Elsevier

Journal of Critical Care

Volume 37, February 2017, Pages 1-6
Journal of Critical Care

Sedation/Delirium
Evaluation of sedatives, analgesics, and neuromuscular blocking agents in adults receiving extracorporeal membrane oxygenation,☆☆

https://doi.org/10.1016/j.jcrc.2016.07.020Get rights and content

Abstract

Purpose

The objective of this study was to evaluate the use of sedative, analgesic, and neuromuscular blocking agents (NMBAs) in patients undergoing extracorporeal membrane oxygenation (ECMO) support.

Materials and methods

This was a 2-year, prospective, observational study of adult intensive care unit patients on ECMO support for more than 48 hours.

Results

We analyzed 32 patients, including 15 receiving VA (venoarterial) ECMO and 17 VV (venovenous) ECMO. The median daily dose of benzodiazepines (midazolam equivalents) was 24 mg, and the median daily dose of opioids (fentanyl equivalents) was 3875 μg. There was a moderate negative correlation between the day of ECMO and the median daily benzodiazepine dose (r = −0.5515) and a very weak negative correlation for the median daily opioid dose (r = −0.0053). On average, patients were sedated to Richmond Agitation Sedation Scale scores between 0 and −1. Continuous infusions of opioids, benzodiazepines, propofol, dexmedetomidine, and NMBAs were administered on 404 (85.1%), 199 (41.9%), 95 (20%), 32 (6.7%), and 60 (12.6%) ECMO days, respectively. Patients in the VA arm received a continuous infusion opioid (96.4% vs 81.6% days; P < .001) and benzodiazepine (58.2% vs 37.0% days; P < .001) more frequently.

Conclusions

Patients received relatively low doses of sedatives and analgesics while at a light level of sedation on average. Patients rarely required neuromuscular blockade.

Introduction

Extracorporeal membrane oxygenation (ECMO) is a bridge therapy that can be used temporarily in patients with respiratory or cardiac failure who cannot be managed with conventional therapies [1], [2], [3], [4], [5]. Patients who require this invasive form of support often receive a variety of medications to treat their underlying diagnoses and to facilitate the initiation and maintenance of ECMO therapy. Unlike patients treated with conventional mechanical ventilation, guidelines regarding management of pain, agitation, and delirium (PAD) in patients on ECMO are extremely limited with regard to strategies or assessment [6], [7]. Previous data have shown a need for significant increases in sedative and analgesic doses, as well as the need for neuromuscular blockade [8], [9].

Extracorporeal membrane oxygenation is thought to cause pharmacokinetic changes affecting medications used for (PAD) management, including an increase in volume of distribution secondary to an increase in circulating volume and an alteration in medication clearance [10], [11], [12], [13], [14]. Lower circulating plasma levels of lipophilic medications may be due to sequestration in the ECMO oxygenator and/or the circuit tubing [12], [14], [15], [16], [17], [18], [19]. In addition, the degree of plasma protein binding, the drug molecule size, and the duration of oxygenator use may play a role in decreased levels and clinical effect of drugs [14]. Prolonged use of ECMO may also result in decreased renal perfusion and a subsequent decrease in renal-dependent clearance of medications [20], [21].

We sought to evaluate PAD management, including sedation assessment and utilization of sedatives, analgesics, antipsychotics, and neuromuscular blocking agents (NMBAs), in patients undergoing ECMO support at our institution during a 2-year period. The objective of our study was to test the hypothesis that patients on ECMO would require increased and escalating doses of sedatives and analgesics.

Section snippets

Patient population

Brigham and Women's Hospital is a 793-bed tertiary care facility. The adult ECMO program was established in January 2013 to support the end-stage heart and lung disease programs and provide care to those with acute respiratory failure. It is a multidisciplinary collaboration incorporating members from cardiac surgery, thoracic surgery, pulmonary medicine, anesthesiology, hematology, respiratory therapy, physical therapy, pharmacy, perfusion, and nursing. Extracorporeal membrane oxygenation is

Results

Of the 45 patients screened, 32 patients were analyzed, including 17 patients who received VV ECMO and 15 patients who received VA ECMO. Nine patients were excluded for an ECMO duration of less than 24 hours, and 4 patients were excluded for receiving ECMO for longer than 24 hours before transfer to our institution. The primary indication for VA ECMO was cardiogenic shock, whereas VV ECMO was mainly used as a bridge to lung transplant or in patients with severe ARDS (Table 1). We evaluated a

Discussion

In our analysis, patients required significantly lower doses of opioids and sedatives than previously reported in the literature and did not demonstrate a need for increasing doses throughout the study period [8], [24]. Patients were generally able to be kept at a light level of sedation, with an overall average RASS between 0 and −1. Continuous infusions of opioids were utilized on most ECMO days, but continuous infusions of benzodiazepines were used on less than half of all ECMO days. We

Conclusion

The patients in our study received relatively low doses of sedatives and analgesics. We did not observe an increase in dose requirement over time during ECMO support, possibly due to a multi-odal pharmacologic approach. Overall, patients were not deeply sedated and rarely required neuromuscular blockade. The hypothesis that patients on ECMO require high doses of sedatives and analgesics should be further investigated.

Acknowledgments

We appreciate the expertise of Paul M. Szumita, PharmD, FCCM, BCCCP, BCPS, for his assistance in reviewing this manuscript.

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    The authors of this article have no disclosures concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation

    ☆☆

    These data were presented at the 2016 Society of Critical Care Medicine Congress

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