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Gender differences in the use of atypical antipsychotic medications for ICU delirium

Critical Care201822:220

https://doi.org/10.1186/s13054-018-2143-5

  • Received: 18 July 2018
  • Accepted: 30 July 2018
  • Published:

Intensive care unit (ICU) delirium, an acute fluctuating disturbance of cognition associated with critical illness, is associated with increased mortality, ICU length of stay, mechanical ventilation, and hospital costs [13]. Despite a link to increased long-term mortality, atypical antipsychotic medications (AAP) are frequently administered for the treatment of ICU delirium. Males have a higher risk of being diagnosed with ICU delirium (63% vs 36%) and being initiated on AAP (44% vs 40%) compared to females [4, 5].

In this retrospective investigation, we hypothesized that male gender was more likely to be associated with hyperactive symptoms of ICU delirium, and that males were more likely to be discharged on AAP after an ICU stay. After obtaining approval from the Institutional Review Board, we performed a retrospective analysis on patients admitted to the adult ICUs at the Penn State Health Milton S. Hershey Medical Center between January 2012 and December 2014. Charts were reviewed for the following inclusion criteria: age older than 18 years and AAP initiation in the ICU. Patients were excluded if they were on AAP prior to ICU admission. Documentation was analyzed for symptoms associated with AAP initiation based on the previously described Intensive Care Delirium Checklist Worksheet (ICDSC), pre-existing psychiatric diagnoses, and ICU type. Analyses were performed using SAS (v. 9.4; SAS, NC, USA) and significance was set at p < 0.05.

Of 12,984 patients admitted between 2012 and 2014, 346 (2.6%) patients were newly initiated on an AAP during their ICU stay, and 32 (8.6%) patients expired prior to discharge. In total, 346 patients and 314 patients were analyzed for initial and discharge-related variables, respectively (Table 1). No gender differences were observed in the concurrent psychiatric diagnoses of major depression (p = 0.13), bipolar disorder (p = 0.54), or schizophrenia (p = 0.99). However, males had a higher length of ICU stay compared to females (p = 0.002) but not total hospital stay (p = 0.07). As previously observed, males had higher rates of initiation of AAP (p = 0.0001) and continuation after discharge (p = 0.034). We demonstrated that males were more likely to have documentation of agitation (p = 0.032), hallucinations (p = 0.018), impulsiveness (p = 0.033), and combativeness (p = 0.001) compared to females. No differences were found in documentation of restlessness (p = 0.251), confusion (p = 0.60), insomnia (p = 0.70), lethargy (p = 0.34), or depressed affect (p = 0.62).
Table 1

Demographics and clinical characteristics of ICU patients initiated on AAP for delirium (N = 346)

Characteristic

Male

(n = 230)

Female

(n = 116)

p value*

Age (years), mean (± SD)

60.1 (± 19.3)

58.4 (± 21.0)

0.459

Psychiatric diagnoses, n

 Major depression

82

51

0.133

 Bipolar depression

18

7

0.543

 Schizophrenia

6

3

0.990

Delirium manifestationsb

 Hyperactive symptoms, n

  Agitation

213

99

0.032*

  Hallucination

159

94

0.018*

  Combativeness

139

90

0.001*

  Impulsiveness

121

75

0.033*

  Restlessness

58

36

0.251

 Hypoactive symptoms, n

  Confusion

26

11

0.605

  Insomnia/altered sleep

169

83

0.704

  Lethargy

56

23

0.344

  Depressed affect

35

20

0.627

ICU subtype, n (%)

 Medical

53 (23)

36 (31)

0.201

 Surgicalc

177 (77)

80 (69)

 

Length of stay (days), median (IQR)

 ICU

11.0 (1–21)

8 (1–15)

0.002*

 Hospital

18 (0.25–35.75)

16 (0.75–31.25)

0.070

Discharge disposition, n (%)

 Home

37 (16)

37 (18.1)

0.548

 Expired

24 (10.4)

8 (6.8)

 

 Long-term care facility

163 (72.6)

86 (74.1)

 

Continuation of AAP on discharge, n (%)

123 (70.7)

51 (29.3)

0.034*

AAP atypical antipsychotic medications, ICU intensive care unit, IQR interquartile range, SD standard deviation

ap values from two-sample t test (mean), chi-square test (n), or Mann–Whitney test (median and interquartile range)

bp value from chi-square test, χ2 critical value = 3.841, df = 1, α = 0.05

cAggregated from neurosurgical, surgical, trauma, and cardiothoracic ICU populations. Medical implies all others

*Significant at p < 0.05

Prior studies have demonstrated higher rates of AAP initiation and continuation in male ICU patients. To our knowledge, our investigation is the first to show an association between male gender symptoms of hyperactive delirium and initiation of AAP in the ICU. As hyperactive symptoms are more visible and more likely to invoke safety concerns, we suspect that this leads to a higher rate of initiation and continuation of AAP in male patients. Thus, hyperactive symptoms drive the gender differences observed in AAP administration in the ICU. Further research is required to substantiate these findings and assess their clinical implications.

Abbreviations

AAP: 

Atypical antipsychotic medications

ICU: 

Intensive care unit

Declarations

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

KK, JMK, and ZJC designed the study, analyzed the data, and drafted and edited the manuscript. RSS and JP performed the chart review and edited the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

This study was approved by the Penn State College of Medicine IRB (STUDY00000628).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Authors’ Affiliations

(1)
Department of Anesthesiology & Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA
(2)
Department of Medicine, Section of Palliative Care, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA

References

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Copyright

© The Author(s). 2018

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