Page 47 - CASA Bulletin of Anesthesiology 2019 Vol 6 No 5

Vol.6, No.5, 2019

DOI: 10.31480/2330-4871/099
Endocrine system analgia, while males required only μ receptor stimula-
tion [49]. The same pattern was observed in supraspi-
Prolonged exposure to opioids affects glucose me-
tabolism on several levels. Some of these effects include nal analgesia where male rodents experienced greater
decreased production of insulin-like hormone type 2, analgesia from viscerosomatic pain than their female
counterparts during systemic and intraventricular, but
growth hormone, and cortisol [36]. This contrasts with not intrathecal, administration of opioid [50].
acute exposure to opioids, which stimulates the release
of growth hormone and insulin growth factor 1 [37]. Summarizing, chronic opioids have at least the the-
This is most likely secondary to release of preformed oretical potential to affect the outcome of the anesthe-
hormones. In contrast, chronic exposure leads to re- sia and surgery consider their potential to blunt stress
duced expression of mRNA, leading to depressed serum response, affect glucose metabolism, and cause sex-de-
levels. This depression of hormonal RNA was not uni- pendent pain responses.
versal, with some subjects having much more profound Cardiovascular system
effect than others [36,38]. Considering that interindi-
vidual variability in opioids metabolism has significant Data regarding the direct effect of opioids on the
clinical relevance, it is an interesting question if the dif- myocardium is limited [51]. Consequently, the clinical
ference in opioids metabolism has a real effect on glu- relevance of acute opioid administration on cardiovas-
cose metabolism. cular performance is likely minimal and mostly mediat-
ed via collateral vagal reflexes of histamine release [52].
The effect of chronic opioid intake to the urinary
free cortisol excretion demonstrated a significant de- Furthermore, studies investigating the direct effect of
pression in cortisol synthesize. However, such an effect chronic opioid intake are virtually non-existent. The
takes between one to twelve weeks of opioid intake consensus is that opioid receptors in the heart are not
to develop. Significant confounder here is the effect of involved in mechanical heart performance, but serve
co-existing chronic stress on the serum level of cortisol an important role in conditioning [47,49,50]. However,
and ACTH. However, it is sound to conclude that chron- most of the studies were conducted during acute expo-
ic opioids may blunt the stress cortisol response with sure of exogenous opioids to δ and κ opioid receptor
some theoretical significance during the delivery of [55,56]. The formation of heterodimers is one of the
anesthesia. This observation was reinforced by several most important mechanism of how opioid receptors
cases report [39]. Currently, opioid induced adrenal de- play in cardipotection. This effect is dampened by ß -ad-
2
ficiency is a recognized clinical phenomenon. Approxi- renergic receptor stimulation [56].
mately, 20% of chronic opioids user will experience its However, findings from bench research do not nec-
symptoms but most of them are related to fatigue and essarily translate into clinical observations. In retro-
poor emotional status [40,41]. These observations sug- spective study, Carman, et al. (2011) demonstrated
gest though that there is a risk of catastrophic adrenal an increased risk of myocardial infarction in a patient
crisis during anesthesia in chronic opioid intake. taking chronic opioids as compared to COX-2 [57]. The
Thyroid axis was mostly undisturbed, or poorly stud- excess risk was present despite adjustment for several
ied, in chronic opioids use despite their importance to confounders. The large study sample also strengthens
overall homeostasis [36]. Production of procalcitonin this retrospective observation. However, the authors
was unaltered as well as demonstrated in a single study were unable to conclusively attribute the increased
[42]. risk of acute coronary syndrome in chronic pain users
One of the best-established effects of chronic opi- [57]. More recently, a large retrospective study found
oids is its effect on sex hormones [43]. Opioids related that chronic opioid therapy was associated with an in-
sex hormones endocrinopathy emerges in more than creased risk of cardiovascular deaths, confirming prior
50% of women treated with chronic opioids leading to studies [6]. This was the second reason for increased
amenorrhea [36,44,45]. Hypogonadism concomitant to mortality among chronic narcotics users. Again, the in-
a depressed level of testosterone was also frequently herent limitations of a retrospective cohort study pre-
reported [43,44,46]. However, sex hormones interplay cluded the ability to address the underlying cause of
has rarely an influence on anesthetic plan. increased mortality in chronic opioid users.
Regarding sex-dependent differences in analgesia, However, what is interesting about these findings
hyperalgesia, tolerance, and dependence to opioids, are that they are contradictory to laboratory studies. In
the female sex has been woefully underrepresented vitro investigations and animals studies demonstrated
in studies [47,48]. However, there is a growing body of that opioids are able to condition myocardium to isch-
literature identifying such differences [48]. Differential emic events quite efficiently [58,59]. Therefore, the ex-
spinal analgesia was demonstrated in rodents where cess mortality secondary to the cardiac event cannot be
females required both μ and κ receptor stimulation for easily explained. It is possible that the reduced ability to

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