Effect of General Anesthesia Duration on Recovery of Secretion and Biochemical Properties of Tear Fluid in the Post-Anesthetic Period

DOI 10.1007/s10517-018-4145-3
Bulletin of Experimental Biology and Medicine, Vol. 165, No. 2, June, 2018
269
EXPERIMENTAL METHODS FOR CLINICAL PRACTICE
Effect of General Anesthesia Duration on Recovery
of Secretion and Biochemical Properties of Tear Fluid
in the Post-Anesthetic Period
E. Y. Zernii1, V. E. Baksheev1, E. I. Kabanova1,2, V. V. Tiulina1,2,
M. O. Golovastova1, O. S. Gancharova1, M. S. Savchenko1,
L. F. Sotikova2, A. A. Zamyatnin Jr1,3, P. P. Filippov1, and I. I. Senin1
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 165, No. 2, pp. 235-238, February, 2018
Original article submitted September 14, 2017
Changes in the biochemical composition of the tear film is a critical risk factor for the development of chronic perioperative dry eye syndrome, because increasing the duration of
general anesthesia did not affect the dynamics of tear secretion recovery, but slowed down
normalization of its structure and antioxidant activity in the post-anesthetic period.
Key Words: general anesthesia; dry eye syndrome; corneal erosion; antioxidant activity
of tears
Intensive development of modern medicine is accompanied by introduction of new surgical techniques;
their complexity and duration is steadily increasing.
In most cases, the existing standards for invasive procedures require general anesthesia. Despite relative
safety of short-term anesthesia, long period of general
anesthesia is associated with the risk of various complications [7]. Perioperative dry eye syndrome (PDES)
is the most common ophthalmologic complication of
general anesthesia (according to some estimates, up to
44% patients [6]). Primary PDES symptoms include
photophobia and foreign body sensation in the eye,
which disappear within 1-2 h of the postoperative period. However, in some cases, the disease can become
chronic (in up to 25% of patients [12]) and cause cor1
A. N. Belozersky Research Institute of Physico-Chemical Biology,
M. V. Lomonosov Moscow State University; 2K. I. Skryabin Moscow
State Academy of Veterinary Medicine and Biotechnology; 3Institute
of Molecular Medicine, I. M. Sechenov First Moscow State Medical
University of Ministry of Health of the Russian Federation, Moscow,
Russia. Address for correspondence: [email protected].
E. Yu. Zernii
neal lesions of various severity clinically classified as
erosions [8]. Due to uniquely high density of innervation of the cornea, the development of corneal lesion
is associated with severe pain syndrome. Moreover, in
severe cases, chronic PDES is accompanied by temporary or permanent visual function impairment, which
adversely affects patient’s quality of life.
PDES has complex etiology and its course can be
aggravated by age factors, genetic predisposition, concomitant diseases, corneal anomalies, etc. Impairment
of the pre-corneal tear film is the main pathogenetic
factor of PDES. This film consists of three structurally
and functionally different layers: the main aqueous
layer performs nutritive and protective functions, the
outer lipid layer regulates tear evaporation, and the inner mucinous layer provide its retention on the surface
of the corneal epithelium. Damage to one or more corneal layers associated with changes in the volume of the
secreted tear and/or its composition under conditions
of general anesthesia leads to insufficient cornea nutrition and protection from external factors [2]. Long-term
impairment of the tear film structure leads to chronic
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Bulletin of Experimental Biology and Medicine, Vol. 165, No. 2, June, 2018 EXPERIMENTAL METHODS TO CLINIC
destructive processes in the cornea, including oxidative
stress and local inflammatory responses, induction of
apoptosis and necrosis of corneal epitheliocytes, erosive
changes, and manifestations of PDES symptoms.
It is currently accepted that primary PDES is associated with a decrease in the volume and quality of
tear produced under conditions of general anesthesia.
On the one hand, the supressive effect of anesthetics
on parasympathetic innervation of the main lacrimal
glands significantly inhibits tear production. On the
other hand, general anesthesia affects also other tissues producing tear components, such as meibomian
gland and conjunctiva [10]. We have previously demonstrated that not only the volume of produced tears
decreased, but also protein composition (antioxidant
protection enzymes, inflammatory cytokines, etc.)
and, probably, lipid composition of the tear film are
changed under conditions of general anesthesia, which
can also induce pathological process in the cornea
[11]. The mechanisms of transformation of primary
PDES into the chronic form are poorly understood, but
it is known that the incidence of this form increases
with increasing anesthesia duration; therefore, the
risk of its development is associated with persistence
of secretory and biochemical disorders. At the same
time, it remains unclear, which of these factors has
the strongest impact on the development of chronic
corneal lesions.
The aim of this study was to specify the relationship between general anesthesia duration and tear production/tear recovery dynamics in the post-anesthetic
period, using the previously developed experimental
animal PDES model [10-12].
MATERIALS AND METHODS
The study was carried out on pigmented rabbits weighing 2.3-3 kg (KrolInfo). The animals were kept under
12/12 h dark/light cycle, at 22-25oC and 55-60% humidity. All procedures were performed in accordance
with the recommendations [9]. The study protocol was
approved by the bioethics commission of A. N. Belo­
zersky Research Institute of Physico-Chemical Biology (No. 1/2016).
The animals were divided into 4 groups (6 rabbits
per each) and subjected to general anesthesia lasting
0.5, 1, 3, or 6 h, produced by intramuscular injection
of 50 mg/ml tiletamine and 50 mg/ml zolazepam (1624 mg of the mixture per 1 kg body weight). When
required, the injections were repeated to maintain narcotic sleep for the required period.
Tear production intensity and tear film stability
were measured before and immediately after general
anesthesia, and also 3 and 6 h, and 1, 2, 5, 7 days
after anesthesia completion using Schirmer test [1]
and Norn probe [4]. Total antioxidant activity of the
tear was measured in samples, obtained by extracting Schirmer test strip fragments with 150 μl of PBS
using the hemoglobin-H2O2-luminol system [1]. The
chemiluminescence of samples was measured using
Glomax-Multi Detection System (Promega).
The data were processed statistically using SigmaPlot 11 (SYSTAT Software).
RESULTS
According to the results of the standardized Schirmer
test, a 3-fold decrease in the amount of secreted tear
fluid was observed in all animals under conditions of
general anesthesia (Fig. 1). However, normal tear production was restored as soon as in 6 h after recovery;
recovery rate did not depend on the duration of general
anesthesia. A different picture was observed, when tear
film stability was monitored (using the Norn probe) in
the post-anesthetic period (Fig. 2). Increasing narcosis duration increased the time required for complete
recovery of this parameter: from 6 h in cases of 30min and 60-min anesthesia to 1 and 2 days in cases
of 3- and 6-h general anesthesia, respectively. Thus,
increased duration of general anesthesia did not cause
long-term disturbances in tear secretion; its recovery
was primarily determined by the total recovery period
that lasted ~5 h. At the same time, protein and/or lipid
composition of the secreted tear was impaired during
anesthesia, as far as tear film structure was disturbed
and its recovery was slowed down, and both were
worsened upon anesthesia prolongation.
Changes in the biochemical composition of the
tear during general narcosis can affect not only proteins and lipids, but also other components, which
include the set of low-molecular-weight antioxidants
(cysteine, glutathione, tyrosine, uric and ascorbic acid
salts), which determine the overall antioxidant activity
Fig. 1. Dynamics of tear production recovery in animals subjected
to general anesthesia lasting for 0.5, 1, 3, or 6 h.
E. Y. Zernii, V. E. Baksheev, et al.
271
Fig. 2. Dynamics of tear film stability recovery in animals subjected
to general anesthesia lasting for 0.5, 1, 3, or 6 h.
Fig. 3. Dynamics of tear antioxidant activity in animals subjected to
general anesthesia lasting 0.5 h, 1, 3 or 6 h.
of the tear film [3,5]. Indeed, according to our data,
already in the course of anesthesia, there was observed
more than 2-fold decrease in the antioxidant activity of
tear in animals of all groups (Fig. 3). The time required
for recovery of this parameter increased by 5 days with
the increase in anesthesia duration from 0.5 h to 6 h.
Thus, the decrease in the content/acti­vity of biochemical tear components, such as proteins, lipids, and low
molecular weight antioxidants, is quite protracted after
anesthesia. As a consequence, there is no cornea epithelium protection from damage, including mechanical
factors, oxidative stress, infections, etc., for a long time.
It is the long-term decrease in the protective properties
of the tear film in post-anesthetic period, which can be
the main cause of PDES transformation into chronic
form, the probability of which, as shown previously,
increases with increasing anesthesia duration [8].
Thus, it can be concluded that general anesthesia
does not significantly affect the amount of secreted
tears, but reduces its protective properties; their recovery is delayed, taking up to several days depending
on anesthesia duration. These observations provide
grounds for specification of PDES prevention strategies in surgical patients, and suggest the advisability
of ophthalmic examinations of patients after prolonged
surgical interventions with respect to the risk of postoperative corneal lesions.
The study was supported by the Russian Science
Foundation (grant No. 16-15-00255).
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