Can Valeriana officinalis root extract prevent early ...

Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebocontrolled trial Soghra Hassani, Abbas Alipour, Hadi Darvishi Khezri, Abolfazl Firouzian, Amir Emami Zeydi, Afshin Gholipour Baradari, et al. Psychopharmacology ISSN 0033-3158 Volume 232 Number 5 Psychopharmacology (2015) 232:843-850 DOI 10.1007/s00213-014-3716-x

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Author's personal copy Psychopharmacology (2015) 232:843–850 DOI 10.1007/s00213-014-3716-x

ORIGINAL INVESTIGATION

Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial Soghra Hassani & Abbas Alipour & Hadi Darvishi Khezri & Abolfazl Firouzian & Amir Emami Zeydi & Afshin Gholipour Baradari & Rahman Ghafari & Wali-allah Habibi & Homeyra Tahmasebi & Fatemeh Alipour & Pooneh Ebrahim Zadeh

Received: 25 December 2013 / Accepted: 8 August 2014 / Published online: 31 August 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract Rationale We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity. Objectives The aim of this study was to evaluate the effect of Valeriana officinalis root extract on prevention of early postoperative cognitive dysfunction after on-pump CABG surgery. Methods In a randomized, double-blind, placebo-controlled trial, 61 patients, aged between 30 and 70 years, scheduled for elective CABG surgery using cardiopulmonary bypass (CPB), S. Hassani : H. Darvishi Khezri (*) : H. Tahmasebi Department of Nursing, Faculty of Medicine, Islamic Azad University, 7th km of Sea Road (Farah Abaad), Firoozkande, Sari, Iran e-mail: [email protected] A. Alipour Department of Epidemiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran A. Firouzian : A. Gholipour Baradari Department of Anesthesiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran A. Emami Zeydi Department of Nursing, Faculty of Nursing and Midwifery, Mazandaran University of Medical Sciences, Sari, Iran A. Emami Zeydi PhD Student in Nursing, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran R. Ghafari : W.0.99a 0.09 0.11 0.83 0.11 0.01 0.49 0.32 0.46 0.74 0.02 0.29 0.31

98 (98–99) 179 (170–192)

97 (97–99) 166.0 (159–180)

0.15 0.01

1 (1–2) 1 (3.2 %) 4 (12.9 %) AF VT VF

1 (1–2) 2 (6.7 %) 1 (3.3 %) 8 (25.8 %) 2 (6.5 %) 1 (3.2 %)

0.09 0.61a 0.35a 0.72 0.67a 0.29a

Lowest pO2 during operation (mmHg) Blood transfusion during operation Patients receiving prolong inotrope (>12 h) Patients requiring IABP Postoperative dysrhythmia

P value

9 (30 %) 3 (10 %) 3 (10 %)

Data are expressed as the median (inter-quartile range) or as number (percentages) BMI body mass index, HTN hypertension, COPD chronic obstructive pulmonary disease, LVEF left ventricular ejection fraction, MV mechanical ventilation, ICU intensive care unit, CPB cardiopulmonary bypass, NPT nasopharyngeal temperature, HB hemoglobin, MAP mean arterial pressure, SpO2 saturation of peripheral oxygen, pO2 partial pressure of oxygen, IABP intra-aortic balloon pump, AF atrial fibrillation, VT ventricular tachycardia, s ventricular fibrillation a

Fisher’s exact test

increasing the secretion of ACh and enhancing the choline acetyltransferase (ChAT) activity (Wang et al. 2014). Nam et al. investigated the effects of extract from valerian root in adult and aged mice. Study results indicate that valerian root extract (100 mg/kg) and valerenic acid enhance cognitive function, promote cell proliferation and neuroblast differentiation, and decrease serum corticosterone and lipid peroxidation in aged mice (Nam et al. 2013). Inflammation may be an important mechanism causing cognitive dysfunction (Gorelick 2010). Peng et al., in a meta-analysis, provided evidence that cognitive dysfunction is indeed associated with the concentrations of peripheral

inflammatory markers, especially interleukin-6 and S-100β (Peng et al. 2013). Considering that acute inflammation and decreased serotonin neurotransmitter resulting from abnormal tryptophan metabolism are the two mechanisms of developing cognitive dysfunction in these patients (Baumgartner 2007; FigueroaRamos et al. 2009), likely, valerenic acid contained in valerian through stimulating serotonin receptors and inhibiting of inflammatory factor NF-kB (Jacobo-Herrera et al. 2006; Patočka and Jakl 2010) result in decrease the incidence of cognitive dysfunction in patients, and this led us to assume that the prophylactic effect shown by valerian on cognitive

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Psychopharmacology (2015) 232:843–850

Table 2 MMSE score at baseline, 10 days, and 60 days follow-up in both groups Variable

Total MMSE score (0–30) Orientation (0–10) Registration (0–3) Attention and calculation (0–5) Recall (0–3) Language and praxis (0–9)

Time

F Statistic

Baseline (mean ± SD)

After operation 10th day (Mean ± SD)

After operation 60th day (mean ± SD)

Time

Group

Time* Group

Valerian Placebo Valerian Placebo Valerian Placebo

27.03±2.02 27.37±1.87 9.55±0.81 9.8±0.41 3±0 3±0

26.52±1.82 24±1.91 9.55±0.77 9.1±0.68 3±0 2.33±0.48

27.45±1.36 24.83±1.66 9.87±0.34 9.7±0.47 3±0 2.5±0.5

0.41

6.72b

42.28a

0.43

2.99c

7.41a

0.07

31.59a

21.82a

Valerian Placebo Valerian Placebo Valerian Placebo

4.48±0.77 4.33±0.88 2.52±0.67 2.57±0.57 7.42±1.2 7.63±1.03

4.13±1.18 3.73±0.94 2.68±0.48 2±0.45 7.16±1.04 6.8±1

4.42±0.76 3.8±0.96 2.71±0.46 2.03±0.49 7.42±1.03 6.8±0.92

1.76

1.39

2.36

2.95c

8.84a

22.15a

0.29

0.19

4.23b

*Interaction between time and group a

Significance level less than 0.01

b


c


dysfunction is most likely to result from anti-inflammatory actions and neuroprotective effects (Baumgartner 2007; Figueroa-Ramos et al. 2009; Wang et al. 2014). Although, more research is still needed in this regard. Sleep disruption is another potential risk factor for cognitive dysfunction in cardiac surgical patients (Sveinsson 1975). The relationship between sleep deprivation and cognitive dysfunction has been studied in a many studies (Fulda and Schulz 2001; Yildizeli et al. 2005). The available evidence indicates that valerian root might improve sleep quality without producing side effects (Bent et al. 2006; Taavoni et al. 2011). V. officinalis is effective in reducing insomnia associated with oxidative stress (Sudati et al. 2009). Therefore, other possible explanations for the effectiveness of valerian root extract in reducing postoperative cognitive dysfunction in our study may be that valerian through improvement of sleep quality leads to a reduction in cognitive dysfunction. The result of our study showed that the cognitive state of patients in the valerian group was better than in the placebo group at the 10 days after CABG; therefore, it seems that the use of V. officinalis root extract can prevent early postoperative cognitive dysfunction after on-pump CABG surgery. Moreover, since valerian has anticoronaryspastic, antihypertensive, and antibronchospastic (Circosta et al. 2007; Murti et al. 2011) properties, its application is reinforced in patients undergoing heart surgery.

This study, however, has some limitations. One limitation of the present study was that we only evaluate the patients’ cognitive function in the morning and did not evaluate it at the evening. Also, we only used MMSE as a subjective measurement of cognitive function and did not utilize several different screenings for diagnosis of cognitive dysfunctions, which indicates the need for further research. In addition, the study was not large enough to completely prove a benefit from valerian for cognitive dysfunction prophylaxis after CABG. In conclusion, the present study provides evidence for V. officinalis root extract as a prophylactic strategy in the prevention of cognitive dysfunction after CABG surgery. However, further robust randomized, blinded studies with large sample sizes are required in this field. Acknowledgments The authors wish to thank the staff of Mazandaran Heart Center, Mazandaran, Sari, Iran, and the patients at the Fatemeh Zahra Hospital, Division of Cardiac Surgery, and ICU Open Heart for their kind and efficient collaboration. The financial support of Research Deputy of Islamic Azad University is gratefully acknowledged. We are grateful to Dr. Farzaneh Tabassomi for doing neurocognitive test. Conflict of interest All authors declare no conflicts of interest; no conflict of interest exists for any of the authors associated with the manuscript and there was no source of extra institutional commercial funding, and the entire study was performed without external funding. The funding organization had no role in the design and conduct of the study, and in the collection, analysis, and interpretation of the data.

Author's personal copy Psychopharmacology (2015) 232:843–850

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