Pre-medications & Sedatives

Pre-medications & Sedatives 

The choice of premedication will determine the characteristics of the anaesthetic, therefore when monitoring the anaesthesia during the maintenance phase, vital parameters should be considered in light of the premedication drugs administered.

Aims of Pre-medication 

To calm the patient prior to induction of anaesthesia. To reduce stress during induction of anaesthesia for both the patient and staff. To reduce the dose of anaesthetic drugs required for indiction and maintenance of anaesthesia. To contribute to a balanced anaesthesia technique. To provide analgesia. To counter adverse effects of other anaesthetic drugs.

Sedation 

This may be used instead of a general anaesthetic but normally at higher doses to gain the adequate amount of chemical restraint.  Sedation is not necessarily safer than a general anaesthetic due to less uproot of the cardiovascular and respiratory system, the airway in particular. Therefore, for the high risk patients opting for general anaesthetic may be safer, even if the procedure could be carried out with just sedation. In horses this is the opposite, where sedation combined with the local anaesthesia is more commonly used for significant surgical procedures, due to the high mortality risks of a general anaesthetic.

Routes of Administration 

Intravenous: rapid onset of action but requires restraint of the patient. Intramuscular: slower onset of action than the intravenous route but requires minimal restraint for injection. Site of injection does not appear to affect onset or depth of sedation. Subcutaneous: onset of sedation is slowest, but associated with least pain on injection.

Acepromazine (ACP)

ACP is phenothiazine, which act as antagonist to the dopamine receptors. They produce a calming effect, reducing anxiety and cause sedation which is most effective with an opioid. Available in tablet and injectable form. It requires 30 minutes after administration to take effect. Lasts for up to 6 hours, which can smooth recovery from anaesthetic. Can be given I.V, I.M or S.C.

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Effects of ACP

Cardiovascular - thought to be anti-arrhythmic properties, but it causes peripheral vasodilation, which may lead to reduction in blood pressure in hypotensive animals. This is why is should not be used in animals that are shocked or have cardiovascular disease. Respiratory - at high doses respiratory depression can develop. Thermoregulation - reduction. Nervous - it was thought that ACP lowered the seizure threshold, but there is little evidence to support this. Anit-emetic - with an opioid less likely to vomit.

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Contraindications of ACP

ACP will undergo hepatic metabolism and will be excreted in urine and bile. Dose rates should be reduced substantially (or the drug not used) in the following clinical scenarios: > Age: very old and very young > Renal disease > Hepatic disease > Hypovalaemia  > Congestive heart failure  > Brachycephalic breeds - especially boxers!

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Opioids

The opioid group of drugs is diverse and they vary with their duration and analgesic efficacy. Generally very safe and versatile group. Opioids can be classed by which opioid receptor bind to and according to whether they have agonist, partial agonist or antagonist effects. Opioid analgesics inhibit pain fibres in the dorsal root and can produce a feeling of euphoria. Commonly used opioid drugs include: morphine, methadone, pethidine, fentanyl, alfentanil, buprenorphine, butorphanol and naloxone.

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Pharmacological

Key element of perioperative control. Different intensities of analgesia can be obtained depending on the opioid used as a premed. The sedative effect of opioids is usually dose and drug dependent. Sedation from phenothiazines and alpha 2 antagonists is enhanced when they are combined with opioids.

Effects of Opioids on the Body

Opioids such as methadone, buprenorphine and morphine DO NOT cause clinically significant respiratory depression, but fentanyl and remifentanil given intravenously during anaesthesia are likely to cause respiratory depression. Negative effect on haemodynamics - can cause a reduction in heart rate. Most commonly seen when the drugs are given intravenously or in high doses. Morphine directly stimulates the vomiting centre, which often causes the sedated or pre-medicated animals to vomit shortly after administration. The effect is less apparent if morphine is used perioperatively for the management of pain.  Opioids stimulate the sphincters of the GI tract causing constipation but intestinal peristalsis tends to combat this effect.

Opioids and Pain Management

A full opioid agonist (morphine or methadone) should be given to animals that are likely to experience moderate to severe pain.  These drugs have relatively long duration of action and can be given repeatedly or by constant rate infusion if analgesia is of short duration or inadequate. Use of multimodal techniques may allow the dose of morphine or methadone to be reduced, or allow buprenorphine to be used instead.

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Contraindications of Opioids

Morphine cause vomiting when administered to animals that are not in pain. High doses of potent opioids may cause reduction in heart rate and respiratory depression.  Decreased peristalsis. Pupillary constriction.

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Alpha-2 Agonists

These act as profound sedatives and analgesics. They have a plateau effect where the level of sedation will not increase past a certain point, but the duration of sedation will increase. They are available in injectable form and can be administered I.M / I.V or S.C. They can also be easily absorbed via the mucous membranes. They can be combined with opioids and with ketamine for a more profound sedation. 

Medetomidine (1mg/ml) & Dexemedetomidine (0.5mg/ml)

These are the main alpha 2 adrenergic agonists used in small animal.

Summary of Product Characteristics

Dogs For restraint, sedation and analgesia associated with clinical examinations and procedures, minor surgery, pre-anaesthesia and as a premedication before thiopentone - halothane general anaesthesia and a premedicant before general anaesthesia with propofol.  In combination with butorphanol for sedation, analgesia and as a premedicant to thriopentane anaesthesia. 

Cats  For restraint and sedation. In combination with ketamine for induction of general anaesthesia prior to surgical procedures in the cat.  In combination with butorphanol and ketamine for general anaesthesia.  A a premedication before alphaxalone / alphadolone for general anaesthesia.

Effects of Alpha-2 Agonists

General - there is a significant drug-sparing effect. Induction agents should be given slowly to effect, as the uptake time is increased, inhalant anaesthetic levels will need to be reduced. Cardiovascular - a two phased effect on the cardiovascular system can be seen in initial vasoconstriction and an increase in blood pressure. This lasts for approximately 20 minutes until blood pressure is reduced below normal levels. Bradycardia and reduced cardiac output will be evident whilst the drug is active. Emesis - animals often vomit after administration. Thermoregulation - peripheral vasoconstriction reduces heat loss to patients  and are therefore less likely to become hypothermic. 

Contraindications of Alpha-2 Agonists

Care should be taken with the use of medetomidine in animals with cardiovascular disease or in poor general health. Should not be used with thiopentone or propofol in animals with cardia or respiratory disease. If renal or hepatic problems are present, the use of medetomidine with ketamine / medetomidine with propofol should be carefully assessed as they all need to be processed by the liver. Symptoms after absorption may involve clinical effects including dose-dependant sedation, respiratory depression, bradycardia, hypotension, a dry mouth and hyperglyceamia. Ventricular arrhythmias have also been reported. Respiratory and haemodynamic symptoms should be treated symptomatically.  Not recommended for use in pregnant animals. Dose rates should be reduced substantially (or the drug not used at all) for neonates, elderly patients, those with hepatic or renal disease, those in congestive heart failure, those with hypovoleamia and brachycephalic breeds.

Reversal - Atipamezole (Antisedan)

A reversing agent specifically conteracts the work of medetomidine and dexmedetomidine (although it can work for other alpha-2 agonists). in dogs, the same amount of atipam as medetomidine should be given, whereas in cats it is a half dose. This is commonly given I.M.

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Benzodiazepines

Act as anticonvulsants and anxiolytics. They produce limited sedation and no analgesia so are often combined with opioids as a premedication. They produce muscle relaxation and reduce skeletal muscle spasms.  Diazepam (5mg/ml) and midazolam (5mg/ml) are commonly used in veterinary anaesthesia. Midazolam is twice as potent as diazepam and shorter acting. At clinical doses benzodiazepines cause very few cardiovascular or respiratory effects. Injectable routes I.V, S.C or I.M - but diazepam is poorly absorbed by the I.M or S.C route and can cause pain on injection. Midazolam can be administered across the mucous membranes and intranasally and there is a preperation of diazepam which can be administered rectally. 

Benzodiazepines

Advantages Sedation enhanced by combination with an opioid. Good sedation in sick or young animals. Minimal effect on the cardiovascular system - useful in patients with cardiovascular disease. 

Disadvantages Sedation minimal in healthy animals - combination with an opioid required. Can cause excitement in healthy animals. Muscle relaxation may reduce ventilatory effort. Diazepam solubolized in propylene glycol causes pain on I.M injection and thrombophlebitis I.V - use medazolam if possible.