Original Contribution
Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial

https://doi.org/10.1016/j.jclinane.2017.02.007Get rights and content

Highlights

  • Postoperative cognitive dysfunction is commonly occurred in elderly.

  • Anesthesia impaired the cognitive function.

  • Propofol had little effect then inhaled anesthetics.

Abstract

Study objective

To compare the incidence of postoperative cognitive dysfunction (POCD) in elderly surgical patients (> 60 years) receiving different anesthetics (propofol, sevoflurane, or isoflurane) and to identify potential biomarkers of POCD in this patient population.

Design

Prospective, randomized, double-blind clinical trial.

Setting

University-affiliated teaching hospital.

Patients

One hundred and fifty elderly patients scheduled for laparoscopic cholecystectomy.

Interventions

Elderly patients undergoing laparoscopic cholecystectomy were randomly assigned to receive propofol, sevoflurane, or isoflurane anesthesia. Measurements: Cognitive function was assessed using neuropsychological tests at baseline (1 day before surgery [D0]), and on postoperative day 1 (D1) and day 3 (D3). Plasma S-100β and Aβ1–40 protein, IL-1β, IL-6 and TNF-α concentrations were assessed before induction of anesthesia (T0), after extubation (T1), and 1 h (T2) and 24 h (T3) postoperatively.

Main results

The incidence of POCD was significantly lower in the propofol group compared to the isoflurane group and the sevoflurane group at D1 and D3 (propofol vs. isoflurane: D1 and D3, P < 0.001; propofol vs. sevoflurane: D1, P = 0.012; D3, P = 0.013). The incidence of POCD was significantly lower in the sevoflurane group compared to the isoflurane group at D1 ( P = 0.041), but not at D3. Postoperatively, plasma S-100β and Aβ1–40 protein, IL-1β, IL-6, and TNF-α concentrations were significantly decreased in the propofol group compared to the isoflurane group.

Conclusions

Propofol anesthesia may be an option for elderly surgical patients.

Introduction

Postoperative cognitive dysfunction (POCD) affects 15–25% of surgical patients, the majority of whom are elderly. POCD causes substantial morbidity and mortality. Patients affected by POCD experience impairments in recent memory, concentration, language comprehension, and social integration [1]. Morbidity associated with POCD is most severe in patients > 60 years of age [2], [3]. The 5-year mortality rate due to POCD is estimated to be 70% [4]. POCD results in a substantial health care burden, including a prolonged length of hospital stay and increased health care costs [5].

The occurrence of POCD has been related to surgical trauma and general anesthetics [6], [7]. Surgical procedures may activate nuclear factor (NF)-κB and the release of cytokines, which impair the integrity of the blood–brain barrier. Anesthetics may have detrimental effects on cognitive function through the cholinergic system, including the nicotinic acetylcholine receptors M1 and M3, which play an important role in cognitive tasks, learning, and memory [7], [8], [9], [10].

Several studies suggest that intravenous and inhaled anesthetics are neuroprotective in cerebral injury [11], [12], [13], [14], [15], [16], [17]. Evidence indicating that anesthetic exposure impairs neurocognitive performance in older individuals is controversial [18], [19], [20], [21], [22], [23]. However, such information is necessary to guide clinical anesthesia, increase safety, and improve outcomes in elderly surgical patients. Propofol, isoflurane, and sevoflurane are commonly used in clinical anesthesia. In a previous report, Qiao and colleagues found that inhaled anesthetics aggravated POCD compared to propofol in elderly patients that underwent resection of esophageal carcinoma [24]. This study was based on patients undergoing long duration surgeries during which the target concentrations of propofol and sevoflurane were not constant. Furthermore, isoflurane was not included in the study, even though isoflurane is commonly used in the clinic. Currently, the comparative effect of propofol, isoflurane, and sevoflurane on postoperative cognitive function in elderly patients undergoing short duration surgeries is unknown. We hypothesized that propofol may provide better neurological and physiological outcomes than constant levels of inhaled anesthetics in this patient population. The objectives of this randomized clinical trial were to compare the incidence of POCD in elderly surgical patients receiving different anesthetics and to identify potential biomarkers of POCD in this patient population.

Section snippets

Study population

Patients scheduled for laparoscopic cholecystectomy between December 2010 and June 2011 were enrolled in this prospective, randomized, double-blind clinical trial (ChiCTR-OCC-11001411). Anesthesia on all patients was performed by one anesthesiologist, and a second anesthesiologist, who was blinded to the randomization, evaluated patients' cognitive scores and collected peripheral blood. A third anesthesiologist allocated included patients to 3 groups according to a computer-generated random

Patient characteristics

A total of 200 patients were eligible for inclusion in this study. Of these, 50 were excluded; 27 were excluded according to the exclusion criteria, and 23 declined to participate. A total of 150 patients (n = 50 patients in each group) participated in this study; data from all patients were included in the statistical analyses (Fig. 1). There were no significant differences in baseline demographic or clinical characteristics between groups (Table 1). There were no significant differences in

Discussion

This study showed that the incidence of POCD was significantly reduced on postoperative Day 1 and Day 3 in elderly patients undergoing laparoscopic cholecystectomy administered propofol compared to patients administered isoflurane or sevoflurane. The incidence of POCD was significantly reduced in patients administered sevoflurane compared to isoflurane on postoperative Day 1 but not on postoperative Day 3.

Numerous studies have shown that surgical trauma and general anesthetics have detrimental

Funding

None.

Conflicts of interest

None declared.

References (43)

  • M. Lundstrom et al.

    A multifactorial intervention program reduces the duration of delirium, length of hospitalization, and mortality in delirious patients

    J Am Geriatr Soc

    (2005)
  • N. Terrando et al.

    Resolving postoperative neuroinflammation and cognitive decline

    Ann Neurol

    (2011)
  • V. Fodale et al.

    Remifentanil and the brain

    Acta Anaesthesiol Scand

    (2008)
  • C. Adembri et al.

    Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism

    Anesthesiology

    (2006)
  • I. Lasarzik et al.

    Assessment of postischemic neurogenesis in rats with cerebral ischemia and propofol anesthesia

    Anesthesiology

    (2009)
  • Y.Y. Zheng et al.

    Propofol pretreatment attenuates aquaporin-4 over-expression and alleviates cerebral edema after transient focal brain ischemia reperfusion in rats

    Anesth Analg

    (2008)
  • N. Bedirli et al.

    Sevoflurane and isoflurane preconditioning provides neuroprotection by inhibition of apoptosis-related mRNA expression in a rat model of focal cerebral ischemia

    J Neurosurg Anesthesiol

    (2012)
  • R. Ye et al.

    Sevoflurane preconditioning improves mitochondrial function and long-term neurologic sequelae after transient cerebral ischemia: role of mitochondrial permeability transition

    Crit Care Med

    (2012)
  • Y. Liu et al.

    Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists

    Can J Anaesth = J Can Anesth

    (2006)
  • H. Sakai et al.

    Isoflurane provides long-term protection against focal cerebral ischemia in the rat

    Anesthesiology

    (2007)
  • X. Wang et al.

    Current clinical evidence on the effect of general anesthesia on neurodevelopment in children: an updated systematic review with meta-regression

    PLoS One

    (2014)
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