane was delivered by a syringe pump (Perfusor; Braun Melsungen AG, Germany). After priming the system, isoflurane was started at a rate of 3 mL/h and adjusted according to the clinical condition (hemodynamic stability, RASS Scores −4 to −5).

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Sedation

With the exception of opioid therapy, previously used IV sedation was stopped before initiating inhaled sedation (Table 1). After initiation of isoflurane sedation, deep sedation (RASS −4 to −5) was readily achievable. The dose of isoflurane was very low with 1 - 3 mL/h with end-tidal concentrations ranging from 0.5 to 0.7 vol%. No technical problems during isoflurane sedation were encountered.

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Lung Function

Table 2

Table 2

Figure

Figure

Interestingly, after 24 hours of isoflurane sedation, all patients were able to breathe spontaneously during deep sedation (Table 2). Also, in all cases, delta P (peak inspiratory pressure − positive end-expiratory pressure) could be reduced, whereas tidal volumes were increased (Figure). We also found that PaO2 and PaCO2 improved on inhaled sedation while ECMO pump flow and ECMO oxygen flow remained constant or decreased (Table 1).

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Hemodynamics

Inhaled sedation was not associated with hemodynamic instability. The norepinephrine dose was reduced with use of inhaled sedation in 5 cases and increased in the sixth. (Figure). The mean arterial pressure decreased in 1 case but remained above 60 mm Hg. In the 2 cases with tachycardia, heart rate decreased after 24 hours, and in the other cases, it remained constant. After 24 hours of isoflurane sedation, opioid consumption was decreased in all cases (Figure).

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DISCUSSION

In this case series, we describe the successful use of isoflurane sedation with the AnaConDa system in 6 patients being treated with ECMO for respiratory failure. We found this strategy feasible, with theoretical advantages including bronchodilation,4,5 cardio-7 and lung-protective effects,8,9 good control of the level of sedation,10,11 and the ability to achieve deep sedation. Some data also suggest that the mortality of long-term ventilated critically ill patients sedated with isoflurane may be lower than that of patients sedated intravenously with propofol or midazolam.12

In some of our patients, tidal volume was below 100 mL initially, but increased to above 180 mL during inhaled sedation. With a small tidal volume, isoflurane that is injected into the AnaConDa device between the reflector and the patient may not be delivered to the gas-exchanging areas of the lung with the first inspiration. We did not find any difficulties in administering isoflurane in doses sufficient to produce deep sedation. Wash-in was quick enough to keep patients sedated after IV sedatives were stopped abruptly.

Severe respiratory acidosis may be 1 reason to install ECMO therapy. Because of the 100-mL internal dead space and CO2 reflection, carbon dioxide removal is impaired with the AnaConDa device.11,13,14 Consequently, tidal volumes above 350 mL are normally recommended, which may preclude use of this device when low-volume lung-protective ventilation strategies are used. However, device dead space is less concerning during ECMO therapy where carbon dioxide may be eliminated via both the oxygenator membrane and tidal ventilation.

While receiving isoflurane, all 6 patients in our case series were hemodynamically stable and breathing spontaneously. All patients also reacted to endotracheal suctioning despite RASS scores of −4 to −5. Using these clinical parameters, we found it easily possible to evaluate depth of sedation. A clinical means for assessing sedation level was important in our cases because, in this case series, with tidal volumes possibly smaller than anatomical dead space, the end-tidal anesthetic concentration displayed by the gas monitor was inaccurate.

Surprisingly, in this case series infusion pump rates of only 1–3 mL/h were needed. Isoflurane undergoes very little systemic metabolism and is eliminated primarily through pulmonary exhalation. The AnaConDa system recycles 80%–90% of inhaled agents, which facilitates low-infusion volumes for patient sedation. In addition, unlike carbon dioxide, isoflurane is not eliminated via the polymethylpentene membranes of modern oxygenators.15 When using low-minute ventilation under ECMO therapy, therefore, isoflurane consumption will be even lower. This also means that sweep gas from the oxygenator does not contain isoflurane and does not need to be scavenged.

In our case series, we used closed endotracheal suctioning to allow removal of respiratory secretions without loss of airway pressure and workplace contamination with isoflurane. We did not encounter problems with secretions in these patients, although copious secretions interfere with proper function of the AnaConDa device.

We found, as has been previously described,11,16,17 that opioid administration could be reduced after initiating inhaled sedation. Nevertheless, all patients remained deeply sedated as demonstrated by RASS scores of −4 to −5.

Deep sedation and augmented spontaneous breathing were previously described during use of inhaled sedation.13,17,18 Augmented spontaneous breathing may recruit lung tissue in dependent areas, which may be of benefit provided sufficient positive end-expiratory pressure is used to prevent cyclic collapse of alveoli (atelectrauma).19 However, in severe ARDS, bucking against the ventilator should also be prevented. Although some recommend muscular paralysis for this purpose,20 volatile anesthetics also exert some muscle relaxant activity, and, when using isoflurane, we did not observe bucking against the ventilator even in the absence of muscle relaxants.

Interestingly, spontaneous breathing augmented with low 5–10 hPa pressure support was observed in all patients in our case series. Although very small pressure amplitudes were used for controlled mechanical ventilation as well as for pressure support, tidal volume rapidly increased in all patients and was above 180 mL after 24 hours. Possible mechanisms for this effect may include purposeful activity of the diaphragm and improved lung compliance due to anti-inflammatory properties of volatile agents.6,21

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CONCLUSIONS

We found that sedation with inhaled anesthetics was feasible in critically ill patients on ECMO. No adverse events were noted and patients required less opioid and were able to breathe spontaneously while sedated. Experience using this technique is vital for success and safety. In this small series, we did not study survival but did observe some potentially beneficial effects. Further study of the efficacy, practicability, and safety of isoflurane sedation in ECMO patients is warranted.

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ACKNOWLEDGMENTS

The authors thank Karen Schneider for critical revision.

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DISCLOSURES

Name: Andreas Meiser MD.

Contribution: This author helped conceive and design the study, acquire, analyze and interpret the data, draft the manuscript, and revise the manuscript.

Conflicts of Interest: Andreas Meiser received honoraria from Sedana Medical (Uppsala, Sweden) and honoraria for lectures as well as research funding from Pall Medical (Dreieich, Germany).

Name: Hagen Bomberg, MD.

Contribution: This author helped conceive and design the study, acquire, analyze and interpret the data, draft the manuscript, and revise the manuscript.

Conflicts of Interest: None.

Name: Philipp M. Lepper, MD.

Contribution: This author helped revise the manuscript.

Conflicts of Interest: None.

Name: Franziska C. Trudzinski, MD.

Contribution: This author helped conceive and design the study, and revise the manuscript.

Conflicts of Interest: None.

Name: Thomas Volk, MD.

Contribution: This author helped conceive and design the study, and revise the manuscript.

Conflicts of Interest: None.

Name: Heinrich V. Groesdonk, MD.

Contribution: This author helped conceive and design the study, acquire, analyze and interpret the data, draft the manuscript, and revise the manuscript.

Conflicts of Interest: None.

This manuscript was handled by: Avery Tung, MD, FCCM.

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REFERENCES

1. Ullrich R, Lorber C, Röder G, et al. Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS. Anesthesiology. 1999;91:1577–1586.
2. Baron R, Binder A, Biniek R, et al. Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015)–—short version. German Med Sci. 2015;13:Doc19.
3. Celis-Rodríguez E, Birchenall C, de la Cal MÁ, et al; Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva. Clinical practice guidelines for evidence-based management of sedoanalgesia in critically ill adult patients. Med Intensiva.2013;37:519–574.
4. Thomson H, Harper NJ, Parkes A. Use of the AnaConDa anaesthetic delivery system to treat life-threatening asthma. Anaesthesia. 2007;62:295–296.
5. Maltais F, Sovilj M, Goldberg P, Gottfried SB. Respiratory mechanics in status asthmaticus. Effects of inhalational anesthesia. Chest. 1994;106:1401–1406.
6. O’Gara B, Talmor D. Lung protective properties of the volatile anesthetics. Intensive Care Med.2016;42:1487–1489.
7. Kikuchi C, Dosenovic S, Bienengraeber M. Anaesthetics as cardioprotectants: translatability and mechanism. Br J Pharmacol. 2015;172:2051–2061.
8. Englert JA, Macias AA, Amador-Munoz D, et al. Isoflurane ameliorates acute lung injury by preserving epithelial tight junction integrity. Anesthesiology. 2015;123:377–388.
9. Voigtsberger S, Lachmann RA, Leutert AC, et al. Sevoflurane ameliorates gas exchange and attenuates lung damage in experimental lipopolysaccharide-induced lung injury. Anesthesiology. 2009;111:1238–1248.
10. Kong KL, Willatts SM, Prys-Roberts C. Isoflurane compared with midazolam for sedation in the intensive care unit. BMJ (Clinical Research ed). 1989;298:1277–1280.
11. Sackey PV, Martling CR, Granath F, Radell PJ. Prolonged isoflurane sedation of intensive care unit patients with the anesthetic conserving device. Crit Care Med. 2004;32:2241–2246.
12. Bellgardt M, Bomberg H, Herzog-Niescery J, et al. Survival after long-term isoflurane sedation as opposed to intravenous sedation in critically ill surgical patients: Retrospective analysis. Eur J Anaesthesiol. 2016;33:6–13
13. Chabanne R, Perbet S, Futier E, et al. Impact of the anesthetic conserving device on respiratory parameters and work of breathing in critically ill patients under light sedation with sevoflurane. Anesthesiology. 2014;121:808–816.
14. Sturesson LW, Bodelsson M, Jonson B, Malmkvist G. Anaesthetic conserving device AnaConDa: dead space effect and significance for lung protective ventilation. Br J Anaesth. 2014;113:508–514.
15. Prasser C, Zelenka M, Gruber M, Philipp A, Keyser A, Wiesenack C. Elimination of sevoflurane is reduced in plasma-tight compared to conventional membrane oxygenators. Eur J Anaesthesiol. 2008;25:152–157.
16. Mesnil M, Capdevila X, Bringuier S, et al. Long-term sedation in intensive care unit: a randomized comparison between inhaled sevoflurane and intravenous propofol or midazolam. Intensive Care Med. 2011;37:933–941.
17. Migliari M, Bellani G, Rona R, et al. Short-term evaluation of sedation with sevoflurane administered by the anesthetic conserving device in critically ill patients. Intensive Care Med. 2009;35:1240–1246.
18. Meiser A, Laubenthal H. Inhalational anaesthetics in the ICU: theory and practice of inhalational sedation in the ICU, economics, risk-benefit. Best Pract Res Clin Anaesthesiol. 2005;19:523–538.
19. Güldner A, Braune A, Carvalho N, et al. Higher levels of spontaneous breathing induce lung recruitment and reduce global stress/strain in experimental lung injury. Anesthesiology. 2014;120:673–682.
20. Papazian L, Forel JM, Gacouin A, et al; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107–1116.
21. Jabaudon M, Boucher P, Imhoff E, et al. Sevoflurane for sedation in ARDS: a randomized controlled pilot study. Am J Respiratory Crit Care Med. 2016 [Epub ahead of print].
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