Herp Anesthesia & Analgesia Flashcards
1
Q
Describe the sedation of reptiles.
How does induction and recovery typically occur - what end gets sleepy first?
What are some common drugs used for sedation?
What are non-pharmacological methods of sedation used in reptiles?
A
MARMS – 48. Sedation
Maintaining Body Temp: POTZ
- Clearance time & AUC can be influenced significantly by body temp
Induction and Recovery
- Cranial to caudal- loss of withdrawl reflex & muscle tone (jaw tone last though)
- Recovery is caudal to cranial
- Deeper when lingual & palpebral reflex are absent
Benzodiazepines
- Anticonvulsant & hypnotic effects through enhancement of GABA
- Midazolam & Diazepam ; reversed with Flumazenil; watch for renarcotization
- High margin of safety
- Used alone or combo
Alpha-2 Adrenergic Agonist
- Great for minor procedures
- Initially produce hypertension, bradycardia and reduction in cardiac output
- Recommend supplemental oxygen
- Dexmedetomidine & medetomidine better than xylazine
Phenothiazines
- Acepromazine, antipsychotic drug
- Systemic hypotension
- Little information regarding its use in reptiles and not reversible
Opioids
- Usually need another drug…
- Chelonians show more of a profound effects
Sedation using low-dose anesthetic agents
Dissociatives
- Ketamine & Tiletamine
Propofol
- Short-acting, lipid soluble, sedative hypnotic
- Dose-dependent resp depression
Alfaxalone
- IM & IV
- Disadv: lack of proven analgesic properties, high expense, large volumes
Non-Pharm methods
- Vasovagal response
- Cold Narcosis
- Not an acceptable form or sedation for reptilians
2
Q
How does the temperature of a reptile affect its anesthesia?
How does it affect induciton, duration, and recovery?
A
- Thermoregulation and Environmental Temperature.
- Ectothermic – body temp directly dependent on environmental temp, assoc behaviors to modify that body temp.
- Absorption, distribution, metabolism, and excretion of drugs in reptiles is directly related to environmental temperature.
- Important to maintain patient within preferred optimal temperature zone (POTZ).
- Temperate and aquatic spp: 20-25 deg C (68-77F).
- Tropical spp: 25-35 deg C (77-95F).
- RES – induction, duration, recovery times after alfaxalone administration significantly shorter at hotter temperatures.
- Crocodiles administered medetomidine induced significantly faster at higher temps.
- Recovery times following atipamezole administration not different depending on temperature.
- Neotropical rattlesnakes, lower body temp did not have an effect following administration of ketamine, but recovery was significantly shorter at higher temp.
3
Q
Describe the anesthetic issues caused by the cardiovascular anatomy of reptiles.
What is the cardiac anatomy of reptiles like?
How does shunting affect anesthesia?
What is the hepatic first-pass effect?
How is IM injection in the hindlimbs versus IV injection in the tail different?
A
- Chelonians, lizards, snakes – 3 chambered heart, single ventricle and two atria.
- Atria are completely separate.
- Ventricle divided longitudinally into two chambers by incomplete IV septum.
- Allows mixing of oxygenated and deox blood and shunting from L to R and R to L.
- All reptiles have two aortic arches – right and left.
- Cardiac shunting can play a role in inhaled anesthetic uptake and elimination.
- Cardiac shunts may affect systemic blood pressure and arterial/venous oxygen concentration, in turn impacts anesthetic monitoring.
- Hepatic first-pass effect.
- May be more clinically important than renal portal system for PK.
- Venous blood flow from hind limb of chelonians, lizards, crocs drains into the ventral abdominal veins, either passes directly to the liver or indirectly via the hepatic portal vein.
- Any liver-metabolized or excreted drug administered in hind limb first enters liver before reaching systemic circulation, results in hepatic first-pass effect.
- Leads to lower bioavailability of drugs, lower plasma concentrations and/or reduced efficacy.
- Broad-snouted caimans administered ketamine and xylazine, no difference between forelimb and hind limb.
- Leopard geckos, estuarine crocs, ball pythons less effects in hind.
- It is advised to avoid administration of anesthetic drugs by injection in caudal body of reptiles.
- Caudal ventral tail (coccygeal) vein of lizards does not result in hepatic first effect, drains directly into the caudal vena cava.
- In turtles – some blood enters ventral abdominal vein, some enters caudal vena cava.
4
Q
Since reptiles lack a diaphram, how do they move air through their pulmonary systems?
Describe the respiratory anatomy of the four groups of reptiles.
How does low O2 and high CO2 drive respiration?
How does shunting affect gas exchange?
A
- Respiratory anatomy and physiology.
- All reptiles lack diaphragm.
- Force to move air during inspiration and expiration from movement of skeletal muscles.
- Chelonians – pelvic and pectoral muscles.
- Snakes – smooth muscle in lung walls and intercostal muscles.
- Lizards – lung smooth muscle, intercostal, pectoral, and abdominal muscles.
- Snakes – glottis is rostral, trachea has incomplete cartilaginous rings, bifurcates into two short bronchi at level of heart.
- Lungs elongated saclike structures, lined with resp epithelium.
- Most have a vestigial legt lung and functional right lung, ends distally as an airsac that is lined with nonrespiratory epithelium.
- Boid snakes have functional right and left lungs (left still smaller). Also caudal air sacs.
- Carnivorous lizards – glottis located more rostrally vs herbivores.
- Incomplete tracheal rings, bifurcation at heart base.
- Lungs of most lizards single-chambered, extend caudally into air sac.
- Some iguanids, varanids, chameleons have multichambered lungs that consist of an anterior and posterior chamber.
- Chelonians – glottis at base of fleshy tongue.
- Complete tracheal rings, short trachea, bifurcates into left and right intrapulmonary bronchus at thoracic inlet.
- Paired, multichambered, relatively rigid lungs.
- Crocs – glottis behind epiglottal (gular) flap.
- Lungs complex and multichambered, bronchi branch into multiple internal lobes.
- Reptiles have lower metabolic, cardiac, resp rates because of lower oxygen demands.
- Respiratory controlled by hypoxia, hypercapnia, and environmental temperature.
- Receptors increase ventilation during periods of low O2 and high CO2.
- Hypercapnia causes increased tidal volume, hypoxia increases respiratory rate.
- Stimulus to breathe comes from low oxygen concentrations.
- RR shown in tortoises to increase during hypercapnia and decrease during hypoxia.
- Higher demand for oxygen during increased temp or diving is met by increasing the tidal volume and not the respiratory rate.
- In O2 rich environment, reptiles decrease ventilation.
- Decreased RR and tidal volume.
- Intrapulmonary shunts (portion of pulmonary blood bypassing gas exchange) reduce efficiency of gas exchange in lungs and result in reduced arterial oxygen concentrations (PaO2).
- All reptiles lack diaphragm.
5
Q
Describe the preanesthetic evaluation of reptiles.
What are the five ASA physical statuses?
How can anesthetic fluids be administered in reptiles?
A
- Preanesthetic evaluation:
- Special attention to systemic disease (cardiovascular, respiratory) which may affect performance under GA.
- Fecal, hematology, chemistry recommended prior to anesthesia to determine health status.
- Imaging as indicated by history and PE.
- American Society of Anesthesiologists physical status classification:
- ASA 1 normal healthy
- ASA 2 mild, systemic dz
- ASA 3 severe, systemic dz
- ASA 4 severe systemic dz, constant threat to life
- ASA 5 moribund, not expected to survive without the operation
- Calculation of emergency drugs recommended.
- Supportive measures:
- Delay elective procedures until underweight, dehydrated, or debilitated animals have received tx to improve their condition.
- Dehydration and electrolyte imbalances should be corrected prior to anesthesia.
- Reptiles that fail to stabilize prior to surgery tend to succumb intraoperatively or postoperatively.
- IV or IO fluids, CRI.
- Percutaneously in jugular of chelonians, jugular, cephalic, ventral abdominal vein, or ventral tail veins of lizards, cranial vena cava or jugular vein of snakes.
- Lizards – tibia or femur common for IO.
- Percutaneously in jugular of chelonians, jugular, cephalic, ventral abdominal vein, or ventral tail veins of lizards, cranial vena cava or jugular vein of snakes.
6
Q
How does the preferred optimal temperature zone affect anesthesia?
What are the sites of IM administration for snakes, lizards, and chelonians?
What about IV administration?
What about IN adminstration?
A
- Injectable anesthetic agents:
- Prior to administration of any anesthetic or sedative drugs, reptiles should be maintained within their preferred optimal temperature zone (POTZ).
- Monitor core body temp during procedure.
- Avoid administration of high dosages of a single anesthetic agent.
- Consider protocols with multiple drugs combined with synergistic actions.
- Many drugs are readily reversible.
- For painful procedures, recommend an opioid in the premedication.
- Many protocols include alpha 2s, ketamine and/or midazolam.
- Morphine or hydro should be added if analgesia required in chelonians and lizards.
- Aquatic chelonians – protocols including dexmedetomidine/ketamine with or without opiate and local anesthesia are preferred to avoid use of gas anesthesia.
- Routes of parenteral drug administration:
- Snakes – epaxials. Cranial half of body.
- Lizards and chelonians – muscles of front limbs.
- SQ administration of anesthetic and analgesic drugs offers advantages and allows for capability of administering larger volumes, still acts rapidly.
- Lizards, IV caudal ventral tail vein.
- Tortoises and turtles (not sea turtles), jugular vein or brachial plexus.
- Subcarapacial sinus and dorsal coccygeal vein not recommended due to risk of accidental administration into intrathecal space, severe neurologic complications, permanent paralysis and death possible.
- Also, dorsal coccygeal vein not consistently developed in all spp.
- Subcarapacial sinus and dorsal coccygeal vein not recommended due to risk of accidental administration into intrathecal space, severe neurologic complications, permanent paralysis and death possible.
- Snakes, caudal ventral tail vein and jugular following cut-down.
- Intracardiac – cardiac tamponade after cardiocentesis in snakes has been reported, increased risk should be considered.
- Intranasal administration in chelonians – dexmed and ketamine only induced mild to moderate sedation; RES, difficulty administering the drugs intranasally due to defense behavior of the turtles.
- Once anesthetized, atipamezole intranasal shown to be effective.
- In large chelonians, large volumes are a limiting factor.
- Prior to administration of any anesthetic or sedative drugs, reptiles should be maintained within their preferred optimal temperature zone (POTZ).
7
Q
Describe the anesthetic drugs commonly used in reptile procedures.
Ketamine - what is its mechanism, what is it often combined with?
Telazol - when is it useful, when is it contraindicated?
Alpha 2s - what physiologic side effects are expected, what drugs are they commonly combined with?
Benzos - are they sufficient alone, what are they commonly combined with?
Propofol - when is it useful, what are some common side effects, what are some potential serious complications?
Alfaxalone - how does temperature affect the anesthesia, what is recovery like?
Inhalants - what is the MAC of green iguanas? How does shunting affect delivery?
A
- Drugs:
- Ketamine.
- Dissociative agent, dose-dependent.
- Alone – muscle relaxation inadequate, prolonged recovery.
- Combine with alpha 2 and/or benzo for reduction of dose.
- Tiletamine/zolazepam.
- Can be unpredictable, recovery may be prolonged.
- Contraindicated in dehydrated patients or those with underlying renal or metabolic disorders.
- Useful in large or dangerous spp when remote darting is required.
- Alpha 2 adrenergic agonists – medetomidine, dexmed.
- Sedation, muscle relaxation, analgesia in reptiles.
- Dose-dependent cardiovascular depression was documented.
- Combine with ketamine, safe in chelonians.
- Can also combine with benzos.
- Opioid can be added for analgesia.
- Concentrated formulations available.
- Benzodiazepines – midazolam and diazepam.
- Sedative and muscle-relaxant.
- Midazolam – water soluble, SC, IM, IV, more appropriate than diazepam which is not recommended for IM or SC injection.
- Used alone, anxiolytic, variable sedation but may be sufficient for minor procedures.
- Combined with ketamine and/or alpha 2, reduces all drug doses and attenuates the dose-dependent cardio depressant effects and prolonged recoveries commonly observed with ketamine.
- Midaz and alfaxalone SQ provides improved anesthesia in geckos vs alfaxalone alone.
- Reversible with flumazenil.
- Concentrated formulation available.
- Propofol.
- Short-acting, nonbarbiturate anesthetic
- IV or IO, short anesthesia (e-tube placement or abscess debridement).
- Or to allow for intubation for induction with inhalants.
- Respiratory depression, esp when administered rapidly.
- Complications assoc with accidental intrathecal injection include fore and hindlimb paralysis, coma, spinal necrosis.
- Sea turtles – respiratory arrest and death several hours post anesthesia.
- PF formulation should be discarded within 6 hours.
- New formulation containing 2% benzyl alcohol can be used up to 28d.
- Alfaxalone.
- Can administer IM or SQ.
- Rapid clearance.
- Metabolism independent of organ function.
- Pronounced temp dependent difference in anesthetic induction, plateau and recovery times reported.
- Associated with dose-dep cardiovascular and respiratory depression in mammals.
- Recovery is dose-dependent.
- Prolonged recovery with high doses.
- Major advantage over propofol is IM and SQ administration.
- SQ injection recommended for large volumes.
- Rapid induction times.
- Following initial use, any unused drug must be discarded after 6 hours and cannot be stored (USDA mandate).
- IV administration in iguanas and RES, rapid induction of light to surgical anesthesia, allowed endotracheal intubation.
- Increasing body temp greatly shortened recovery times in RES by 50%.
- Can combine with butorphanol, dexmed, midazolam.
- CV depression severe for tortoises combined with medetomidine.
- Geckos, combined with midazolam resulted in deep anesthesia.
- No clinically significant CV depression.
- Compared to dexmed and midazolam, alfaxalone and midazolam resulted in longer recovery times.
- Isoflurane, sevoflurane.
- Induction and maintenance of anesthesia.
- Variable results in some species.
- Intermittent PPV should be performed in all reptiles.
- Green iguanas – MAC iso 1.8%-2.1%, sevo 2.1%-4.1%.
- Sx plane iso 2-3%, sevo 3.5-4.5%.
- Both dose-dependent, depressive effect on cardiovascular system.
- Iso significantly reduces BP in green iguanas and ball pythons.
- Sevo resulted in faster induction and recovery.
- Due to R-L cardiac shunting in some spp, lung perfusion may be reduced.
- Concentrations of gas in lungs do not reflect concentrations in the blood or brain.
- Sudden changes in shunting can lead to sudden changes in inhalant anesthetic blood concentration, leads to significant changes in anesthetic depth.
- Slow induction, sudden arousal, inability to deepen, prolonged recovery.
- In lizards and snakes, changes in gas conc can be used to control anesthetic depth.
- In aquatic turtles and chelonians in general, change in gas will not lead to measurable changes in depth due to shunting, breath-holding ability, and VP mismatch.
- Ketamine.
8
Q
Describe the induction of anesthesia in reptiles.
Describe intubation of chelonians adn crocodilians.
When should cuffed tubes be used?
Describe the ventilation of reptiles during anesthesia.
What should EtCO2 be? What inspriatory pressure should be used? What are common rates?
What is the intraoperative fluid rate?
What heat support should be offered during a procedure?
A
- General Anesthesia:
- Induction with injectable or inhalants.
- Propofol, alfaxalone will be rapid.
- IM and SQ ketamine, midaz, alpha 2, alfaxalone, opioid combinations followed by maintenance with inahalational agent PRN.
- Induction times will be prolonged in species that can breath hold and inhalant agents may be ineffective.
- Chelonians – care should be taken not to intubate the left or right primary bronchus since tracheal bifurcation is cranial.
- Chelonians also have complete tracheal rings (lizards, snakes incomplete).
- Crocs – glottis behind epiglottal (gular) flap, has to be reflected ventrally to visualize glottis and allow for intubation.
- In large squamates, cuffed tubes can be used; otherwise uncuffed recommended.
- Maintenance.
- All reptiles require intermittent PPV.
- Maintain EtCO2 between 10 and 25 mmHg.
- Overventilation -> resp alkalosis, delays return to spontaneous ventilation during recovery.
- Can be performed manually or with ventilator.
- Any anesthetized reptile that is breathing spontaneously is light.
- Inspiratory pressure should not exceed 12 cm H2O.
- Anecdotally, 4-6 BPM recommended, adjust based on individual needs. Neotropical rattlesnakes, 1-2 BPM recommended.
- Intraoperative fluid therapy – 3 ml/kg/hr.
- Depth of anesthesia should be monitored regularly.
- Body temp has a profound effect on respiration, blood gases, and acid-base status in reptiles.
- Measure with esophageal or cloacal temp probes.
- Maintain in optimal temp range during anesthesia and recovery.
- Heat lamps, circulating water blankets, warm air blankets, etc.
- All reptiles require intermittent PPV.
- Induction with injectable or inhalants.
9
Q
Describe the monitoring of anesthetized reptiles.
How well does pulse oximetry work?
HOw is depth of anesthsia monitored?
How is HR monitored?
How is BP monitored? What are typical values?
How is hypotension managed?
A
- Monitoring Techniques:
- In green iguanas, oxygen saturation as measured by pulse ox underestimated saturation calculated by arterial blood gas analysis.
- Depth of anesthesia – presence or absence of reflexes such as head or limb withdrawal, righting reflex, palpebral and corneal reflexes, and toe/tail pinch/cloacal tone.
- However, significant anatomical differences.
- Corneal and palpebral reflex useful in many reptiles but cannot be assessed in snakes and geckos (except leopard) due to presence of spectacles and lack of eyelids.
- Righting reflex should be absent in snakes and lizards during sx plane of anesthesia, not useful in turtles and tortoises.
- Assessment of withdrawal of head and neck tone may be more useful.
- Snakes tend to lose muscle tone from the head to tail during induction and regain muscle tone from tail to head during recovery.
- Surgical plane of anesthesia – when no response to painful stimulus and no changes in cardiopulmonary parameters such as tachycardia, hypertension, or increase in respiratory rate.
- Cardiovascular monitoring.
- HR may be influenced by environmental temp, metabolism, noxious stimulation.
- MM color and CRT inaccurate in reptiles.
- Most accurate assessment of cardiac output in reptiles is heart rate.
- Esophageal, or doppler.
- Tachycardia and bradycardia can decrease cardiac output and reduce flow of blood to peripheral tissues.
- Baroreceptor reflex has been demonstrated in conscious green iguanas.
- US doppler flow devices most useful and reliable.
- Can be placed over the heart in snakes and lizards or over the carotid arteries in lizards and chelonians.
- Lizards – heart located between forelimbs (except in monitor lizards).
- Chelonians – side of the neck at coelomic inlet can be effective way to monitor cardiac function and measure HR.
- ECG.
- Limited references.
- P, QRS, T, some species have an SV wave before the P.
- Low electrical amplitudes may make interpretation challenging.
- Snakes – electrodes should be attached two heart lengths cranial and caudal to the heart.
- Larger spp – esophageal ECG can be placed.
- Persistent ECG and HR can also be detected in reptiles following CNS death, therefore ECG alone is of limited value.
- BP.
- Indirect has poor correlation with values from direct.
- Green iguanas had lower baseline ABP (MAP ~60-80) vs mammals.
- Reptiles maintained using inhalants are likely hypotensive.
- Increasing BP with dopamine and dobutamine has been shown to be ineffective.
- Norepi resulted in normotension in anesthetized iguanas (0.1-0.4 mcg/mL/min).
10
Q
What are some of the challenges associated with monitoring respiratory performance in reptiles under anesthesia?
A
- Respiratory performance.
- Mean baseline resp rate of healthy green iguanas ~25-50 BPM.
- Administeation of abx for confirmed infections, tracheal suctioning, and administer of O2 should be initiated prior to anesthesia PRN.
- Monitoring limited to pulse oximetry, venous blood gas analysis, and capnography.
- Pulse ox was validated in green iguanas.
- Skin thickness, pigmentation often reduces signal strength.
- High levels of methemoglobin have been reported for reptiles and affect pulse ox.
- Reflectance pulse oximeter probes are most useful and can be placed into the oral cavity, esophagus at level of carotid, or in cloaca.
- Study in green iguanas showed that O2 sat calculated by pulse ox was lower than SaO2 measured by ABG analysis. Baseline SaO2 > 90%.
- Manual ventilation or mech ventilation required under anesthesia.
- Blood gas analysis.
- Intracardiac shunting, ability to tolerate degrees of hypoxia, capability to convert to anaerobic metabolism makes it difficult.
- Intrapulmonary shunts will bypass gas exchange in the lungs.
- Circadian changes in arterial PO2 and SaO2 had values significantly lower in morning vs afternoon.
- Correct blood gas values for temperature.
- Capnography.
- R-L shunting make EtCO2 difficult to interpret.
- EtO2 appears to underestimate PaCO2 but is useful for trends.
11
Q
How should anesthetic emergencies in reptiles be addressed?
What is the drug of choice?
A
- Anesthetic Emergencies:
- Have emergency drug sheet ready.
- Airway, breathing, circulation.
- Monitor cardiac and circulatory function with ECG, doppler.
- Establish vascular access.
- Can give drugs in trachea.
- Doxapram respiratory stimulate IV or IO.
- May result in reduced CNS oxygen delivery and long-term brain damage if hypoxic.
- Not recommended for cerebral-pulmonary resuscitation.
- Epinephrine drug of choice for cardiac arrest.
- May result in reduced CNS oxygen delivery and long-term brain damage if hypoxic.
12
Q
Describe anesthetic recovery in reptiles.
Is room air or oxygen preferred for recovery?
How does isoflurane administration affect recovery? How can this be mitigated?
What other methods can be done to increase sympathomimetic tone?
When can the reptile safely be extubated?
A
- Recovery:
- DC inhalant and reverse injectables.
- Room air via Ambubag recommended for ventilation during recovery.
- Recent studies could not demonstrate any statistical or clinical significant difference in recovery times in monitors or bearded dragons with 100% O2 vs room air.
- Prolonged ax recoveries common.
- Iso in chelonians also assoc with slow recoveries due to hypotension, R-L shunting, reduced lung and tissue perfusion.
- Administration of epi in snapping turtles significantly reduced time to return of spontaneous breathing and complete recovery following isoflurane ax.
- An increase in adrenergic tone of the pulmonary vasculature leads to shunting of the blood away from the pulmonary circulation during episodes of apnea in turtles.
- By increasing the sympathomimetic tone of the systemic vasculature through administration of epi, pulmonary shunting is reduced, leading to accelerated recovery in turtles anesthetized with iso.
- Stimulation of the acupuncture point GV-26 also hastens snapping turtle recovery from isoflurane, comparable to administration of epi.
- Control POTZ.
- Assess respiratory status and continue assisted ventilation until patient is breathing spontaneously, has regained reflexes, and can be extubated.
- Extubate once spont breathing and jaw tone/tongue movement.
- CTM, may slip back into unconscious apnea.
- Extubate once spont breathing and jaw tone/tongue movement.
13
Q
What is the difference between pain and nociception?
What is required for a vertebrate to perceive painful stimulus?
What types of nerve fibers respond to noxious stimuli?
What portion of the brain in reptiles is analogous to the mammalian neocortex?
What types of opioid receptors are found within the reptilian brain?
A
- Reptile Nociception or Pain?
- “Pain” implies higher level cortical processing of information, therefore nociception and antinociception used when referring to pain and analgesia in most nonmammalian spp.
- Structurally and functionally, reptiles have the capacity to experience pain.
- Err on the side of reptile patient well-being and assume conditions are painful across all other vertebrate species.
- Neuroanatomic and Neurophysiological Evidence:
- All vertebrates have specialized sensory receptors, nociceptors, capable of detecting noxious stimuli (i.e. thermal, mechanical, chemical receptors) and afferent pathways relaying the information to the CNS.
- Efferent pathways initiate response, typically movement away from noxious stimuli.
-
For any vertebrate to perceive painful stimulus:
- Peripheral sensory receptor (i.e. nociceptor).
- Sensory pathway to spinal cord.
- Initial processing of painful stimulus within the spinal cord dorsal horn.
- Ascending pathways to brain.
- Processing of painful stimulus by brain.
- Descending pathways to control withdrawal, escape, or defensive/immobile responses.
- Reptiles have peripheral nociceptors, appropriate CNS structures and pathways, opioid receptors and endogenous opioids, reduction of nociceptive response with analgesics, pain avoidance learning, and suspension of normal behavior with pain.
- Nociceptors.
- Peripheral nociceptors have not been ID in reptiles specifically.
- Nobody has looked.
- Highly conserved across phyla.
- Identified in aquatic and terrestrial inverts, teleosts, amphibians, and birds.
- All nociceptors do not respond to same stimuli.
- Mechano vs chemical vs thermos or multimodal.
- Pit vipers – touch, thermosensitive nociceptive neurons ID in the trigeminal ganglia.
- Alligator – mechanonociceptors ID in the cutaneous plantar nerve.
- Peripheral nociceptors have not been ID in reptiles specifically.
- Ascending (afferent), Cerebral Cortical, and Descending (efferent) Pathways.
- Noxious sensory information is initially detected by cutaneous afferents, cell bodies in the dorsal root ganglia of SC, then separated into two main groups:
- Lage-diameter, myelinated A-fibers
- Small-diameter, unmyelinated C-fibers.
- Fihs, amphibians, reptiles, mammals have myelinated and unmyelinated afferent fibers sunning together in sensory nerves:
- Large, myelinated A fibers (AB)
- Small, myelinated A fibers (AD)
- Small, unmyelinated C fibers (C)
- Amphibians – small, slowly conducting fibers AB and C transmit majority of all impulses induced by noxious stimuli.
- Pit vibers, AB fibers shown to respond to noxious mechanical stimuli, AD fibers also but smaller somata.
- Sensory info detected by nociceptos, carried by cutaneous afferents, transmitted to dorsal horn of SC and continues to brain.
- Mammals – substance P peptide in small primary afferent nerves and SC expressed in direct assoc with painful stimuli
- Highly conserved across inverts and verts.
- In reptiles, substance P has been found in several turtles.
- Transmission of sensory info moves from S to brain.
- In mammals, pain-related activity detected by thalamus, spreads to insular cortex and anterior singulate cortex.
- Ascending tracts in the anterolateral quadrant of the SC that seems most likely to mediate pain are in the spinothalamic, spinoreticular, and spinomesencephalic tracts.
- Neurons project contralaterally.
- In reptiles, same basic ascending sensory pathways for visual, auditory, and somatosensory systems, involve fewer cell groups or subdivisions in the thalamus and pallium vs birds and mammals.
- Ascending tracts in the anterolateral quadrant of the SC that seems most likely to mediate pain are in the spinothalamic, spinoreticular, and spinomesencephalic tracts.
- In mammals, pain-related activity detected by thalamus, spreads to insular cortex and anterior singulate cortex.
- Telencephalon has two major subdivisions:
- Pallium, subpallium.
- Subpallium aka basal ganglia.
- Divided into striatum and pallidum.
- Contribute to septum and subpallial amygdala.
-
Neocortex of mammals homologous to the dorsal cortex of lizards/turtles.
- Present in all amniotes.
- Consists of the dorsal cortex and dorsal ventricular ridge, as well as olfactory, hippocampal, and pallial amygdala.
- Reptiles anterior dorsal ventricular ridge is a large intraventricular protrusion in the reptilian forebrain.
- Received info from sensory modalities and projects into the striatum.
- Function similar to mammalian isocortex, performing sensory integrations.
- ADVR in lizards has three longitudinal zones for visual, somatosensory, and acoustic info.
- Relayed by the thalamic nuclei.
- Posterior PDVR considered associative center that projects to the hypothalamus, comparable to the amygdaloid formation.
- Constitutes reptilian basolateral amygdala and may indicate an emotional brain.
- Descending motor pathways from hypothalamus and brainstem to the SC in the quadrupedal reptiles show similarities with mammals in cells of origin and spinal cord trajectory.
- Reptiles have interstitiospinal, vestibulospinal, and reticulospinal pathways.
- Crossed reticulospinal tracts regulate sensitivity of flexor responses.
- Crossed rubrospinal tract shown in turtles and lizards, not pythons.
- Small rubrospinal tract in a colubrid snake.
- Believed to be associated with limblessness.
- Crossed reticulospinal tracts regulate sensitivity of flexor responses.
- Overall, findings in reptiles suggest presence of functionally segregated thalamocortical projections is a conserved feature of brain organization among amniotes.
- Noxious sensory information is initially detected by cutaneous afferents, cell bodies in the dorsal root ganglia of SC, then separated into two main groups:
-
Opioid Receptors and Endogenous Opioids:
- Mu, delta, kappa in zebrafish, northern grass frog, rough-skinned newt.
- Aquatic turtles – mu and delta throughout brain, delta more abundant.
- Did not determine location and distribution in the SC.
- Kappa receptors not examined in the CNS.
- Endogenous opioid-related neurotransmitters:
- Proenkephalin derived peptides present in turtles.
- Brain of aquatic slider turtles, American alligators, anole lizards contains large quantities of endogenous enkephalins aka endorphins.
14
Q
How is pain measured and quantified in reptiles?
What methods are used in PD studies?
A
- Measurement and Quantification of Pain and Analgesia in Reptiles:
- Behavior changes.
- Noxious thermal stimulus.
- Thermal hind limb withdrawal latency.
- Noxious thermal stimulus applied to plantar surface of hind limb.
- Withdrawal latency automatically determined when the animal withdraws its limb or tail.
- Rapid application, does not cause long-lasting inflammation, instant latency quantification, unambiguous behavior after stimulus exposure.
- The animal can escape.
- Some argue this is not equivalent to pain.
- Some say reptiles are prone to thermal burns and less likely to respond to the thermal stimulus.
- The authors have seen 100% response rate to thermal stimulus.
- Physiological changes.
- HR increased in ball pythons following SQ capsaicin administration.
- Opioids did not alter that response.
- HR increased in ball pythons following SQ capsaicin administration.
15
Q
What types of opioid receptors are found in reptilian brains?
Does butorphanol provide analgesia in any species?
What about morphine or hydromorphone?
How much stronger is fentanyl than morphine? Did it provide analgesia in those studies?
Does buprenorphine work in reptiles?
What about tramadol?
What side effects are commonly seen with opioids in reptiles?
A
- Analgesic Drugs:
- Methods of administration.
- Historically, IM preferred.
- SQ also has advantages (minimal restraint and patient manipulation, larger volumes).
- Currently no published data showing IM is better than SQ in terms of analgesia.
- Meperidine (opioid used in humans) SQ in turtles caused measurable behavioral changes within 30 min.
- Transdermal patches have been used, plasma conc detectable.
- Fentanyl in ball pythons and corn snakes promising.
- Recuvyra topical solution (fentanyl) available for dogs and cats may be useful for reptiles.
- Oral administration – tramadol can be detected within hours of oral administration in loggerheads and thermal hind limb withdrawal latencies increased in RES within 4 hours.
- Opioids and opioidlike analgesics.
- Aopioids classified according to receptor subtypes – mu, kappa, delta.
- Also a fourth type of receptor (nociception or orphanin FQ receptor ORL).
- Two snake spp have endogenous brain opiates and RES have both proencephalin derived peptides and functional mu and delta receptors in the brain.
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Butorphanol was determined to have no analgesic efficacy in RES and beardies, corn snakes variable.
- Also no analgesic efficacy in green iguanas.
- Morphine was an effective analgesic in beardies and turtles.
- Hydromorphone appeared efficacious in RES for up to 24h.
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Fentanyl has 70-100xpotency of morphine.
- Can be administered transcutaneously or IV.
- Unclear if plasma concentrations had any biologic significance in skinks and ball pythons.
- Mean withdrawal from noxious thermal stimulus not statistically different with fentanyl patch in a recent ball python study.
- Decreases respiration rate in some snakes.
- Cannot definitively determine analgesic efficacy.
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Buprenorphine.
- Partial agonist activity at the mu recptor and partial or full activity at the delta receptor, antagonist activity at the kappa receptor.
- Significant hepatic first pass effect.
- Analgesic efficacy has not been demonstrated in reptiles.
- No analgesic efficacy in RES after thermal stimulus.
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Tramadol.
- Active metabolite O-desmethyl-tramadol (M1).
- Active metabolite has up to 200x greater affinity for mu receptors.
- Overall, tramadol binds mu with 6000 times less affinity than morphine.
- Potential for fewer side effects.
- Loggerhead turtles, concentrations of ramadol and metabolite remained above target conc for approx. 48h or 72h at 5 and 10 mg/kg.
- Behavior subjectively did not change.
- Sliders – PK trends similar with IM administration in forelimb and hind limb, but concentration of M1 was 20% higher in hind limb group.
- Resp depression in sliders approx. 50% less than morphine.
- Butorphanol and morphine cause profound resp depression in turtle, significantly less observed with tramadol.
- Active metabolite O-desmethyl-tramadol (M1).
- Tapendatol.
- Human drug, similar to tramadol.
- But only has weak serotonergic reuptake and without active metabolite.
- Shorter duration of antinociceptive efficacy vs tramadol.
- Resp depression not investigated, suspected to be less than other opioids based on human studies.
- Aopioids classified according to receptor subtypes – mu, kappa, delta.
- Methods of administration.
