Hypoxia during immobilization,
not a simple cause
https://vimeo.com/216824933
Leith Meyer
Associate Professor Pharmacology, Department of
Paraclinical Sciences, Faculty of Veterinary Science,
Onderstepoort, University of Pretoria and Honorary
Research Fellow, Brain Function Research Group,
School of Physiology, Faculty of Medicine, University of
the Witwatersrand. [email protected]
Introduction
Arguably, hypoxia is the leading cause of morbidity
and mortality during chemical immobilization of
wildlife. This hypoxia is thought to be primarily
associated with drug-induced respiratory depression
and mainly occurs when potent opioids are used. That
opioids cause respiratory depression is a well-known
phenomenon. However, the assumption that this
depression is the primary cause of hypoxia during
chemical immobilization may not be entirely correct.
Opioids do depress the respiratory system by
affecting neuronal function in the central and
peripheral nervous systems. Neuronal depression
in the brainstem respiratory centres results in a
decrease in respiratory rate and rhythm, and reduced
chemoreceptor response to hypercapnia. Peripheral
neuron depression in the aortic and carotid bodies
also depresses chemoreceptor responses to hypoxia,
hypercapnia and acidaemia. These neuronal effects
result in hypoventilation with uncompensated
hypercapnia, acidaemia and hypoxia. These effects
are described as classical opioid-induced respiratory
depression. This depression does cause significant
hypoxia, but it doesn’t completely account for the
hypoxia that occurs during chemical immobilization.
Opioids also compromise the respiratory system
through a number of other mechanisms. Included
in these mechanisms are an increase in airway
resistance, a decrease in chest and abdominal wall
compliance, pulmonary hypertension and hyper-
metabolism. This presentation will focus on these
mechanisms and discuss the significance of other
capture related effects and drugs which may also
compromise respiration and exacerbate hypoxia,
hypercapnia and acidaemia.
Background
Opioids cause respiratory depression when they are
used during general anaesthesia and analgesia, both
in man and other animals. This respiratory depression
may cause hypoxic damage to vital organs and leads
to an increase in morbidity and mortality. Opioid
drugs cause respiratory depression mainly through
their activation of opioid receptors that occur in
respiratory neurones (McCrimmon & Alheid 2003;
Shook et al. 1990). Different opioid drugs do not
cause equivalent respiratory depressive effects as
their effects on respiratory function are dependent on
which opioid receptors they activate.
The activation of mu(µ)-opioid receptors, in particular
µ2 receptors, causes respiratory depression (Haji et
al. 2000; Shook et al. 1990). There is also evidence
that activation of both delta (δ)- and kappa (κ)-opioid
receptors also causes some degree of respiratory
depression (Ballanyi et al. 1997; Bowdle 1988;
Lonergan et al. 2003; Takeda et al. 2001), but the main
depressant effects of opioids appear to result from
the activation of μ2-opioid receptors (Haji et al. 2000).
The activation of opioid receptors results in a number
of effects that cause respiratory depression. The
neurones in the pre-Bötzinger complex appear to be
the most sensitive to μ-opioid agonists and therefore
the most important of these effects is a disturbance
in respiratory rhythm (Lalley 2003; Pattinson 2008).
Opioids also disturb respiratory rhythm by activating
respiratory neurones in the pons and also reduce the
ability of the ventral respiratory group neurones to
react to the chemoreceptor response to hypercapnia
and hypoxia (Lalley 2008; McCrimmon & Alheid 2003;
Pattinson 2008; Santiago & Edelman 1985; Shook
et al. 1990). Opioids also depress the neurones that
regulate tidal volumes, and thus may decrease the
depth of breathing (Lalley 2003; Lalley 2008). They
2017
MAY
21