Sedation and Mobilization during Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Failure: An International Survey Jonathan D. Marhong, MD, FRCPC1; Julian DeBacker, MSc, MD1; Julien Viau-Lapointe, MD2; Laveena Munshi, MD, FRCPC3; Lorenzo Del Sorbo, MD4; Lisa Burry, PharmD5; Eddy Fan, MD, PhD6; Sangeeta Mehta, MD, FRCPC7
Objectives: To characterize sedation, analgesia, delirium, and mobilization practices in patients supported with venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. Design: Cross-sectional electronic survey administered January 2016 to March 2016. Setting: Three-hundred ninety-four extracorporeal membrane oxygenation centers registered with the Extracorporeal Life Support Organization. Subjects: Extracorporeal membrane oxygenation medical directors and program coordinators. Cleveland Clinic Medical Center, Cleveland, OH. Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. 3 Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. 4 Department of Medicine and Interdepartmental Division of Critical Care Medicine, University Health Network and University of Toronto, Toronto, ON, Canada. 5 Department of Pharmacy and Medicine, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. 6 Department of Medicine and Interdepartmental Division of Critical Care Medicine, University Health Network and University of Toronto, Toronto, ON, Canada. 7 Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ ccmjournal). Supported, in part, by Physicians’ Services Incorporated Resident Research Grant. Drs. deBacker, Marhong, and Mehta’s institutions received funding from Physicians’ Services Incorporated. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: [email protected] Copyright © 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000002702 1 2
Critical Care Medicine
Interventions: None. Measurements and Main Results: We analyzed responses from 209 respondents (53%), mostly from academic centers (63%); 41% respondents provide venovenous extracorporeal membrane oxygenation to adults exclusively. Following venovenous extracorporeal membrane oxygenation initiation, 97% respondents administer sedative/analgesic infusions, and the sedation target was “sedated” or “very sedated” for 59%, “calm and cooperative” for 25%, and “unarousable” for 16%. Use of daily sedation interruption and a sedation/analgesia protocol was reported by 51% and 39%, respectively. Midazolam (48%) and propofol (19%) were reported as the most frequently used sedatives; fentanyl (44%) and morphine (20%) the most frequent opioids. Use of a delirium scale was reported by 55% respondents. Physical therapy was reported by 84% respondents, with 41% initiating it within 72 hours after cannulation. Mobilization goals varied from range of motion exercises (81%) to ambulation (22%). The most frequently perceived barriers to mobilization were hemodynamic instability, hypoxemia, and dependency on venovenous extracorporeal membrane oxygenation support. Conclusions: The majority of respondents reported targeting moderate to deep sedation following cannulation, with the use of sedative and opioid infusions. There is considerable variability surrounding early physical therapy and mobilization goals for patients with acute respiratory failure supported by venovenous extracorporeal membrane oxygenation. (Crit Care Med 2017; XX:00–00) Key Words: acute respiratory distress; critical care; extracorporeal life support; intensive care units; sedation; survey
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he increasing use of venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory failure (1, 2) mandates evaluation of cointerventions and supportive therapies shown to influence patient outcome in non-ECMO critically ill patients, including sedation, delirium management, and mobilization. Clinical practice guidelines for the management of pain, agitation, www.ccmjournal.org
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and delirium in critically ill adults offer strong recommendations for sedation minimization strategies such as daily sedation interruption and nurse-directed sedation protocols. Such interventions improve patient outcomes including reducing duration of mechanical ventilation and ICU stay and enabling early mobilization (3, 4). Given their physiologic instability and vascular cannulation, patients are often deeply sedated and immobile during ECMO treatment (4); however, numerous studies in the nonECMO population show that deep sedation and immobilization are associated with adverse effects and worse patient outcomes (5–7). The use of continuous sedative infusions, as opposed to intermittent sedation or no sedation, is an independent predictor of longer duration of mechanical ventilation and longer ICU and hospital stay (8, 9). Deep sedation within 48 hours of intubation is independently associated with longer time to extubation and higher hospital and 180-day mortality (5). Deeply sedated patients are also at risk of having more traumatic recollections of their ICU experience than lightly sedated patients (7). Whether VV-ECMO patients are being managed according to the clinical practice guidelines for the management of pain, agitation, delirium, and mobilization in critically ill adults is not known. The objective of this international survey was to characterize sedation and mobilization practices early following VV-ECMO cannulation in patients with severe acute respiratory failure. These data allow for an appraisal of current practice in relation to clinical practice guidelines for other critically ill populations, serve as a comparator for ECMO centers, and will direct future research and educational interventions.
analgesia, NMB, delirium management, and mobilization in patients treated with VV-ECMO for acute respiratory failure. If a respondent indicated that he/she uses a specific medication, he/she was prompted to indicate the route (IV bolus, IV infusion, IM, oral/enteral) for the selected medication. Similarly, if the participant responded that he/she uses a particular tool to assess sedation or analgesia, he/she was prompted with a subquestion enquiring about the targeted level of sedation and/ or analgesia. The sampling frame consisted of the publicly available list of 394 ELSO-registered ECMO centers (12) (as of January 2016) in 53 countries. For each center, contact information for the medical director (usually an ICU physician) and/or program coordinator is listed. Only one response per institution was included in the analysis. Responses were excluded for any of the following reasons: 1) both the medical director and the program coordinator provided a response from the same center (in this case only, the response from the medical director was included), 2) two medical directors from the same center submitted one response each (the most complete response was used), or 3) an anonymous response was submitted. We converted data from the electronic survey into a database (Microsoft Excel; Microsoft). Descriptive statistics were used to summarize the data.
RESULTS
MATERIALS AND METHODS
Of the 394 ELSO centers contacted, 209 responses (53%) were analyzed from the following geographic regions as outlined in the ELSO directory: North America (54%), Europe (25%), Asia-Pacific (11%), Latin America (5%), South and West Asia, and Africa (5%). Respondent and center characteristics are shown in Table 1.
We conducted an international, cross-sectional survey of ECMO medical directors or program coordinators from all Extracorporeal Life Support Organization (ELSO) reporting centers. Item generation was performed through literature search of sedation, analgesia, neuromuscular blockade (NMB), delirium, and mobilization practices used for ECMO and non-ECMO patients in retrospective and prospective studies, surveys, and clinical practice guidelines (3), our group’s previously validated questionnaire (10), and sampling study authors. Item reduction, formatting, and pretesting were performed among study authors and physicians and allied health professionals (nurses, respiratory therapists, and perfusionists) in the Toronto General Hospital ECMO program. This process resulted in the final survey of 35 items that would have the greatest value for clinicians (supplemental data, Supplemental Digital Content 1, http:// links.lww.com/CCM/C824) (11). The study was approved by the Sinai Health System Research Ethics Board. The electronic questionnaire was generated and distributed using a commercial website (SurveyMonkey; https://www. surveymonkey.com). Participants were considered eligible for survey completion if they were a medical director or program coordinator at a center registered with ELSO and they provide VV-ECMO for acute respiratory failure. We asked respondents about their center’s practices regarding sedation,
Sedation and Analgesia Within the first 48 hours of VV-ECMO initiation, 97% respondents report administering sedatives and/or opioids by continuous infusion and 27% supplement with intermittent boluses. Only 39% of centers reported using a protocol to guide sedation and analgesia. Sedatives reported to be used in more than 75% patients were midazolam (48% respondents), followed by propofol (19%), and dexmedetomidine (11%) (Fig. 1A). Fentanyl is the most frequent opioid (44%), followed by morphine (20%) (Fig. 1B). In centers who manage only neonates and/or pediatric patients (n = 56), the primary sedative used in more than 75% of patients was midazolam (65% respondents), and no respondents indicated propofol as the primary sedative (Fig. 1A). Reported morphine use (45%) exceeds fentanyl (38%) as the primary analgesic in these centers (Fig. 1B). Sedation scales are used in 89% centers (Table 2); most commonly, the Richmond Agitation Sedation Scale (48%). The reported frequency of monitoring with a sedation scale varied, with 35% reporting that they measure sedation scale scores every 4 hours and 28% more frequently. Within the first 48 hours of ECMO initiation, only 28% respondents target a sedation depth described as “calm and cooperative,” and 46%
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Clinical Investigation
Respondent and Center Characteristics TABLE 1.
n (%)
Characteristics
Respondent position (n = 209) Medical director
103 (49)
Coordinator
89 (43)
Other*
17 (8)
Type of hospital (n = 191 ) b
University
121 (63)
Community—Teaching
53 (28)
Community—Nonteaching
17 (9)
Number of ICU Beds (n = 193b) < 20
64 (33)
21–50
66 (34)
> 50
63 (33)
VV-ECMO population treated (n = 193 ) b
Adult only
80 (41)
Pediatric and neonatal
44 (23)
Adult, pediatric, and neonatal
41 (21)
Other combinations
28 (15)
Patients on VV-ECMO per year (n = 192 ) b
< 10
89 (46)
10–20
58 (30)
21–50
33 (17)
> 50
12 (7)
VV-ECMO = venovenous extracorporeal membrane oxygenation. a Other: perfusionist, consultant, cardiothoracic surgeon, etc. b n’s that are < 209 reflect missing data.
target an “unarousable” or “very sedated” patient (Table 2). Daily interruptions of sedative infusions were reported by 51% of respondents, and only 13% of centers that manage only pediatric and/or neonatal patients (Table 2). Overall, 82% of centers report use of a pain scale, most commonly, the Critical Care Pain Observation Tool (20%) or the Nonverbal Pain Scale (18%). The reported frequency of monitoring with a pain scale varied: 37% use scoring every 4 hours and 28% score more frequently. Mobilization The majority of respondents (84%) reported that VV-ECMO patients participate in physical therapy. The time to first physical therapy visit varied depending on patient acuity and attending physician (54% respondents), yet early mobilization (< 72 hr following cannulation) was reported by 41% of respondents (Table 3). Maximal physical therapy goals varied greatly across centers who reported mobilizing their patients and Critical Care Medicine
ranged from passive range of motion exercises in bed (100%) to ambulation (22%) (eFig. 1, Supplemental Digital Content 1, http://links.lww.com/CCM/C824). Passive ROM required the fewest personnel (1, 2), whereas ambulation required three to five personnel. Of respondents who attempt patient ambulation, 72% reported requiring three to five personnel to perform this activity, and a small number of centers (14%) report patient ambulation with one to two personnel (eFig. 2, Supplemental Digital Content 1, http://links.lww.com/CCM/ C824). Only 20% of centers use a protocol to guide mobilization practice. The most significant reported barriers to physical therapy during VV-ECMO were hemodynamic instability (72% respondents), level of dependence on VV-ECMO (49%), and hypoxemia (48%) (Table 3). Delirium was a reported barrier to mobilization for 20% of respondents. Delirium, Physical Restraint, and NMB For delirium management, nonpharmacologic interventions such as family presence (54%), verbal reorientation (41%), and environmental modification (39%) were used more frequently than pharmacologic interventions (Fig. 2). The majority of respondents reported dexmedetomidine (11%), benzodiazepines (10%), and typical (10%) or atypical (8%) antipsychotics as the primary pharmacologic intervention used to treat delirium. Of the antipsychotics, haloperidol (27%) and quetiapine (23%) are most frequently administered, as intermittent boluses (57%) or scheduled standing doses (41%). Use of physical restraints was reported by 83% respondents, with 12% using restraints in more than 75% of ECMO patients. Use of a protocol to guide delirium management was rare (23% respondents). Use of a delirium scale was reported by 55% respondents; of these, 72% use the Confusion Assessment Method for ICU and 8% the Intensive Care Delirium Screening Checklist. Forty-nine percent report delirium assessment once per nursing shift, and 34% report assessment at least once every 4 hours. Nonprocedural NMB use was reported by 85% of respondents (eFig. 3, Supplemental Digital Content 1, http://links. lww.com/CCM/C824). Most respondents (54%) report the duration of NMB varies depending on patient acuity or at the discretion of the attending physician. Only 5% report the duration of NMB typically exceeds 48 hours. The most commonly reported NMBs were cisatracurium (25% respondents), vecuronium (15%), and rocuronium (13%). Only 26% of centers report using a protocol to guide NMB practice.
DISCUSSION In this international, cross-sectional survey of 209 ECMO centers, we found a number of common practices in the management of sedation, analgesia, and mobilization for the care of VV-ECMO patients. 1) Sedation is initially provided predominantly by continuous infusions of benzodiazepines with deep sedation targets. 2) Analgesia is predominantly provided by continuous infusions of fentanyl. 3) Almost all centers provide physical therapy for patients on VV-ECMO, although patient acuity is the major barrier for most respondents and there is www.ccmjournal.org
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(3%) incidence of propofol use following cannulation for ECMO (25). The use of midazolam conflicts with practice guidelines suggesting benzodiazepine avoidance, as they are associated with longer durations of MV (26, 27), ICU length of stay (3), and higher hospital mortality (27) and are an independent risk factor for the development of delirium (28). Studies of nonbenzodiazepine agents in ECMO patients show conflicting results in terms of reducing opioid and benzodiazepine use (16, 20). A randomized trial of 20 ECMO patients demonstrated that the addition of ketamine to standard sedation protocols did not reduce midazolam or opioid use (20). Given ECMO patients’ long ICU stay and the pharmacokinetic alterations of the ECMO circuit (i.e. lipophilic drug sequestration, increased volume of distribution, etc.) (13, 14, 17), the choice of sedative and analgesic is an important consideration. Figure 1. Frequency of commonly used sedative (A) and analgesics (B) within the first 48 hr of starting For example, midazolam, provenovenous extracorporeal membrane oxygenation for acute respiratory failure. *Adult centers, n = 80. ** Pediatric/neonatal centers, n = 56. ***Other sedatives and analgesics: clonidine (n = 8), isoflurane (n = 3), pofol, and fentanyl all demoncodeine (n = 11), ketamine (n = 4), dexmedetomidine (n = 4), and piritramide (n = 5). strate significant sequestration within the ECMO circuit, heterogeneity in timing of physical therapy initiation. 4) The whereas agents such as morphine do not (17, 29). With respect to sedation depth, our results parallel those use of protocols for sedation, analgesia, mobilization, delirium, from a 2010 international survey of 102 ECMO practitioners, and NMB use is infrequent among VV-ECMO centers. which reported deep sedation targets (“unarousable” or “very The literature on sedation management in ECMO patients sedated”) by 41% respondents, light sedation targets (“calm is limited (4, 13–22) and no practice guidelines exist for and cooperative”) by 33% respondents, and the use of sedathis population. Our findings that midazolam and fentanyl, tion interruption daily or intermittently by 43% and 35%, administered as continuous infusions, are the preferred agents respectively (13). Given that many patients transition from for providing sedation and analgesia to VV-ECMO patients deep to light sedation during VV-ECMO treatment (4, 15, 20), are consistent with previous surveys of adult (79% and 45% our survey sought to characterize sedation targets within the respondents, respectively) (13) and pediatric ECMO patients first 48 hours following cannulation, which is the period of (57% and 62%, respectively) (23). In our survey, a large protime the patient is most likely to be deeply sedated (4). At this portion of respondents also reported use of agents such as time point, almost a third of respondents (28%) in our survey dexmedetomidine (74%), propofol (72%), and ketamine targeted a “calm and cooperative” level of sedation, which sug(49%). In pediatric/neonatal centers, none of the respondents gests that many practitioners are trying to minimize sedation reported using propofol as the primary sedative, whereas more very rapidly following cannulation. Some ECMO practitioners than a third of adult centers (37%) use this agent primarily. are even advocating for an “awake ECMO” strategy whereby This may reflect the concern regarding propofol infusion synECMO is initiated early in the course of respiratory failure in drome in younger patients (24) and is corroborated by a mul- order to avoid sedation and intubation and preserve spontaneticenter observational study in children demonstrating a low ous respiration (18). 4
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Clinical Investigation
TABLE 2.
Sedation and Pain Management
Survey Questions
n (%)
Sedation target within first 48 hr of cannulationa (n = 209)
TABLE 3.
Perceived Barriers to Mobilization n (%)
Survey Questions
Time to initiate physical therapy from cannulation (n = 195)
Unarousable
37 (18)
Very sedated
59 (28)
< 72 hr
79 (41)
Sedated
80 (38)
> 72 hr
16 (8)
Calm and cooperative
58 (28)
Varies depending on acuity
87 (45)
Varies depending on ICU physician
19 (10)
Daily sedation interruption All centers (n = 200) Centers caring for adults only (n = 79) Centers caring for pediatrics/neonates only (n = 54)
102 (51) 56 (71) 7 (13)
Sedation scales (n = 198) Do not use a validated scale
22 (11)
Use a validated scale Richmond Agitation Sedation Scale
96 (48)
Ramsay Sedation Scale
15 (8)
Glasgow Coma Scale
13 (7)
Observer’s Assessment of Alertness/Sedation Scale
11 (6)
Sedation-Agitation Scale Other
7 (3) 34 (17)
b
Sedation scale assessment frequency (n = 173) Every 1–2 hr
48 (28)
Every 4 hr
60 (35)
Once per nursing shift
44 (25)
Other
21 (12)
b
Pain scales (n = 196) Do not use a validated scale
36 (18)
Use a validated scale Critical Care Pain Observation Tool
39 (20)
Nonverbal Pain Scale
35 (18)
Behavioral Pain Scale
28 (14)
Pain Behavioral Assessment Tool
11 (6)
Neonatal Pain, Agitation and Sedation Scale Other
b
9 (5) 38 (19)
Pain scale frequency (n = 163) Every 1–2 hr
46 (28)
Every 4 hr
60 (37)
Once per nursing shift
28 (17)
Other
29 (18)
b
Respondents could select > 1 sedation target. b A full list of sedation/pain scales and frequency of assessment are displayed in Supplemental Digital Content 1: Electronic Survey. Some respondents did not provide response for some questions, which accounts for variation in n. a
Critical Care Medicine
Patients do not participate in physical therapy
32 (16)
Barriers to mobilization (n = 190) Hemodynamic instability
136 (72)
Level of dependence on ECMO
94 (49)
Hypoxemia
91 (48)
Femoral cannulation
74 (39)
Fear of unintentional decannulation
73 (38)
Being on venovenous ECMO
56 (29)
Lack of personnel
48 (25)
Delirium
39 (20)
Patients deeply sedated for 72 hr
27 (14)
Other
26 (14)
a
None are barriers to mobilization
5 (3)
ECMO = extracorporeal membrane oxygenation. a Patient age (child or neonate) was the most common “other” barrier to mobilization n = 13 (7%). Multiple responses per survey question could be selected.
The opportunity for mobilization is a clear advantage of minimizing sedation; however, there are no prospective studies evaluating active mobilization in patients on VV-ECMO. A single-center retrospective study of 100 patients (nine with acute respiratory distress syndrome [ARDS]) concluded that active physical therapy could be implemented safely in patients on a variety of ECMO configurations (30). The benefits of early mobilization in mechanically ventilated patients are inconclusive. Although several prospective studies demonstrate improved functional outcomes at hospital discharge, a shorter duration of delirium, more ventilator-free days (31), and shorter ICU and hospital lengths of stay (32), others show no difference in length of stay (33) or long-term physical performance (34) compared with usual care. Although almost half of respondents (41%) aim to have VV-ECMO patients participate in physical therapy within 72 hours of cannulation, 16% respondents do not engage patients in any physical therapy during VV-ECMO treatment. These data illustrates important center variability in timing of physical therapy, which could potentially have an impact on patient outcomes. Early and intensive mobilization in ECMO patients may be particularly beneficial given their prolonged ICU stay, and it is conceivable that, if acuity is not a barrier, patients may participate in physical therapy early following cannulation. www.ccmjournal.org
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Figure 2. Frequency of commonly used nonpharmacologic (A) and pharmacologic therapies (B) for delirium management and commonly used antipsychotics (C) during the first 48 hr of starting venovenous extracorporeal membrane oxygenation for acute respiratory failure. *Other reported pharmacologic therapies: clonidine (n = 4). ** Other reported antipsychotics: ziprasidone (n = 2), aripiprazole (n = 2).
Delirium was reported by 20% of respondents as a barrier to mobilization, possibly reflecting clinician concerns about device removal in ECMO patients with large-bore vascular cannulae. A systematic review of 42 studies and 16,595 patients identified delirium in 32% critically ill patients, which was associated with higher hospital mortality, and longer duration of MV, and ICU and hospital lengths of stay (35). Other adverse outcomes associated with ICU delirium include increased rates of self-extubation, catheter removal, long-term cognitive dysfunction, and higher mortality (36, 37). In a retrospective study of 45 VV-ECMO patients with ARDS, 79% had a positive delirium screen while on ECMO, but there was only one (2%) self-extubation and three peripheral IVs removed (7%) (4). Although a 2006 survey of 273 Canadian intensivists reported infrequent use of delirium scales (3.7%) (10), 55% of respondents in our survey report the routine use of a delirium assessment tool. Nonpharmacologic interventions were frequently employed by clinicians who recognize delirium among VV-ECMO patients, and a wide variation in pharmacologic interventions were commonly employed The robust response from 209 international ECMO centers provides a snapshot of numerous aspects of sedation 6
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management across the world. Many of the survey questions focus on patient management immediately following ECMO cannulation—a critical period of profound hypoxemia that may necessitate deep sedation targets. Thus, the results of our survey represent sedation practices when these patients may be most unstable. Furthermore, the survey describes the point prevalence of respondents’ use of current evidence-based strategies in the management of sedation, delirium, and mobilization. Our study has limitations. Selection bias may exist as the characteristics of the nonresponding centers (47%) cannot be determined. Reported practice may differ from actual practice, and the dynamic changes in patient management throughout VV-ECMO treatment could not be captured by our survey. Finally, we did not explore the criteria for VV-ECMO initiation, nor the rationale for sedative/analgesic choices.
CONCLUSIONS
This international survey describes current sedation practice among ECMO centers, with an emphasis on sedation, analgesia, and mobilization early after cannulation, for patients supported by VV-ECMO for acute respiratory failure. The majority of centers reported targeting moderate to deep sedation with the use of continuous midazolam infusions. A minority of respondents reported mobilizing these patients out of bed, with illness severity the most frequently perceived barrier to mobilization. Future investigations in this population should focus on minimizing sedation, safe mobilization, and developing objective criteria to help guide the transition from deep sedation to more wakeful states following cannulation.
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Clinical Investigation 4. deBacker J, Tamberg E, O’Neill L, et al: 36th International Symposium on Intensive Care and Emergency Medicine. Crit Care 2016; 20(Suppl 2):94 5. Shehabi Y, Chan L, Kadiman S, et al; Sedation Practice in Intensive Care Evaluation (SPICE) Study Group investigators: Sedation depth and long-term mortality in mechanically ventilated critically ill adults: A prospective longitudinal multicentre cohort study. Intensive Care Med 2013; 39:910–918 6. Balzer F, Weiß B, Kumpf O, et al: Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care 2015; 19:197 7. Treggiari MM, Romand JA, Yanez ND, et al: Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med 2009; 37:2527–2534 8. Arroliga A, Frutos-Vivar F, Hall J, et al; International Mechanical Ventilation Study Group: Use of sedatives and neuromuscular blockers in a cohort of patients receiving mechanical ventilation. Chest 2005; 128:496–506 9. Kollef MH, Levy NT, Ahrens TS, et al: The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest 1998; 114:541–548 10. Mehta S, Burry L, Fischer S, et al; Canadian Critical Care Trials Group: Canadian survey of the use of sedatives, analgesics, and neuromuscular blocking agents in critically ill patients. Crit Care Med 2006; 34:374–380 11. Burns KE, Duffett M, Kho ME, et al; ACCADEMY Group: A guide for the design and conduct of self-administered surveys of clinicians. CMAJ 2008; 179:245–252 12. ELSO: Extracorporeal Life Support Organization - ECMO and ECLS > Members > Center Directory, 2016. Available at: https://www.elso. org/Members/CenterDirectory.aspx 13. Buscher H, Vaidiyanathan S, Al-Soufi S, et al: Sedation practice in veno-venous extracorporeal membrane oxygenation: An international survey. ASAIO J 2013; 59:636–641 14. Shekar K, Roberts JA, Mullany DV, et al: Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardiorespiratory failure. Anaesth Intensive Care 2012; 40:648–655 15. Lindén V, Palmér K, Reinhard J, et al: High survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation. Intensive Care Med 2000; 26:1630–1637 16. Tellor B, Shin N, Graetz TJ, et al: Ketamine infusion for patients receiving extracorporeal membrane oxygenation support: A case series. F1000Research 2015; 4:1630 17. Shekar K, Roberts JA, Mcdonald CI, et al: Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care 2012; 16:R194 18. Langer T, Santini A, Bottino N, et al: “Awake” extracorporeal membrane oxygenation (ECMO): Pathophysiology, technical considerations, and clinical pioneering. Crit Care 2016; 20:150 19. Verkoyen K, Schildhauer TA, Strauch JT, et al: The effects of propofol and isoflurane sedation on the outcomes of surgical patients receiving extracorporeal membrane oxygenation. ASAIO J 2017; 63:174–178 20. Dzierba AL, Brodie D, Bacchetta M, et al: Ketamine use in sedation management in patients receiving extracorporeal membrane oxygenation. Intensive Care Med 2016; 42:1822–1823
Critical Care Medicine
21. Anton-Martin P, Modem V, Taylor D, et al: A retrospective study of sedation and analgesic requirements of pediatric patients on extracorporeal membrane oxygenation (ECMO) from a single-center experience. Perfusion 2017; 32:183–191 22. DeGrado JR, Hohlfelder B, Ritchie BM, et al: Evaluation of sedatives, analgesics, and neuromuscular blocking agents in adults receiving extracorporeal membrane oxygenation. J Crit Care 2017; 37:1–6 23. DeBerry BB, Lynch JE, Chernin JM, et al: A survey for pain and sedation medications in pediatric patients during extracorporeal membrane oxygenation. Perfusion 2005; 20:139–143 24. Okamoto MP, Kawaguchi DL, Amin AN: Evaluation of propofol infusion syndrome in pediatric intensive care. Am J Health Syst Pharm 2003; 60:2007–2014 25. Schneider JB, Sweberg T, Asaro LA, et al; Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) Study Investigators: Sedation management in children supported on extracorporeal membrane oxygenation for acute respiratory failure. Crit Care Med 2017 [Epub ahead of print] 26. Ho KM, Ng JY: The use of propofol for medium and long-term sedation in critically ill adult patients: A meta-analysis. Intensive Care Med 2008; 34:1969–1979 27. Lonardo NW, Mone MC, Nirula R, et al: Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care Med 2014; 189:1383–1394 28. Pandharipande P, Cotton BA, Shintani A, et al: Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma 2008; 65:34–41 29. Lemaitre F, Hasni N, Leprince P, et al: Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood. Crit Care 2015; 19:40 30. Abrams D, Javidfar J, Farrand E, et al: Early mobilization of patients receiving extracorporeal membrane oxygenation: A retrospective cohort study. Crit Care 2014; 18:R38 31. Schweickert WD, Pohlman MC, Pohlman AS, et al: Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet 2009; 373:1874–1882 32. Morris PE, Goad A, Thompson C, et al: Early intensive care unit mobility therapy in the treatment of acute respiratory failure. Crit Care Med 2008; 36:2238–2243 33. Morris PE, Berry MJ, Files DC, et al: Standardized rehabilitation and hospital length of stay among patients with acute respiratory failure: A randomized clinical trial. JAMA 2016; 315:2694–2702 34. Moss M, Nordon-Craft A, Malone D, et al: A randomized trial of an intensive physical therapy program for patients with acute respiratory failure. Am J Respir Crit Care Med 2016; 193:1101–1110 35. Salluh JI, Wang H, Schneider EB, et al: Outcome of delirium in critically ill patients: Systematic review and meta-analysis. BMJ 2015; 350:h2538 36. Dubois MJ, Bergeron N, Dumont M, et al: Delirium in an intensive care unit: A study of risk factors. Intensive Care Med 2001; 27: 1297–1304 37. Ely EW, Shintani A, Truman B, et al: Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004; 291:1753–1762
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Objectives: To characterize sedation, analgesia, delirium, and mobilization practices in patients supported with venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. Design: Cross-sectional electronic survey administered January 2016 to March 2016. Setting: Three-hundred ninety-four extracorporeal membrane oxygenation centers registered with the Extracorporeal Life Support Organization. Subjects: Extracorporeal membrane oxygenation medical directors and program coordinators. Cleveland Clinic Medical Center, Cleveland, OH. Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. 3 Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. 4 Department of Medicine and Interdepartmental Division of Critical Care Medicine, University Health Network and University of Toronto, Toronto, ON, Canada. 5 Department of Pharmacy and Medicine, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. 6 Department of Medicine and Interdepartmental Division of Critical Care Medicine, University Health Network and University of Toronto, Toronto, ON, Canada. 7 Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ ccmjournal). Supported, in part, by Physicians’ Services Incorporated Resident Research Grant. Drs. deBacker, Marhong, and Mehta’s institutions received funding from Physicians’ Services Incorporated. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: [email protected] Copyright © 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000002702 1 2
Critical Care Medicine
Interventions: None. Measurements and Main Results: We analyzed responses from 209 respondents (53%), mostly from academic centers (63%); 41% respondents provide venovenous extracorporeal membrane oxygenation to adults exclusively. Following venovenous extracorporeal membrane oxygenation initiation, 97% respondents administer sedative/analgesic infusions, and the sedation target was “sedated” or “very sedated” for 59%, “calm and cooperative” for 25%, and “unarousable” for 16%. Use of daily sedation interruption and a sedation/analgesia protocol was reported by 51% and 39%, respectively. Midazolam (48%) and propofol (19%) were reported as the most frequently used sedatives; fentanyl (44%) and morphine (20%) the most frequent opioids. Use of a delirium scale was reported by 55% respondents. Physical therapy was reported by 84% respondents, with 41% initiating it within 72 hours after cannulation. Mobilization goals varied from range of motion exercises (81%) to ambulation (22%). The most frequently perceived barriers to mobilization were hemodynamic instability, hypoxemia, and dependency on venovenous extracorporeal membrane oxygenation support. Conclusions: The majority of respondents reported targeting moderate to deep sedation following cannulation, with the use of sedative and opioid infusions. There is considerable variability surrounding early physical therapy and mobilization goals for patients with acute respiratory failure supported by venovenous extracorporeal membrane oxygenation. (Crit Care Med 2017; XX:00–00) Key Words: acute respiratory distress; critical care; extracorporeal life support; intensive care units; sedation; survey
T
he increasing use of venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory failure (1, 2) mandates evaluation of cointerventions and supportive therapies shown to influence patient outcome in non-ECMO critically ill patients, including sedation, delirium management, and mobilization. Clinical practice guidelines for the management of pain, agitation, www.ccmjournal.org
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and delirium in critically ill adults offer strong recommendations for sedation minimization strategies such as daily sedation interruption and nurse-directed sedation protocols. Such interventions improve patient outcomes including reducing duration of mechanical ventilation and ICU stay and enabling early mobilization (3, 4). Given their physiologic instability and vascular cannulation, patients are often deeply sedated and immobile during ECMO treatment (4); however, numerous studies in the nonECMO population show that deep sedation and immobilization are associated with adverse effects and worse patient outcomes (5–7). The use of continuous sedative infusions, as opposed to intermittent sedation or no sedation, is an independent predictor of longer duration of mechanical ventilation and longer ICU and hospital stay (8, 9). Deep sedation within 48 hours of intubation is independently associated with longer time to extubation and higher hospital and 180-day mortality (5). Deeply sedated patients are also at risk of having more traumatic recollections of their ICU experience than lightly sedated patients (7). Whether VV-ECMO patients are being managed according to the clinical practice guidelines for the management of pain, agitation, delirium, and mobilization in critically ill adults is not known. The objective of this international survey was to characterize sedation and mobilization practices early following VV-ECMO cannulation in patients with severe acute respiratory failure. These data allow for an appraisal of current practice in relation to clinical practice guidelines for other critically ill populations, serve as a comparator for ECMO centers, and will direct future research and educational interventions.
analgesia, NMB, delirium management, and mobilization in patients treated with VV-ECMO for acute respiratory failure. If a respondent indicated that he/she uses a specific medication, he/she was prompted to indicate the route (IV bolus, IV infusion, IM, oral/enteral) for the selected medication. Similarly, if the participant responded that he/she uses a particular tool to assess sedation or analgesia, he/she was prompted with a subquestion enquiring about the targeted level of sedation and/ or analgesia. The sampling frame consisted of the publicly available list of 394 ELSO-registered ECMO centers (12) (as of January 2016) in 53 countries. For each center, contact information for the medical director (usually an ICU physician) and/or program coordinator is listed. Only one response per institution was included in the analysis. Responses were excluded for any of the following reasons: 1) both the medical director and the program coordinator provided a response from the same center (in this case only, the response from the medical director was included), 2) two medical directors from the same center submitted one response each (the most complete response was used), or 3) an anonymous response was submitted. We converted data from the electronic survey into a database (Microsoft Excel; Microsoft). Descriptive statistics were used to summarize the data.
RESULTS
MATERIALS AND METHODS
Of the 394 ELSO centers contacted, 209 responses (53%) were analyzed from the following geographic regions as outlined in the ELSO directory: North America (54%), Europe (25%), Asia-Pacific (11%), Latin America (5%), South and West Asia, and Africa (5%). Respondent and center characteristics are shown in Table 1.
We conducted an international, cross-sectional survey of ECMO medical directors or program coordinators from all Extracorporeal Life Support Organization (ELSO) reporting centers. Item generation was performed through literature search of sedation, analgesia, neuromuscular blockade (NMB), delirium, and mobilization practices used for ECMO and non-ECMO patients in retrospective and prospective studies, surveys, and clinical practice guidelines (3), our group’s previously validated questionnaire (10), and sampling study authors. Item reduction, formatting, and pretesting were performed among study authors and physicians and allied health professionals (nurses, respiratory therapists, and perfusionists) in the Toronto General Hospital ECMO program. This process resulted in the final survey of 35 items that would have the greatest value for clinicians (supplemental data, Supplemental Digital Content 1, http:// links.lww.com/CCM/C824) (11). The study was approved by the Sinai Health System Research Ethics Board. The electronic questionnaire was generated and distributed using a commercial website (SurveyMonkey; https://www. surveymonkey.com). Participants were considered eligible for survey completion if they were a medical director or program coordinator at a center registered with ELSO and they provide VV-ECMO for acute respiratory failure. We asked respondents about their center’s practices regarding sedation,
Sedation and Analgesia Within the first 48 hours of VV-ECMO initiation, 97% respondents report administering sedatives and/or opioids by continuous infusion and 27% supplement with intermittent boluses. Only 39% of centers reported using a protocol to guide sedation and analgesia. Sedatives reported to be used in more than 75% patients were midazolam (48% respondents), followed by propofol (19%), and dexmedetomidine (11%) (Fig. 1A). Fentanyl is the most frequent opioid (44%), followed by morphine (20%) (Fig. 1B). In centers who manage only neonates and/or pediatric patients (n = 56), the primary sedative used in more than 75% of patients was midazolam (65% respondents), and no respondents indicated propofol as the primary sedative (Fig. 1A). Reported morphine use (45%) exceeds fentanyl (38%) as the primary analgesic in these centers (Fig. 1B). Sedation scales are used in 89% centers (Table 2); most commonly, the Richmond Agitation Sedation Scale (48%). The reported frequency of monitoring with a sedation scale varied, with 35% reporting that they measure sedation scale scores every 4 hours and 28% more frequently. Within the first 48 hours of ECMO initiation, only 28% respondents target a sedation depth described as “calm and cooperative,” and 46%
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Clinical Investigation
Respondent and Center Characteristics TABLE 1.
n (%)
Characteristics
Respondent position (n = 209) Medical director
103 (49)
Coordinator
89 (43)
Other*
17 (8)
Type of hospital (n = 191 ) b
University
121 (63)
Community—Teaching
53 (28)
Community—Nonteaching
17 (9)
Number of ICU Beds (n = 193b) < 20
64 (33)
21–50
66 (34)
> 50
63 (33)
VV-ECMO population treated (n = 193 ) b
Adult only
80 (41)
Pediatric and neonatal
44 (23)
Adult, pediatric, and neonatal
41 (21)
Other combinations
28 (15)
Patients on VV-ECMO per year (n = 192 ) b
< 10
89 (46)
10–20
58 (30)
21–50
33 (17)
> 50
12 (7)
VV-ECMO = venovenous extracorporeal membrane oxygenation. a Other: perfusionist, consultant, cardiothoracic surgeon, etc. b n’s that are < 209 reflect missing data.
target an “unarousable” or “very sedated” patient (Table 2). Daily interruptions of sedative infusions were reported by 51% of respondents, and only 13% of centers that manage only pediatric and/or neonatal patients (Table 2). Overall, 82% of centers report use of a pain scale, most commonly, the Critical Care Pain Observation Tool (20%) or the Nonverbal Pain Scale (18%). The reported frequency of monitoring with a pain scale varied: 37% use scoring every 4 hours and 28% score more frequently. Mobilization The majority of respondents (84%) reported that VV-ECMO patients participate in physical therapy. The time to first physical therapy visit varied depending on patient acuity and attending physician (54% respondents), yet early mobilization (< 72 hr following cannulation) was reported by 41% of respondents (Table 3). Maximal physical therapy goals varied greatly across centers who reported mobilizing their patients and Critical Care Medicine
ranged from passive range of motion exercises in bed (100%) to ambulation (22%) (eFig. 1, Supplemental Digital Content 1, http://links.lww.com/CCM/C824). Passive ROM required the fewest personnel (1, 2), whereas ambulation required three to five personnel. Of respondents who attempt patient ambulation, 72% reported requiring three to five personnel to perform this activity, and a small number of centers (14%) report patient ambulation with one to two personnel (eFig. 2, Supplemental Digital Content 1, http://links.lww.com/CCM/ C824). Only 20% of centers use a protocol to guide mobilization practice. The most significant reported barriers to physical therapy during VV-ECMO were hemodynamic instability (72% respondents), level of dependence on VV-ECMO (49%), and hypoxemia (48%) (Table 3). Delirium was a reported barrier to mobilization for 20% of respondents. Delirium, Physical Restraint, and NMB For delirium management, nonpharmacologic interventions such as family presence (54%), verbal reorientation (41%), and environmental modification (39%) were used more frequently than pharmacologic interventions (Fig. 2). The majority of respondents reported dexmedetomidine (11%), benzodiazepines (10%), and typical (10%) or atypical (8%) antipsychotics as the primary pharmacologic intervention used to treat delirium. Of the antipsychotics, haloperidol (27%) and quetiapine (23%) are most frequently administered, as intermittent boluses (57%) or scheduled standing doses (41%). Use of physical restraints was reported by 83% respondents, with 12% using restraints in more than 75% of ECMO patients. Use of a protocol to guide delirium management was rare (23% respondents). Use of a delirium scale was reported by 55% respondents; of these, 72% use the Confusion Assessment Method for ICU and 8% the Intensive Care Delirium Screening Checklist. Forty-nine percent report delirium assessment once per nursing shift, and 34% report assessment at least once every 4 hours. Nonprocedural NMB use was reported by 85% of respondents (eFig. 3, Supplemental Digital Content 1, http://links. lww.com/CCM/C824). Most respondents (54%) report the duration of NMB varies depending on patient acuity or at the discretion of the attending physician. Only 5% report the duration of NMB typically exceeds 48 hours. The most commonly reported NMBs were cisatracurium (25% respondents), vecuronium (15%), and rocuronium (13%). Only 26% of centers report using a protocol to guide NMB practice.
DISCUSSION In this international, cross-sectional survey of 209 ECMO centers, we found a number of common practices in the management of sedation, analgesia, and mobilization for the care of VV-ECMO patients. 1) Sedation is initially provided predominantly by continuous infusions of benzodiazepines with deep sedation targets. 2) Analgesia is predominantly provided by continuous infusions of fentanyl. 3) Almost all centers provide physical therapy for patients on VV-ECMO, although patient acuity is the major barrier for most respondents and there is www.ccmjournal.org
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(3%) incidence of propofol use following cannulation for ECMO (25). The use of midazolam conflicts with practice guidelines suggesting benzodiazepine avoidance, as they are associated with longer durations of MV (26, 27), ICU length of stay (3), and higher hospital mortality (27) and are an independent risk factor for the development of delirium (28). Studies of nonbenzodiazepine agents in ECMO patients show conflicting results in terms of reducing opioid and benzodiazepine use (16, 20). A randomized trial of 20 ECMO patients demonstrated that the addition of ketamine to standard sedation protocols did not reduce midazolam or opioid use (20). Given ECMO patients’ long ICU stay and the pharmacokinetic alterations of the ECMO circuit (i.e. lipophilic drug sequestration, increased volume of distribution, etc.) (13, 14, 17), the choice of sedative and analgesic is an important consideration. Figure 1. Frequency of commonly used sedative (A) and analgesics (B) within the first 48 hr of starting For example, midazolam, provenovenous extracorporeal membrane oxygenation for acute respiratory failure. *Adult centers, n = 80. ** Pediatric/neonatal centers, n = 56. ***Other sedatives and analgesics: clonidine (n = 8), isoflurane (n = 3), pofol, and fentanyl all demoncodeine (n = 11), ketamine (n = 4), dexmedetomidine (n = 4), and piritramide (n = 5). strate significant sequestration within the ECMO circuit, heterogeneity in timing of physical therapy initiation. 4) The whereas agents such as morphine do not (17, 29). With respect to sedation depth, our results parallel those use of protocols for sedation, analgesia, mobilization, delirium, from a 2010 international survey of 102 ECMO practitioners, and NMB use is infrequent among VV-ECMO centers. which reported deep sedation targets (“unarousable” or “very The literature on sedation management in ECMO patients sedated”) by 41% respondents, light sedation targets (“calm is limited (4, 13–22) and no practice guidelines exist for and cooperative”) by 33% respondents, and the use of sedathis population. Our findings that midazolam and fentanyl, tion interruption daily or intermittently by 43% and 35%, administered as continuous infusions, are the preferred agents respectively (13). Given that many patients transition from for providing sedation and analgesia to VV-ECMO patients deep to light sedation during VV-ECMO treatment (4, 15, 20), are consistent with previous surveys of adult (79% and 45% our survey sought to characterize sedation targets within the respondents, respectively) (13) and pediatric ECMO patients first 48 hours following cannulation, which is the period of (57% and 62%, respectively) (23). In our survey, a large protime the patient is most likely to be deeply sedated (4). At this portion of respondents also reported use of agents such as time point, almost a third of respondents (28%) in our survey dexmedetomidine (74%), propofol (72%), and ketamine targeted a “calm and cooperative” level of sedation, which sug(49%). In pediatric/neonatal centers, none of the respondents gests that many practitioners are trying to minimize sedation reported using propofol as the primary sedative, whereas more very rapidly following cannulation. Some ECMO practitioners than a third of adult centers (37%) use this agent primarily. are even advocating for an “awake ECMO” strategy whereby This may reflect the concern regarding propofol infusion synECMO is initiated early in the course of respiratory failure in drome in younger patients (24) and is corroborated by a mul- order to avoid sedation and intubation and preserve spontaneticenter observational study in children demonstrating a low ous respiration (18). 4
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Clinical Investigation
TABLE 2.
Sedation and Pain Management
Survey Questions
n (%)
Sedation target within first 48 hr of cannulationa (n = 209)
TABLE 3.
Perceived Barriers to Mobilization n (%)
Survey Questions
Time to initiate physical therapy from cannulation (n = 195)
Unarousable
37 (18)
Very sedated
59 (28)
< 72 hr
79 (41)
Sedated
80 (38)
> 72 hr
16 (8)
Calm and cooperative
58 (28)
Varies depending on acuity
87 (45)
Varies depending on ICU physician
19 (10)
Daily sedation interruption All centers (n = 200) Centers caring for adults only (n = 79) Centers caring for pediatrics/neonates only (n = 54)
102 (51) 56 (71) 7 (13)
Sedation scales (n = 198) Do not use a validated scale
22 (11)
Use a validated scale Richmond Agitation Sedation Scale
96 (48)
Ramsay Sedation Scale
15 (8)
Glasgow Coma Scale
13 (7)
Observer’s Assessment of Alertness/Sedation Scale
11 (6)
Sedation-Agitation Scale Other
7 (3) 34 (17)
b
Sedation scale assessment frequency (n = 173) Every 1–2 hr
48 (28)
Every 4 hr
60 (35)
Once per nursing shift
44 (25)
Other
21 (12)
b
Pain scales (n = 196) Do not use a validated scale
36 (18)
Use a validated scale Critical Care Pain Observation Tool
39 (20)
Nonverbal Pain Scale
35 (18)
Behavioral Pain Scale
28 (14)
Pain Behavioral Assessment Tool
11 (6)
Neonatal Pain, Agitation and Sedation Scale Other
b
9 (5) 38 (19)
Pain scale frequency (n = 163) Every 1–2 hr
46 (28)
Every 4 hr
60 (37)
Once per nursing shift
28 (17)
Other
29 (18)
b
Respondents could select > 1 sedation target. b A full list of sedation/pain scales and frequency of assessment are displayed in Supplemental Digital Content 1: Electronic Survey. Some respondents did not provide response for some questions, which accounts for variation in n. a
Critical Care Medicine
Patients do not participate in physical therapy
32 (16)
Barriers to mobilization (n = 190) Hemodynamic instability
136 (72)
Level of dependence on ECMO
94 (49)
Hypoxemia
91 (48)
Femoral cannulation
74 (39)
Fear of unintentional decannulation
73 (38)
Being on venovenous ECMO
56 (29)
Lack of personnel
48 (25)
Delirium
39 (20)
Patients deeply sedated for 72 hr
27 (14)
Other
26 (14)
a
None are barriers to mobilization
5 (3)
ECMO = extracorporeal membrane oxygenation. a Patient age (child or neonate) was the most common “other” barrier to mobilization n = 13 (7%). Multiple responses per survey question could be selected.
The opportunity for mobilization is a clear advantage of minimizing sedation; however, there are no prospective studies evaluating active mobilization in patients on VV-ECMO. A single-center retrospective study of 100 patients (nine with acute respiratory distress syndrome [ARDS]) concluded that active physical therapy could be implemented safely in patients on a variety of ECMO configurations (30). The benefits of early mobilization in mechanically ventilated patients are inconclusive. Although several prospective studies demonstrate improved functional outcomes at hospital discharge, a shorter duration of delirium, more ventilator-free days (31), and shorter ICU and hospital lengths of stay (32), others show no difference in length of stay (33) or long-term physical performance (34) compared with usual care. Although almost half of respondents (41%) aim to have VV-ECMO patients participate in physical therapy within 72 hours of cannulation, 16% respondents do not engage patients in any physical therapy during VV-ECMO treatment. These data illustrates important center variability in timing of physical therapy, which could potentially have an impact on patient outcomes. Early and intensive mobilization in ECMO patients may be particularly beneficial given their prolonged ICU stay, and it is conceivable that, if acuity is not a barrier, patients may participate in physical therapy early following cannulation. www.ccmjournal.org
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Marhong et al
Figure 2. Frequency of commonly used nonpharmacologic (A) and pharmacologic therapies (B) for delirium management and commonly used antipsychotics (C) during the first 48 hr of starting venovenous extracorporeal membrane oxygenation for acute respiratory failure. *Other reported pharmacologic therapies: clonidine (n = 4). ** Other reported antipsychotics: ziprasidone (n = 2), aripiprazole (n = 2).
Delirium was reported by 20% of respondents as a barrier to mobilization, possibly reflecting clinician concerns about device removal in ECMO patients with large-bore vascular cannulae. A systematic review of 42 studies and 16,595 patients identified delirium in 32% critically ill patients, which was associated with higher hospital mortality, and longer duration of MV, and ICU and hospital lengths of stay (35). Other adverse outcomes associated with ICU delirium include increased rates of self-extubation, catheter removal, long-term cognitive dysfunction, and higher mortality (36, 37). In a retrospective study of 45 VV-ECMO patients with ARDS, 79% had a positive delirium screen while on ECMO, but there was only one (2%) self-extubation and three peripheral IVs removed (7%) (4). Although a 2006 survey of 273 Canadian intensivists reported infrequent use of delirium scales (3.7%) (10), 55% of respondents in our survey report the routine use of a delirium assessment tool. Nonpharmacologic interventions were frequently employed by clinicians who recognize delirium among VV-ECMO patients, and a wide variation in pharmacologic interventions were commonly employed The robust response from 209 international ECMO centers provides a snapshot of numerous aspects of sedation 6
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management across the world. Many of the survey questions focus on patient management immediately following ECMO cannulation—a critical period of profound hypoxemia that may necessitate deep sedation targets. Thus, the results of our survey represent sedation practices when these patients may be most unstable. Furthermore, the survey describes the point prevalence of respondents’ use of current evidence-based strategies in the management of sedation, delirium, and mobilization. Our study has limitations. Selection bias may exist as the characteristics of the nonresponding centers (47%) cannot be determined. Reported practice may differ from actual practice, and the dynamic changes in patient management throughout VV-ECMO treatment could not be captured by our survey. Finally, we did not explore the criteria for VV-ECMO initiation, nor the rationale for sedative/analgesic choices.
CONCLUSIONS
This international survey describes current sedation practice among ECMO centers, with an emphasis on sedation, analgesia, and mobilization early after cannulation, for patients supported by VV-ECMO for acute respiratory failure. The majority of centers reported targeting moderate to deep sedation with the use of continuous midazolam infusions. A minority of respondents reported mobilizing these patients out of bed, with illness severity the most frequently perceived barrier to mobilization. Future investigations in this population should focus on minimizing sedation, safe mobilization, and developing objective criteria to help guide the transition from deep sedation to more wakeful states following cannulation.
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