Controlling pain (Proceedings)

Pain is defined by the International Association for the Study of Pain (IASP) as:

An unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage. Controlling pain is a vital role for clinicians.

Types of Pain

Physiologic: High intensity fibers that act to protect by warning of contact w/ tissue damaging stimuli

Pathologic (clinical): Produced by peripheral tissue injury or damage to nervous system, and can be inflammatory (visceral/somatic) or neuropathic

Idiopathic: Pain that persists in absence of identifiable substrate

Definitions

Hyperalgesia is characterized by an increased response to a noxious stimulus, without a change in nociceptor threshold. This is illustrated by the slope of the line being greater than normal. Allodynia on the other hand is characterized by a decrease in the nociceptor threshold required to produce a response, (ie a non painful stimuli can induce a painful response).

Nociception is the process of detecting pain via pain receptors (nociceptors) and signaling noxious stimulus, it consists of transduction, transmission, modulation which leads to conscious perception of pain.

Transduction is the process that involves translation of noxious stimuli into electrical activity at sensory nerve endings. Nociceptors respond to thermal, mechanical, and chemical stimulation. Transmission is the process of sending the impulses throughout the sensory nervous system. Afferent signals from the periphery are relayed through the dorsal root ganglia to the dorsal horn of the spinal cord where sensory input can be modulated. Information then travels rostrally, finally reaching the cerebral cortex.

Modulation is the modification of nociceptive transmission. The body can regulate and modify incoming impulses at the dorsal horn.

Perception of pain can only occur in a conscious animal and is a result of the interaction of transduction, transmission, and modulation.

The concepts of peripheral and central sensitization explain a great deal about an animal's response to an injury and also pave the way for better pain management. Surgery produces inflammation and a change in sensitivity to noxious stimuli. As the local area of tissue injury becomes more sensitive, the threshold for subsequent stimuli decreases (termed hyperalgesia). The hypersensitivity is not localized just to the original site of injury; it spreads to other parts of the body, which is termed secondary hyperalgesia. When neurons in the dorsal horn are repeatedly stimulated, their rate of discharge dramatically increases with time, and this is central hypersensitization. The barrage of signals that arrive in the spinal cord causes changes in the dorsal horn neurons, which become "wound up." The neurons are hypersensitive even after the noxious stimulus stops. Specific receptors are involved in the process of "wind-up"; one is the N-methyl-D-aspartate (NMDA) receptor in the spinal cord. Ketamine is a noncompetitive NMDA antagonist, and this has resulted in numerous studies on ketamine's ability to prevent or treat pain, particularly when given prior to the painful insult.

Clinical Signs of Pain

Tachycardia, hypertension, dilated pupils, tachypnea, behavioral changes, vocalization, and abnormal posture/gait

Physiologic Consequences of Pain

Increased sympathetic tone, vasoconstriction, increased systemic vascular resistance, increased cardiac output, increased myocardial work, decreased gastro-intestinal tract tone, catabolic state, increased blood glucose, increased protein catabolism and lipolysis, and renal retention of H20 and Na with increased K excretion and decreased GFR. Coagulation abnormalities include increased blood viscosity, prolonged PT/PTT, fibrinolysis and platelet aggregation.

Treatment

Non-pharmacologic Treatment of Pain

Caring and supportive (environment clean and dry environment), visiting with family and familiar objects, and giving cats a place to hide. Direct drug therapy at the four steps in the nociceptive.

Options for therapy

Anesthetics, opiods, α2 agonists, benzodiazepines, phenothiazines, local anesthetics, NSAIDS, NMDA antagonists, TCA, anticonvulsants, corticosteroids.

Opioid Receptors

Mu: analgesia, respiratory depression, miosis, bradycardia, hypothermia and euphoria

Kappa: sedation, analgesia, and miosis

Delta: emotional response

Pure agonists: Morphine, hydromorphine, oxymorphine, fentanyl, methadone, codeine

Partial agonists: Buprenorphine (agonist and kappa antagonist)

Agonist-antagonist: Butorphanol (mu antagonist and kappa agonist)

Antagonist: Naloxone

Administration

All opioids should be administered by intravenous (IV) catheter whenever possible to insure distribution of the drug and to avoid the need for painful injections. The opioid pure agonists should be administered to effect. The partial opioid agonist buprenorphine binds avidly to m-opioid receptors and dissociates from these receptors relatively slowly, yielding a relatively long duration of action. Another clinical advantage is that it may be continued as an oral transmucosal medication when feline patients sufficiently recover to leave the critical- care environment. Transmucosal buprenorphine is readily absorbed from the oral mucosa in cats; it has proven useful at a dosage of 10–30 mcg/kg T.I.D.

Do not use NSAIDS in patients that are hypovolemic, GIT disease, renal disease, or platelet abnormalities. Agents that are more commonly used included carprofen, meloxicam, deracoxib, etodolac, and ketoprofen.

Sedatives used in the critically ill patient's include benzodiazepines, alpha 2 agonists, ketamine, and propofol. Benzodiazepines in normal healthy dogs/cats acts more like a stimulant than a sedative. However the use of this class of drugs in critically ill patients is recommended as it has good anxiolytic properties with minimal cardio vascular or respiratory depression. Examples include (Diazepam and Midazolam), with minimal cardiovascular side effects, mild respiratory depression, reduce cerebral oxygen requirement, and has a reversal agent (Flumazinil).

Alpha 2 Agonists, can have significant cardiovascular and respiratory effects. However, low doses may be used in conjunction with an opioid or benzodiazepine following stabilization. Examples would include medetomidine and xylazine.

Ketamine produces a catalepsy-like state, in which the patient feels dissociated from its environment, and marked analgesia. At low doses ketamine can enhance analgesia by preventing NMDA receptor mediated windup and subseqent sensitization of dorsal horn neurons. Use not recommended in seizure or head trauma patients.

Propofol is a non-barbiturate hypnotic with rapid induction/recovery. Anesthetic doses prevent perception of pain, while non anesthetic doses decrease analgesic requirements. Importantly, high doses cause significant cardiovascular and respiratory depression and propofol is not sufficient as a sole analgesic agent.

Selected pain control scenarios

Analgesia in Head Trauma

The patient with head trauma may need analgesics or anesthesia for many reasons, including surgical procedures, or control of soft tissue or orthopedic pain. The brain tissue itself is thought to be relatively pain-free, and care should be taken to try to complete a through neurological examination prior to administration of any analgesic that may influence this examination.

The brain requires a high oxygen requirement and thus the brain receives a large percentage of the cardiac output and cerebral blood flow is tightly regulated to prevent decreases in perfusion. A decrease in arteriolar pH caused by an increase in CO2 results in vasodilation, reduction in cerebral vascular resistance, and an increase in CBF (cerebral blood flow). In contrast hypocapnia results in intracranial vasoconstriction and a decrease in cerebral perfusion. Following TBI (traumatic brain injury), pressure autoregulation may be lost causing mildly decreased systemic blood pressures that otherwise might be considered safe to result in markedly reduced CBF. Recommendations may include, pre-anesthetic with an opioid or benzodiazepines, and induction with propofol or thiopental, and maintenance with increased ICP with propofol, barbiturate, or benzodiazepine, or with normal ICP(intracranial pressure) sevoflurane or isoflurane. No matter what decision is made, the important factor is to maintain adequate blood pressure to avoid worsening of brain injury.

Adverse effects of opioids such as respiratory depression and hypotension have greater significance in the presence of ICP elevation. Benzodiazepines are beneficial as they have minimal effects on respiratory or cardiovascular status, and they decrease the cerebral oxygen requirements. Propofol and thiopental both are known to lower ICP. Also, with both of these drugs adequate blood pressure needs to be maintained as they can cause significant hypotension which can further impact cerebral perfusion pressure. The inhalant anesthetics have dose related effects on ICP. A good protocol for anesthesia with head trauma would be premedication with a benzodiazepine and low dose pure opiod agonists (ex, Hydromorphone-it is reversible!), and induction and maintenance with propofol.

Analgesia in Pregnancy

Opioids are the analgesic of choice in pregnancy. NSAIDs not recommended, but a single dose can be given post C-section. Ketamine at low doses may be ok, but higher doses cause significant adverse effects (prolonged use can lead to low birth weight and birth deficits). Naloxone can be given sublingually if adverse effects after C-section when using opoids. A good protocol for C-section is propofol CRI and pure opiod agonist (morphine or hydromorphone) after the puppies/kittens are removed.

Analgesia in The Lactating Patient

NSAIDs can disrupt kidney maturation which is not complete until 3weeks of age, and NSAIDs do cross into breast milk. Opioids do cross into breast milk (in significant levels), while ketamine does not cross into breast milk. Thus, for lacating bitches that need analgesic, the following are recommended; pure opiod agonists (morphine is more hydrophilic, less likely to pass into milk). To prevent potential for drug side effects, avoid nursing during peak drug levels, and, where possible, time nursing immediately prior to the next dose and avoid sedatives with long half-lives.

Analgesia for Pediatric Patients

First 6 months of life - Neonatal 0-2 weeks, Infant 2-6 weeks, Weanling 6-12 weeks, Juvenile 3-6 months. Use opiods with lower doses for neonatal/infant compared to weanling/juvenile, and do not use with sedatives. Do not use NSAIDS in animals less than 8 weeks of age (inhibit maturation of the kidney in puppies or kittens).

In conclusion for the critical patient, it maybe best to use analgesic/sedatives that you are comfortable with, have reversal agents, and do not cause significant depressive effects on cardio-pulmonary systems. For analgesia, a mixed modality approach is often nice-(eg., soaker catheter, gabapentin, opoids, MLK and NSAID).

References

Armitage-Chan EA, Wetmore LA, Chan DL. Anesthetic Management of the Head Trauma Patient. JVECC 17(1) 2007, pp 5-14.

Mathews KA. Analgesia for the pregnant, lactating, and neonatal to pediatric dog and cat. JVECC 15(4) 2005, pp 273-284.

Mathews KA. Management of Pain. The Veterinary Clinics of North America. July 2000.