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Cognitive improvement during continuous sedation in critically ill, awake and responsive patients: the Acute Neurological ICU Sedation Trial (ANIST)

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Abstract

Introduction

Most anxiolytics and sedative regimens in the intensive care unit (ICU) impair intellectual function, reducing patient autonomy, and often add to patient morbidity. Using an ICU-validated cognitive assessment tool Adapted Cognitive Exam (ACE), we performed a comparison between dexmedetomidine (DEX) and propofol (PRO) to evaluate which sedative regimen offered the least decrement in intellectual capacity.

Methods

This was a prospective, randomized, double-blinded study of 30 awake and intubated brain-injured (BI, n = 18) and non-BI (12) ICU patients. Each patient received fentanyl/PRO and fentanyl/DEX titrated to a calm, awake state using a crossover design. Cognitive testing was performed at each study period using the validated 100-point Hopkins ACE cognitive battery.

Findings

Sedation with PRO diminished adjusted ACE scores (100-point exam) by a mean of −12.4 (95% CI −8.3 to −16.5, p < 0.001) while DEX, in contrast, improved ACE scores (6.8, 95% CI 1.2–12.4, p < 0.018). The difference in the change of ACE score between DEX versus PRO, our primary endpoint, was 19.2 (95% CI 12.3–26.1 p < 0.001) in favor of an improved ACE score on DEX. Patients with BI required less sedative, but effects of PRO and DEX on cognition were not changed. No serious adverse events occurred. Modest bradycardia was noted post hoc with DEX (−7.7 bpm, p < 0.01).

Interpretation

ICU patients may be offered sedation without necessarily compromising arousal or cognition. Alleviation of anxiety and agitation can singly and effectively improve mental engagement and performance if overt forebrain dysfunction is avoided. Higher ACE scores with DEX may be a consequence of the intellect-sparing yet calming effect of this drug.

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Acknowledgments

The authors would like to acknowledge the support of the Johns Hopkins & Bayview pharmacists Laura Wachter, Annette Rowden, Henry Choi, and Jim Monolakis, the neuroscience ICU nurses, especially Gail Biba, Patricia Trionfo, Theresa Blair, and Chris Boileau, and DSMB Committee Chair—Dr. Brent Petty.

Conflict of interest statement

ANIST was an investigator-initiated research study funded in part from a grant from Hospira. There was no input as to hypothesis, trial design, data acquisition, or analysis from the study sponsor. Partial support also was courtesy of The Gannaway Fund, an internal institutional philanthropic gift fund for research.

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Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD, 21287, USA

    Marek A. Mirski & John J. Lewin III

  2. Department of Pharmacy, Johns Hopkins Medicine, Baltimore, USA

    John J. Lewin III

  3. Department of Neurology, Johns Hopkins Medicine, Baltimore, USA

    Marek A. Mirski, Shannon LeDroux & Elizabeth K. Zink

  4. Department of Biostatistics, Johns Hopkins Medicine, Baltimore, USA

    Carol Thompson, Peter Murakami & Michael Griswold

Authors
  1. Marek A. Mirski
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  2. John J. Lewin III
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  3. Shannon LeDroux
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  4. Carol Thompson
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  5. Peter Murakami
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  7. Michael Griswold
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Correspondence to Marek A. Mirski.

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Mirski, M.A., Lewin, J.J., LeDroux, S. et al. Cognitive improvement during continuous sedation in critically ill, awake and responsive patients: the Acute Neurological ICU Sedation Trial (ANIST). Intensive Care Med 36, 1505–1513 (2010). https://doi.org/10.1007/s00134-010-1874-9

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  • DOI: https://doi.org/10.1007/s00134-010-1874-9

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