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Pharmacokinetic and pharmacodynamics of intravenous dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery

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Abstract

Background

This study was designed to investigate the pharmacokinetics and pharmacodynamics of dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery.

Methods

Morbidly obese (body mass index ≥40 kg/m2) and normal weight patients scheduled for elective laparoscopic surgery were included (n = 8, each group). After baseline hemodynamic measurement, dexmedetomidine 1 μg/kg was administered over 10 min. General anesthesia was induced with propofol 1.5 mg/kg and fentanyl 4 μg/kg 20 min after completion of dexmedetomidine infusion; the lungs were mechanically ventilated after tracheal intubation. The pharmacokinetics of dexmedetomidine was analyzed by a noncompartment model. Hemodynamic data and peripheral oxygen saturation (SpO2) were measured up to 30 min after starting dexmedetomidine infusion. Sedation level was measured with the Observer’s Assessment of Alertness/Sedation (OAA/S) scale.

Results

Peak plasma concentration, area under the curve to infinity, elimination half-life, and apparent volume of distribution were significantly larger in morbidly obese than in normal weight patients (3.75 ± 0.56 vs. 2.54 ± 0.32 µg/l, P < 0.001; 2174 ± 335 vs. 1594 ± 251 ng h/l, P < 0.001; 225 ± 55 vs. 158 ± 53 min, P = 0.02; 310 ± 63 vs. 164 ± 41 l, P < 0.001, respectively). Although clearance was also higher in obese patients than in normal body weight patients (58.6 ± 10.7 vs. 44.9 ± 9.0 l/h, P = 0.02), it was lower in obese patients than in normal body weight patients after normalization to total body weight (0.47 ± 0.07 vs. 0.64 ± 0.09 l/h/kg, P < 0.001). There were no differences in systolic or diastolic blood pressure or heart rate between the two groups within the 30 min. Sedation level was deeper and SpO2 was lower in morbidly obese than in normal weight patients. More patients in the morbidly obese patient group experienced deeper sedation after the start of the dexmedetomidine infusion (P < 0.05).

Conclusion

The pharmacokinetics and pharmacodynamics of dexmedetomidine are significantly different in morbidly obese patients compared with normal weight patients. Level of sedation was significantly deeper, and oxygen saturation was significantly lower, in morbidly obese than in normal weight patients, probably resulting from higher plasma concentration after infusion of 1.0 µg/kg.

Clinical trial number, registry URL

ClinicalTrials.gov (NCT01864187), https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4.

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Author information

Author notes

  1. Bo Xu and Dongxu Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, China

    Bo Xu, Dongxu Zhou, Li Ren & Xingan Zhang

  2. Department of Anesthesiology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, 441021, China

    Dongxu Zhou

  3. Department of Anesthesiology, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, 519000, China

    Li Ren

  4. Department of Anesthesiology, Rutgers-NJMS, Newark, NJ, 07101, USA

    Steven Shulman & Ming Xiong

Authors
  1. Bo Xu
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  2. Dongxu Zhou
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  3. Li Ren
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  4. Steven Shulman
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  5. Xingan Zhang
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  6. Ming Xiong
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Contributions

BX participated in study design, data collection, and provided the critical revision. DZ participated in literature search, data collection, data analysis, data interpretation, and wrote the manuscript. SS participated in data analysis, data interpretation, and wrote the manuscript. LR carried out the data collection and analysis. XZ conceived the study and participated in its design and coordination. MX participated in study design, data analysis, and data interpretation. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Bo Xu or Ming Xiong.

Ethics declarations

Funding

Supported by the National Natural Science Foundation of China (Grant No. 61773130), the Special Project for Medical Science Development of PLA (Grant No. CGZ15C003), the Foundation for Sci & Tech Planning Project of Guangdong Province (Grant No. 2014A020215026).

Ethical approval

This manuscript describes human research.

IRB contact information: Guangzhou General Hospital of Guangzhou Military Command Medical Ethics Committee (Tel: +86-20-88653625, E-mail: gzjqzyy@163.com)

The study was registered before patient enrollment.

This report describes an observational clinical study.

The author states that the report includes every item in the STROBE checklist for case-control observational clinical studies.

This manuscript was not screened for plagiarism.

Informed consent

This study was conducted with written informed consent from the study subjects.

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Cite this article

Xu, B., Zhou, D., Ren, L. et al. Pharmacokinetic and pharmacodynamics of intravenous dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery. J Anesth 31, 813–820 (2017). https://doi.org/10.1007/s00540-017-2399-y

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  • DOI: https://doi.org/10.1007/s00540-017-2399-y

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