So, let’s start with the introduction.
Pain is thought and considered the fifth vital sign alongside body temperature, pulse rate, respiratory rate and blood pressure.
The recognition and management of pain in animals has gained considerable momentum over the past 3 decades.
Successful recognition and management of pain results in improved patients welfare, lower incidents of refectory pain and reduces morbidity and mortality in general.
However, pain recognition in veterinary patients remains a challenge as animals are unable to fully express what v they v are experiencing.
In humans experience of pain includes the intensity, location and duration which can’t be objectively quantified in animals.
However, the affective, motivational and cognitive components can only be at best extrapolated from the clinician’s or Owner’s point of view.
This is why in veterinary medicine we mainly base the presence of pain depending on physiologic indicators of deterioration.
It’s simple to understand why this will be challenging in the critically ill patients as these patients often will be on potent drugs which have side effects which can potentially mask these physiologic indicators of deterioration.
Let’s talk now about pain morbidity and why it’s important to treat acute and chronic pain too.
2- PAIN MORBIDITY
This is a table where you can see the different physiological side effects related to pain.
Left uncorrected the consequences of pain, as you can see, and distress may extend well beyond unnecessary suffering.
So here you can see the different side effects:
So we can see that tachicardia, hypertension to an increase of myocardial irritability, potential myocardial ischemia. We have also seen reduction in tidal volume and FRC, functional residual capacity, increased work of breathing, atelectasis, hypoventilation, hypoxaemia, impaired coughing as well, hypercoagulability, increased platelets adhesiveness, reduced fibrinolysis, leukocytosis and lymphopenia.
3- PAIN MORBIDITY
This is the second part of the last table.
So we have also assumed gastrointestinal side effects, endocrine and urinary.
You can see ileus, increased gastric secretion.
Also, in terms of endocrine effects a reduction of anabolic hormones such as instilling, testosterone or an increase of catabolic hormones, an increased lipolysis and some sodium balance, urinary detention which is quite uncomfortable in our patients.
So, it’s important to keep in mind these physiologic side effects purists by pain.
4- PAIN PHYSIOLOGY
The experience of acute pain is usually a consequence of the neurological process of nociception which is in turn produced usually by actual or potential tissue damage.
Nociception is often conceptualized as a horse step process.
They partially on the mechanism of traction or on the major classes of analgesic drugs available knowledge.
The therapy may be directed at any of the 4 major steps in the nociceptive pathway.
The steps are:
- Transduction at the periphery, so this is the conversion of pain stimulus into an electrical impulse by the nociceptors.
- Transmission through the neuronal axons ebbero the dorsal horn of the spinal cord or cordal nuclei.
- Modulation at the dorsal horn through the spinal cord perception at the cerebral cortex.
- Combination drug therapy that interferes with 2 or more of these steps is often more effective than monotherapy, only one drug.
This observation has given rise to the practice of multimodal analgesia which is the combination of two or more drugs that work at different levels or steps.
Several studies suggest that this strategy produces at least an additive analgesic effect.
Therefore by combining two or more agents in the same patient it may be possible to reduce the dosage of each of them which is a technique which may help to reduce the frequency and severity of side effects in critically ill patients.
5- PAIN PHYSIOLOGY
Drugs that are useful for treatment of acute pain and stress in critically ill patients include opioids, NSAIDs, local anaesthetics, alpha-2-antagonists and some sedatives and NSAIDs antagonists too.
There are no published reports of comparable and comparative studies of these treatments in seriously ill dogs or cats and most recommendations or human patients are empirical or extrapolated from studies in postoperative patients.
As you can see here, drugs can be used at different levels as we commented before and this is a nice example to show how multi modal analgesia may work.
6- PAIN PHYSIOLOGY
An important concept to understand pain is sensitization.
Sensitization is to find a decrease in the threshold and an increase in the magnitude of the response to noxious stimulation.
Responsiveness to previously known noxious stimuli and a spontaneous nociceptive signal transmission may both be developed due to sensitization.
We can find both peripheral and central sensitization, as you can see in this figure.
Both are deleterious for our patients.
The use of pre-emptive anaesthesia has been used to prevent the establishment of central and peripheral sensitization caused by incisional injury which covers only the period of surgery.
Pre-emptive analgesia is defined as the use of multimodal analgesia, as mentioned before, prior to painful stimuli or cures.
The aim is to avoid repeated afferent nociceptive impulses to induce neoplastic changes in neurons that lead to sensitization.
Quite often our critically ill patients undergo any surgical procedure as part of their treatment and the use of this technique may facilitate the further development of sensitization.
So I think this is something we all need to be aware of.
Finally we will talk about different options that we have available for the treatment of acute pain and stress in critically ill patients.
7- PHARMACOLOGIC CONSIDERATIONS
At the University of Liverpool we like to use these acronyms or this memo technique tool in order to remember or memorize the different options that we have available to treat acute pain.
It’s also useful in order to make a plan or an analgesic plan before an (elective) surgery.
So we use as an acronym NOPLAN that stands for NSAIDs, Opioids, Paracetamol, Local anaesthetics, Alpha-2 adrenoreceptors agonists, NMDA receptors antagonists.
8- PHARMACOLOGIC CONSIDERATIONS
We should never forget the nurse care of our patients or non pharmacological care for our patients.
So it’s important to keep our patients in on a dry and padded cage, lubricate their eyes as many analgesic drugs can reduce tear production, maintain an adequate temperature.
Make sure that they don’t get a full bladder which can cause discomfort and ensure oral care as well to avoid the formation of oral ulcers.
We are going to see each drug included in the NOPLAN to see when we can use them and the most important is when we shouldn’t be using them.
9- PHARMACOLOGIC CONSIDERATIONS-NSAIDs
The first group of drugs that we will be discussing are the NSAIDs, non-steroidal anti-inflammatory drugs.
As you all know they work by inhibiting the COX enzymes in the arachidonic cascade, therefore inhibiting the production of different prostaglandins.
Potential advantages of these drugs in critical care include their antipyretic and anti-inflammatory properties and the ability to continue patients on oral therapy once they have left their critical care environment.
NSAIDs also reduce opioid requirements after surgery or injury in humans by 30% and in combination with opioids are an excellent option for multi modal analgesia.
Some contraindications or disadvantages include a potential gastrointestinal or renal injury, complications that are even more likely to happen in critically ill patients.
NSAIDs should be avoided in hypovolemic or dehydrated patients due to the potential to develop acute kidney injury, in patients with any coagulopathy, pregnant or lactating animals and of course if they have already been treated with corticosteroids or other NSAIDs.
10- PHARMACOLOGIC CONSIDERATIONS-NSAIDs
These are the doses available for dogs and cats of what I consider to my opinion the three most commonly used NSAIDs, Meloxicam, Carprofen and Robenacoxib.
Non selective agents such as Clonexine or Ketoprofen should be avoided in this patient’s population as the risk of GIE ulceration is relatively high.
And finally it’s important to remember that currently there are no reversal or antagonist drugs available for the NSAIDs.
11- PHARMACOLOGIC CONSIDERATIONS-Opioids
The next pharmacological consideration that we will be talking about are opioids.
The classification of opioids is based on a receptor subtype activation and the degree of activation.
Therefore we can classify opioids into four categories:
- Agonist or new receptor agonist;
- New receptor partial agonist;
- Agonist and New antagonist;
- Antagonist, as you can see in the table.
Here you have different examples to the different categories.
12- PHARMACOLOGIC CONSIDERATIONS-Opioids
Opioids obviously have different side effects so they can produce vomit or emesis, except Butorphanol and methadone.
The most important one is morphine.
Morphine produces vomit or emesis in a high percentage of animals.
It can produce miosis in dogs and surprisingly mydriasis in cats.
Two of these opioids can produce histamine release, pethidine and morphine.
So this is something important to avoid in patients with potential histamine release, such as mast cell tumor.
It produces moderate respiratory depression and moderate bradycardia as well. It can produce hypothermia in dogs and hyperthermia in cats.
Some contraindications are in ophthalmologic or neurologic patients due to the emesis and in consequence of intraocular or intracranial pressure.
As we mentioned before, mast cell tumor we should avoid the somministration of pethidine and morphine as well as allergic patients.
13- PHARMACOLOGIC CONSIDERATIONS-Paracetamol
Paracetamol is another pharmacological consideration that we can take into account when dealing with critically ill patients.
Although it is classified as NSAID, Paracetamol has weak non-inflammatory properties and doesn’t work on inhibiting cox enzymes.
It is also a weak inhibitor of prostaglandins synthesis.
Recently some proposed mechanism of action of paracetamol have been related to the vallinoid receptors which are responsible for the central and peripheral transmission of pain.
Some studies say that it can work also on some cannabinoid receptors, activating and extending the inhibitory serotonin pathways.
You can see the dosage here too.
14- PHARMACOLOGIC CONSIDERATIONS-Paracetamol
Side effects. The metabolism of Paracetamol relies on the level of glutathione through hepatic metabolism.
Some patients, such patients where their liver is not developed or not properly functioning, glutathione production is not enough and therefore there is an accumulation of toxic bioproduct of Paracetamol which is called NAPQI.
This bio product can cause severe damage to the liver: it’s important to remember that.
Finally, as you will probably know, Paracetamol in cats is absolutely contraindicated in any circumstances as it cannot undergo hepatic metabolism like dogs do.
15- PHARMACOLOGIC CONSIDERATIONS-Local anaesthetics
The fourth group of drugs are local anaesthetics.
We know that they work by blocking the sodium channels, they block the transduction and transmission of the noxious stimuli.
They are truly analgesic.
The rest of the drugs that we call analgesic shouldn’t be called analgesic but rather hypoalgesic as they reduce the pain sensation but they do not abolish, they do not stop noxious stimuli.
It’s simple, we call them analgesic but it’s important for you to remember that these aren’t truly analgesic.
It is also important to recognize the signs of toxicity when you use local anaesthetic drugs to allow prompt treatment.
There are more than these two but we will be focusing on CNS (central nervous system) toxicity and cardiovascular toxicity.
Central nervous system toxicity leads to different clinical signs as twitching and tremors, agitation, seizures and coma in some CNS cases.
The diverse defects of local anaesthetics are mediated on the heart and vascular system both directly and through the autonomic nervous system.
They decrease electrical excitability, conduction rate and force of contraction.
Arrhythmias can be different from tachycardia to bradycardia and ventricular fibrillation.
Local anaesthetics also have an effect on the systemic cardiovascular system leading to vasodilation and potential hypotension.
Rapid recognition of side effects and prompt treatment are key to successfully treat local anaesthetic toxicity.
16- PHARMACOLOGIC CONSIDERATIONS-Local anaesthetics
This is a table showing you the three most commonly used local anaesthetics like lidocaine, bupivacaine, ropivacaine.
You have the dose, the onset which is very important when using local anaesthetics, the duration and the toxic dose or the dose c that we shouldn’t be given.
17- PHARMACOLOGIC CONSIDERATIONS-Local anaesthetics
We can administer local anaesthetics through different routes.
Local as intranerves is the most common but do not forget that we have the option of intravenous regional anaesthesia as well for patients undergoing for example distal limb procedures.
This is a bit different in critically ill patients.
But we can definitely deliver or administer local anaesthetics in the epidural space before surgery or before recovery.
We also have the topical route using patches or administration using splash technique or infiltration in subcutaneous space.
Lastly we have the intravenous (IV) infusion.
This is probably the route most commonly used in ICU for critical patients when using local anaesthetics.
We have to remember that local anaesthetics have other uses or we can buse local anaesthetics for other options other than anaesthesia.
Although the evidence for some of them are weak, they are used as antiarrhythmic as what they call scavenger of free radicals and in general anaesthesia we can use it as MAC sparing effect to try to reduce the amount of inhalation anaesthetic, as anti-inflammatory and to increase gut motility so as GI prokinetic.
18- PHARMACOLOGIC CONSIDERATIONS-Alpha2 agonists
Medetomidine and dexmedetomidine two alpha2 adrenalitic agonist drugs are commonly used or commonly administered to our companion animals in the UK.
They have different effects, they have anxyolitic effects and the mechanism of action by which they produce analgesia by interaction with the alpha2 adrenalitic receptors are at spinal level and with some opioids receptors.
They therefore work at the modulation level if you remember the nociception pathway. However, its analgesic effects are shirter than their sedative effects and that is why alpha2 agonists are commonly given or administered as infusion to try to maintain an adequate plasma concentration.
These are the doses recommended to produce analgesia and sedation in critically ill patients.
They are usually lower compared to those given in anaesthetic premedication in healthy patients.
19- PHARMACOLOGIC CONSIDERATIONS-Alpha2 agonists
But do not forget that Alpha2 agonist drugs have, as many other drugs, different side effects. So we have different cardiovascular side effects.
They are defined as biphasic side effects.
So we have first vasoconstriction or peripheral vasoconstriction which in turn produces a reflex brachicardia and a reduction of up to 50% – 60% of cardiac output.
Also it can produce nausea and vomiting, polyuria so careful if they are not able to move. If so, please use a urinary cathetery fashion.
They can increase the myometral contractility so be careful in pregnant animals, they can produce hyperglicemia and hypothermia, so be careful with patients with diabetes or patients with a potential insulinoma.
20- PHARMACOLOGIC CONSIDERATIONS-NMDA receptor antagonists
Finally the NMDA receptor antagonist or ketamine is the last drug we will be talking about.
The interest of ketamine is the observation that at low doses ketamine helps limit post injury facilitations at the spinal cord level by its action at the NMDA receptor.
These are the different doses recommended to provide analgesia so they are lower doses than 0.3mg per kg so they can produce, provide analgesia without central effects.
21- PHARMACOLOGIC CONSIDERATIONS-NMDA
Receptor antagonists ketamine has different side effects so we have highlighted the increase in the intracranial pressure.
It has a unique cardiovascular effect, unlike other intravenous anaesthetics, ketamine stimulates the cardiovascular system if the catecholamines reserves are preserved.
This can increase heart rate, arterial blood pressure and cardiac output. That cardiovascular stimulation leads to an increased myocardial and cerebral oxygen demand.
In healthy patients the oxygen supplied to the myocardium can increase through coronary vasodilation and increase cardiac output.
A compromised heart might not be able to produce such a response so we need to be careful with the use of ketamine especially if we are using ketamine in a long-term.
Ketamine is also associated with an increase in salivation, bronchodilation as well which in some conditions might be helpful but we need to be careful with the salivation.
Also it can produce hyperthermia.
22- TAKE-HOME MESSAGE
So as a take-home message, by the end of this webinar you should be able to recognize the different side effects produced by pain.
So pain morbidity in critically ill patients that could be useful to you in order to decide what you need at another analgesic drug or you can just reduce the amount of analgesic drugs that you are delivering to your patients.
You should be able to be confident with the pain pathway and central /peripheral sensitization.
Also we refreshed the knowledge of the different concepts in terms of multimodal analgesia and what is preventive analgesia.
Also we have refreshed or we have gone through the different pharmacological considerations.
Hopefully we will be doing anther more extensive webinar on pharmacological considerations for pre medication and analgesia
In anaesthetized dogs and cats.
PAIN MANAGEMENT PPT SIDES
DO YOU HAVE ANY QUESTIONS?
I really hope this webinar helped you to refresh your knowledge in pharmacological considerations, in pain morbidity in patients or critically ill patients.
From time to time we will be releasing more webinars which we believe will help you to deliver high standardised patient care.
Please drop us an email if you have any doubts, if you have any questions or if you would like us to go through a particular aspect in pain management in veterinary medicine. We will also appreciate your feedback.
Thank you very much for your attention. It’s been a pleasure!