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Publications

Journal Article Randomized Controlled Trial Ppublish

PubMed: 42760033 DOI: 10.1111/aas.70336

Haloperidol for Hypoactive and Hyperactive Delirium in ICU Patients-A Post Hoc Bayesian Analysis of the AID-ICU Trial.

Acta Anaesthesiol Scand 70(9):e70336

Authors: Nina C Andersen-Ranberg, Lone Musaeus Poulsen, Anders Perner, Johanna Hästbacka, Matthew Morgan, Giuseppe Citerio, Stine Estrup Damby, Camilla Bekker Mortensen, Marie Oxenbøll Collet, Sven-Olaf Weber, Anne Sofie Andreasen, Morten Bestle, Bülent Uslu, Helle Scharling Pedersen, Louise Gramstrup Nielsen, Kjeld Damgaard, Troels Bek Jensen, Trine Sommer, Nilanjan Dey, Ole Mathiesen, Anders Granholm

Affiliations

  • Department of Anaesthesiology and Intensive Care Medicine, Zealand University Hospital, Køge, Denmark.
  • Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.
  • Department of Intensive Care, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark.
  • Department of Anesthesia and Intensive Care, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Department of Intensive Care, Cardiff University Hospital of Wales, Cardiff, UK.
  • Neuro-Intensive Care, Department of Neurosciences, San Gerardo Hospital, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
  • School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
  • Department of Anaesthesia and Intensive Care, Aalborg University Hospital, Aalborg, Denmark.
  • Department of Anaesthesiology and Intensive Care, Copenhagen University Hospital - Herlev, Herlev, Denmark.
  • Department of Anaesthesiology and Intensive Care, Copenhagen University Hospital - North Zealand, Hillerød, Denmark.
  • Department of Anaesthesiology and Intensive Care Medicine, Zealand University Hospital, Roskilde, Denmark.
  • Department of Anaesthesiology and Intensive Care, Nykøbing Falster Sygehus, Nykøbing Falster, Denmark.
  • Department of Anaesthesiology and Intensive Care, Odense University Hospital, Odense, Denmark.
  • Department of Anaesthesiology and Intensive Care, Hjørring Hospital, Hjørring, Denmark.
  • Department of Anaesthesiology and Intensive Care, Gødstrup Hospital, Herning, Denmark.
  • Department of Anaesthesiology, Hospital of Southern Jutland, Aabenraa, Denmark.
  • Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Abstract

BACKGROUND

Delirium is clinically classified into hypoactive or hyperactive motoric subtypes, which may have different responses to treatment. We assessed heterogeneity in treatment effects according to baseline motoric subtype in the AID-ICU trial, which randomised adult ICU patients with delirium to haloperidol versus placebo.

METHODS

In this post hoc study of the AID-ICU trial, we used adjusted Bayesian linear and logistic regression models to assess potential differential effects of haloperidol on 90-day outcomes according to motor subtypes. Effect estimates are reported as absolute differences within and between subtypes (mean differences (MD)/risk differences (RD) and differences in MDs/RDs), with probabilities of any benefit, any harm and differential effects between subtypes.

RESULTS

Of 987 participants, 540 (54.7%) had hypoactive and 447 (45.3%) had hyperactive delirium at randomisation. Haloperidol was associated with more days alive out of hospital in both subgroups, with a 76.5% probability of a larger intervention effect in those with hyperactive delirium (difference in MDs 2.9 days; 95% CrI -4.8 to 10.6). Similar results were obtained for days alive without delirium/coma and days alive without mechanical ventilation. Haloperidol was associated with lower mortality in both subgroups, with a 73% probability of larger benefit in hyperactive delirium (difference in RDs -3.7%-points; 95% CrI -15.3 to 7.8). We found no relevant differences in serious adverse reactions or use of rescue medications.

CONCLUSION

Compared with placebo, haloperidol was associated with moderate to high probabilities of benefit in both hypoactive and hyperactive delirium, with moderate probabilities of greater effects in hyperactive delirium. Further research is warranted to confirm these results.

EDITORIAL COMMENT

In this post hoc analysis of the AID-ICU trial, haloperidol was associated with moderate to high probabilities of benefit in both hypoactive and hyperactive delirium, with a tendency towards greater treatment effects in hyperactive delirium.

TRIAL REGISTRATION

ClinicalTrials.gov number: NCT03392376; EudraCT number, 2017-003829-15.

MeSH

Delirium, Anesthesiology, Probability, Haloperidol, Therapeutics