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NEUROLEPTANALGESIA
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- Neuroleptanalgesic anesthesia or neuroleptanalgesia (from the Greek, neurolepsis - seizure and analgos - without pain), is a state of sedated consciousness, induced for a medical procedure by a combination of opioids for pain control, and neuroleptics (also known as anti-psychotics) for sedation.
- Neuroleptanalgesia is produced by a combination of an opioid analgesic such as fentanyl, and a neuroleptic like droperidol or haloperidol. After administering nitrous oxide with oxygen, neuroleptanalgesia can be converted to neuroleptanesthesia, or complete sedation of consciousness.
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PHENOTHIAZINE
DERIVATIVES
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Phenothiazine derivatives
- Phenothiazine derivatives are basically three ring structures in which two benzene rings are linked by a sulphur and nitrogen atom.
- They act on the central nervous system by depressing the brain stem and connections of the cerebral cortex.
- These agents are weak anticholinergics and have extrapyramidal stimulating properties.
- In anatomy, the extrapyramidal system is a neural network that is part of the motor system that causes involuntary reflexes and movement.
- Extrapyramidal tracts are chiefly found in the reticular formation of the pons and medulla, and target neurons in the spinal cord involved in reflexes, locomotion, complex movements, and postural control.
- The agents acepromazine, triflupromazine and chlorpromazine are commonly used phenothiazines in veterinary anaesthesia.Clinical properties and uses
- Produce sedation, general calming and reduction in motor activity
- Antagonize dopamine excitatory chemoceptors and suppress vomiting.
- At high doses and some times in clinical doses induce extrapyramidal signs such as rigidity, tremors and catalepsy.
- Pulmonary functions are maintained following the administration of phenothiazines except slight depression in respiratory rate
- Induce urine production due to the suppression of antidiuretic hormone
- Animals undergoing intradermal allergic tests should not be administered with phenothiazines as they are potent antihistaninics
- Depletes catecholamines of the thermoregulatory center and render the animal’s body temperature susceptible to the changes in the environmental temperature.
- Tranquilization with phenothiazines is contraindicated in animals undergoing epidural, spinal or segmental anaesthesia as there is generalized vasodilation induced by phenothiazines.
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· Acupuncture (AP) is a complementary method of inducing
pain control during surgical procedures.
· It is a pain inhibition phenomenon caused by
stimulation of peripheral nerves via certain AP points.
· The degree of pain inhibition may be complete or
partial.
· Consciousness is
retained throughout the operation but many animals become slightly drowsy (as
if slightly sedated) during and for a short time after AA stimulation. All
other sensations (touch, traction, pressure, tickle etc) and reflexes (to
sight or sound stimuli, fear, traction etc) are intact.
· AA can be
induced by simple AP (manual twirling of the needles) but it is more
common to use electrical stimulation (ES) via the needles. In this
case the technique is called Electro-AP analgesia (EAA).
· Stimuli via the AA points are carried in the peripheral
sensory nerves to the spinal cord. They reach the midbrain via the ascending
spino-thalamic tracts. In the midbrain the ascending signals cause release of
endorphin, serotonin and other neurotransmitters which activate a
"descending inhibition mechanism" and prevent the "pain signals"
from the surgical area from reaching the cerebral cortex. Thus, AA can be
said to "close" various "pain gates" in the nervous
system. These gates are thought to be located in the spinal cord, thalamus
and possibly other areas. The result is that the human (and, presumably, the
animal) patient can feel the knife, the touch and traction etc but does not
"feel pain".
· Transcutaneous
Electro-Stimulation Analgesia (TESA) has been used in childbirth in the human
female and is somewhat comparable to EAA. Dorsal Column Stimulation (DCS) of
the spinal cord has been used in intractable pain in humans. ES via
electrodes implanted in specific sites in human or animal brain can induce a
high degree of analgesia, usually involving the entire body. Direct ES of human
thalamic or spinal areas can abolish clinical pain. Vaginal stimulation
(electrical or mechanical) can cause potent whole-body analgesia in rats.
o
· In all animals, during administration of the current,
the breathing movements appeared to be somewhat impaired. The body
temperature, the plasma cortisol level, and the pulse rate were raised during
the current administration. Moreover, the pulse rate was irregular.
· The electrocardiogram recordings showed pronounced
changes in cardiac activity.
· The results suggest that the apparatus did not cause
electroanaesthesia or electrosleep but had mainly an electroimmobilising
effect on the experimental animals. Because of the dubious effects on the
animals' welfare, the use of such an apparatus cannot be recommended.
· Hypothermia may develop in animals anesthetized in a
cool environment. A decrease in temperature of 1-3ºC below normal has been
demonstrated to provide substantial protection against cerebral ischemia and
hypoxaemia in anaesthetized dogs. Life threatening cardiovascular depression
may develop when the temperature decreases below 32.8ºC.
· Rectal or esophageal temperature should be monitored at
regular intervals during inhalation anesthesia , during protracted total
intravenous anesthesia and during recovery from anesthesia. Basically ,the
causes consists of a reduction in heat production by the animal , usually
coupled with an increased heat loss.
· It is very difficult to influence production of heat
but care should be taken not to wet the animal excessively to reduce
evaporative heat losses.
· Respiratory heat losses are increased when animal
breathes cold dry gas from non-rebreathing system.
· Fluids to be
administered i.v. should be warm.
The adverse effects of peri anaesthetic
hypothermia are
MUSCLE RELAXANTS
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INTRODUCTION
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Anaesthesia is
comprised of narcosis, analgesia and muscle relaxation.
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Muscle relaxation
is best achieved by the administration of neuromuscular blocking agents.
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To minimize the
dose of general anaesthetics
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To provide easy
access to the deep structures in the abdomen
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To aid in
intubation without laryngeal spasm
·
To help removal
of foreign bodies from the proximal portion of oesophagus as it is composed
of striated muscles.
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To aid in
reducing the luxated joints
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To ensure
immobility of the patient during delicate surgery
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To stabilize the
eyeball in central position during ophthalmic surgery
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PHYSIOLOGY OF NEUROMUSCULAR TRANSMISSION
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·
The large
myelinated nerve from the ventral horn of the spinal cord carries impulses to
the muscles. It carries stimuli to several muscle fibres that must be
activated for contraction.
·
As the nerve
approaches the muscle cell its branches lose their myelin sheaths and the
terminal ends lie on the surface of the muscle fibre. The nerve ending is
called neuromuscular junction.
·
The muscle fibre
membrane forms the groove and the grooves are deeply corrugated and called as
secondary clefts. The small gap between the nerve fibre terminal and the
muscle membrane is 60 nm wide and is called as junctional cleft. The areas of
secondary cleft are rich in mitochondria.
·
The action
potential travelling along the motor fibre produces depolarization of the
nerve terminal and triggers the release of acetylcholine, which crosses the
junctional cleft to stimulate nicotinic-receptors of the post synaptic muscle
membrane.
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Acetylcholine is
synthesized from choline and acetate in the presence of an enzyme acetyltransferase.
The acetylcholine molecules are present as uniform sized vesicles near the
presynaptic membrane and these areas are called as active zones.
·
When
acetylcholine is released it travels a minimum distance across the junctional
cleft to reach the receptors. Interaction between the receptor and
acetylcholine triggers an end plate potential, which is converted into muscle
action potential leading to contraction. After activating the receptor the
acetylcholine is rapidly hydrolysed to choline and acetate.
·
The drugs used
for neuromuscular blockade are classified into
·
depolarizing
muscle relaxants
·
nondepolarizing
muscle relaxants.
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DEPOLARIZING MUSCLE RELAXANTS
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- Depolarizing drugs produce initial muscle fasciculations and their action is rapid. Depolarized muscles are unresponsive to other stimuli such as electrical stimulation. Their action is not reversed by anticholinesterases. In partial paralysis neuromuscular monitoring slow depression of muscle twitch, no fade and no post titanic facilitation are noticed. The only drug used in this group is suxamethonium chloride (Succinyl choline). It is hydrolysed by cholinesterase and pseudocholineesterase into choline and succinic acid. Cholinesterase is synthesized in the liver. Hence liver damage, cachexia and malnutrition may prolong the action of suxamethonium. Organophosphorous compounds (use as ectoparasiti-cides) decrease the action of pseudocholinesterase, hence not recommended in patients recently exposed to such agents.
- Isoflurane, respiratory alkalosis, hypothermia and magnesium ions potentiate the effect of suxamethonium. Its effects are antagonized by halothane, acidosis and nondepolarizing drugs.
- Its administration is associated with the release of potassium into the blood from the muscles, which may result in cardiac irregularities. However prolonged administration results in decrease in serum potassium level.
- In dogs 0.3 mg/kg intravenously produces muscle relaxation and it extends upto 25 to 30 minutes. Repeat dose may result in dual block (nondepolarizing) which can be reversed with anticholinesterase drugs.
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NONDEPOALRIZING MUSCLE RELAXANTS
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- These drugs do not produce muscle fasciculations and are slow in action. Their effects can be reversed using anticholinesterase.
- The relaxed muscles will response to other stimuli such as electrical stimuli.
- During partial paralysis monitoring it shows fade and post titanic facilitation followed by exhaustion and depression of muscle twitch.
- Acidosis, magnesium slats and volatile anaesthetics potentiate the action of these agents.
- Nondepolarizing drugs are either quaternary ammonium or steroid compounds.
- The following are nondepolarising muscle relaxing agents
- Tubocurarine chloride
- Gallamine triethiodide
- Pancuronium bromide
- Vecuronium bromide
- Atracurium besylate
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TUBOCURARINE CHLORIDE
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- Tubocurarine is derived from Chondrodendron tomentosum tree. Not recommended in dogs due to its profound cardiac defects/effects.
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GALLAMINE TRIETHIODIDE
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- It has atropine like action on the heart.
- It also blocks the muscarinic effects of acetylcholine and acts directly on the B receptors resulting in tachycardia and rise in blood pressure which may lead to greater blood loss during surgery.
- This drug is excreted through kidney hence not indicated in patients with renal diseases.
- Dose - 1 mg/kg I.V, Duration: around 29 minutes.
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PANCURONIUM BROMIDE
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- It is an amino-steroid having no steroidal effects.
- Only 30% is metabolises and the rest is excreted unchanged through bile (10%) and the remaining through the kidney.
- It is contraindicated in patients having renal and hepatic diseases.
- It has minimal effects on cardiovascular system and some times produces rise in heart rate.
- Dose 0.06 mg/kg I.V, Duration around 31 minutes.
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VECURONIUM BROMIDE
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- It is a steroidal agent supplied in lyophilized form and soluble in water (stable for 24 hour only).
- Its duration of action is less than pancuronium.
- The drug is primarily excreted through bile in an unchanged form hence cannot be used in patients with hepatic diseases and recommended in patients with renal disorders.
- It has got minimal cardiovascular effects and does not release histamine.
- Dose 0.1 mg/kg I.V., Duration 18 to 25 minutes.
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ATRACURIUM BESYLATE
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- It is a novel muscle relaxant, which does not depend on body system to metabolize.
- It is broken down by a self-destruction process known as Hofmann elimination. It is a safer drug for cardiac and renal patients.
- It is administered with caution in patients with the history of anaphylaxis as it may release histamine.
- Dose: 0.5 mg/kg I.V, duration around 40 minutes further maintenance can be done with incremental dose (0.2 mg/kg) or by continuous infusion (0.5 mg/kg/hr).
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CISATRACURIUM BESYLATE
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- This drug is 5 times potent than atracurium, has no cardiovascular effects, does not release histamine, and is eliminated by Hofmann effects.
- No clinical literature is available on its use in veterinary anaesthesia.
- The other non depolarizing drugs are mivacurium, rocuronium and doxacurium.
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REVERSAL OF NEUROMUSCULAR BLOCKADE
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- Reversal of non depolarizing drugs is achieved by establishing high concentration of acetylcholine at the binding site.
- It is achieved by the administration of certain drugs, which will inhibit cholinesterase, and the drugs are pyridostigmine, edrophonium and neostigmine.
- In clinical condition reversal is attempted when at least two twitches are present.
- Atropine (0.04 mg/kg) or glycopyrrolate (0.01 mg/kg) administered intravenously atleast one minute prior to the administration of reversal agent to block the muscarinic effects of acetylcholine.
- Neostigmine 0.1 mg/kg I.V or Edrophonium 1.0 mg/kg I.V.
- Intermittent positive pressure is discontinued only after achieving train of four responses (all must be of equal force).
- The action of neuromuscular blocking agents are potentiated and prolonged by aminoglycoside antibiotics e.g. streptomycin, gentamicin, and tobramycin by decreasing the release of acetylcholine. Calcium can be given prophylactically in these patients. The other antibiotics include polypeptide antibiotics like tetracycline, lincomycin and metronidazole.
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VENTILATION
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- There following are the different types of ventilation
- Spontaneous ventilation
- Assisted ventilation
- Controlled ventilation
- Intermittent positive pressure ventilation
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TYPES OF VENTILATION
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Spontaneous ventilation
- It refers to breathing without any assistance from mechanical ventilator or the anaesthetist squeezing the rebreathing bag.
- Spontaneous ventilation can be abolished by hyperventilation.Assisted ventilation
- The patient initiates the respiration but the tidal volume is increased or assisted by the ventilator or by squeezing the rebreathing bag.Controlled ventilation
- The total breathing function of the patient is done entirely by a mechanical ventilator or by the squeezing of rebreathing bag.Intermittent positive pressure ventilation
- This is a technique used in controlled ventilation or assisted ventilation to force air into the lung during inspiration and lower it to atmospheric pressure or slightly below during expiration.
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USES
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- To provide ventilation during neuromuscular blockade and respiratory muscle paralysis due to toxins.
- To maintain near normal acid base status and oxygenation during long surgical procedures.
- To reduce ventilation-perfusion mismatch during prolonged periods of anaesthesia.
- To provide controlled respiration during thoracotomy. Intermittent positive pressure ventilation is essential to maintain pulmonary function in dogs, cats and in horses during open thorax as their mediastinum is incomplete. In cattle, sheep and goats the mediastinumis complete hence thoracotomy can be performed in one side with out the need of ventilator. But still use of intermittent positive pressure in these animals also helps in maintaining cardiopulmonary parameters.
- Used in patients whose respiratory centre is depressed by drugs, increased intracranial pressure, cerebral ischemia, and cardiac or respiratory arrest.
- Used in thoracic diseases, which affect the negative pressure of the thorax. (-5 cm of H2O during expiration and -12 cm of H2O during inspiration) eg. Diaphragmatic hernia, pleural effusion, pneumothorax.
- Used in patients having inadequate respiratory exchange due to obstruction or pulmonary oedema.
- Guidelines
- Volume, pressure, rate and inspiratory: expiratory ratio must be properly set in the ventilators.
- Volume
- Small animals 10 to 20 ml/kg
- Large animals 10 to 15 ml/kg (maximum limit is for open thorax)
- Pressure
- 15 to 30 cm of H20
- Rate per minute
- Dogs 8--- 14
- Cats 10---14
- Horses 6 --- 10
- Cow 6 --- 10
- Sheep & goats 8 --- 12
- Pigs 8 --- 12
- Inspiratory: Expiratory ratio
- It should be 1:2 or 1:3 to minimize the interference with venous return the inspiratory time is kept shorter than expiratory time.
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