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Acute pain is present in a patient because of pre-existing disease, the surgical procedure (with associated catheters,

drains, tubes, or complications), or a combination of disease-related and procedure-related sources.

Pain management should be a priority for the clinician, in terms of ethics, to ensure the animal welfare and in terms

of global medical management to reduce morbidity and mortality associated with inadequate pain management.

Lack of or inadequate pain management can lead to increased respiratory, cardio-vascular or gastro-intestinal

morbidity; increased length of stay in hospital and increased risk of developing chronic pain. Treating pain will

improve healing, decrease stress and anxiety related to hospitalisation and will provide a peaceful environment for

the animal and the nursing team.

The clinical signs of pain can sometimes be masked by the clinical signs of the underlying condition (shock, stupor,

comatose, etc.). However, the clinician must always consider that undergoing surgery, even a minor procedure, will

be painful. When a patient is hospitalized, the clinician must always consider that the animal might be in pain. Pain

must be assessed and reassessed constantly and treated adequately according to the level of pain.

INTRODUCTION

69

CRITICAL CARE

Non-pharmacological managementof pain

All measures aiming at the welfare and the comfort of the

patient must be set up: cosy blankets and pillows, heating or

ventilation, administration of water by syringe if the animal

cannot reach water easily, allowing time for rest without light

and noise, grooming for cats etc. The owners comfort and

cuddles is very important too.In the case of fractures, it is imperative to provide a proper

immobilisation of the limb with a bandage because the

manipulation of a fractured limb is extremely painful.

It goes without saying that taking X-rays of a broken bone is

not an emergency and must be done once the patient is stable

and can be sedated or even more often placed under general

anesthesia to get proper quality X-rays.

It is almost useless to give large amount of strong pain

medication before verifying that the patient is hospitalized in

good condition and receives tender loving care.

Pharmacological management of painThe concept of multimodal analgesia includes the

administration of two or more types of analgesics to prevent

or treat pain. This concept has shown that the administration of

various drugs can decrease the dose and thus the side effectsand sometimes, depending on the combination, the drugs

have a synergistic effect that provides more analgesia than the

expected cumulative effect. Opioids, NSAIDs, local anaesthetics,

ketamine and gabapentin showed a synergistic effect. Some

Acute pain management in the

peri-operative periodFranoise Roux DVM, PhD, DACVECC Alfort School of Veterinary Medicine 7 av. du General de Gaulle F-94704 Maisons-Alfort, cedex France. E-mail: froux@vet-alfort.fr

In case of fractures, it is imperative to provide a properimmobilization of the limb with a bandage (Photo F.Roux)

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Acute pain management in the peri-operative period - Franoise Roux

drugs have very low analgesic properties (ketamine, gabapentin)

themselves but have strong synergistic effects. Such products

are called co-analgesics.

The administration of pain medication must be accompanied by

a monitoring of pain and vital signs to ensure the administration

of an appropriate amount, neither too much nor too little.

Ideally, analgesics are administered in a continuous infusion

to avoid peaks and troughs of analgesic drugs delivery and

therefore pain.

The route of administration is also very important to consider;

for example the use of epidural morphine provides analgesia

comparable if not better than the intravenous route with

considerably lower dosages. Local analgesics can be used in

addition to general analgesics to decrease the dose of systemic

analgesics, thus decreasing side effects. The enteral route may

be used to relay the parenteral route as soon as the patients

condition allows. Due to first pass hepatic effect, opioids are

much less effective orally than systemically.

To avoid the emotional component of pain, e.g. related to the

fear of the treatment inflicted or stress of hospitalisation, the

use of low doses of tranquilizers (acepromazine, 0.02 - 0.05 mg

/ kg) may be beneficial.

A. Analgesic drugs used for peri-operative managementAs the perioperative, and especially the per-operative period,

is usually associated with severe pain, strong opioids are

recommended.

Fentanyl and Morphine

In countries like France, where oxymorphone and hydromorphone

are not available for pets, two potent opiods are used

intravenously: fentanyl and morphine. Those drugs are used in

human medicine and used off-label in animals.

Both drugs are and

pure agonists.Fentanyl has a very short half-life and is used preoperatively with

a syringe pump (see CRI in section B). Its onset of action is very

fast (several minutes).

Morphine can be used as single injections (0.1 0.5 mg/kg,

IM or IV) every 4 hours as its half-life is much longer. Its onset

of action is also several minutes depending of the route of

administration. As morphine may induce vomiting in the pre-

operative phase, especially if the patient is not in pain before

surgery (e.g. spay), morphine may be associated with a low dose

of acepromazine (0.05 mg/kg) for its anti-emetic properties. Sideeffects of pure-agonists are dose dependant and are vomiting,

bradypnea, bradycardia, myosis, dysphoria. The level of sedation

is also dose-dependant and is less marked with morphine than

fentanyl.

If a patient requires analgesia before surgery, it is advisable to

use pure agonists so that those drugs can be continued during

the per- and postoperative phase.

Both are considered as narcotics and must be kept in locked

cabinets.

Fentanyl Patches

Fentanyl patches are useful in the withdrawal phase of IVadministered opiods when the patient is considered able to go

home. The patch delivers a continuous dose of fentanyl through

the skin over a 48 to 72 hours period. The onset of action is 8

hours in cats and 12 hours in dogs, but often the concentration

plateau is reached in 12 hours in cats and 24 hours in dogs; it

is very variable from one patient to another. Thus, the Fentanyl

patch should be placed at least 12 hours before other painkillers

are withdrawn. The plasma concentrations and the efficacy are

highly variable from one animal to another. The patch must be

accompanied by a prescribed rescue pain medication in case

the animal seems painful at home.

Doses:

Dose range varies from 2 to 4 g/kg/h

Cat and dogs 40kg: combination of 2 patches

BuprenorphineBuprenorphine is also an opiod but as it is also a partial -agonist

it provides less analgesia but also less side effects. Once

buprenorphine is bounded to -receptors it is hard to displace,

thus it is not easy to use morphine after buprenorphine has been

given. Buprenorphine has a relative long half-life (about 6 hours)

but its onset of action is also relatively long (30-45 minutes).

Buprenorphine can be used in the postoperative setting once

the patient is not in as severe pain as during the immediate

postoperative phase. It is commonly used at 0.01 mg/kg IV

Q6h (range 0.005-0.2 mg/kg). It has a ceiling effect so it is not

helpful to increase the dose more than 0.02 mg/kg.

NSAIDs

Non-steroidal anti-inflammatory drugs should be used only in

a haemodynamically stable patient who is eating. They can be

part of the multimodal analgesia for surgery once the patient

Provide a peaceful environment for the animal and the nursing

team. (Photo F.Roux)

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EJCAP - Vol. 20 - Issue 1 April 2010

is stable and well hydrated, especially for orthopaedic surgery.

They are excellent pain medications in the late peri-operative

setting once the patient is ready to go home.

Gabapentin

Gabapentin was originally an anti-epileptic, which has recentlyshown its effectiveness in humans in addition to analgesics,

particularly in neuropathic pain. It is associated in humans with

a sharp decrease in consumption of morphine postoperatively.

Its way of analgesic action is still unknown; it acts on GABA

and NMDA receptors. This drug is only available in oral form.

Its bioavailability is 80% orally in dogs and its half-life is

3 hours. The peak plasma level is reached 2 hours after oral

administration. Even if this drug is only available as an oral form, it

can be administered 4 hours before surgery and postoperatively

dissolved in a small amount of liquid even if the animal is not yet

ready to be fed.

The dose currently used in dogs is 2-5 mg/kg orally 3 to 4 times

per day and 2.5-5.0 mg/kg 2 times per day in cats. It is easy to

open the capsules and to dissolve the powder in a small amount

of water to be given orally with a syringe. Elimination is via urine

so the dose should be reduced in case of renal impairment. The

cost is modest. Withdrawal should be gradual to avoid anxiety,

behaviour change or seizures.

B. Constant rate infusion (CRI)The intravenous constant infusion of a drug is used to maintain

an equal concentration of the drug in blood throughout its

administration. It is performed using infusion pumps or syringe-

pumps.

Most often it requires a loading dose. This loading dose can

be for example half the dose used for intermittent injection

depending on the half-life of the drug.

Fentanyl:

Fentanyl is a very potent opioid analgesic that provides significant

analgesia at doses of 0.3 to 0.7 g/kg/min after a loading dose

of 5 to 10g/kg. It can also be used at lower doses of about

0.15 g/kg/min after a bolus of 10 g/kg, thus sedation will

be reduced but so will analgesia. Fentanyl can be combined

with ketamine to reduce postoperative central and peripheral

sensitization of neurons.

Ketamine:

Used for many years as an anaesthetic, ketamine has recently

shown analgesic properties at low doses (0.1 - 1.0 mg/kg IV)

by antagonism of NMDA receptors. It potentiates the anti-

nociceptive effect of opioids and -2 agonists. As a co-analgesic,

its use reduces the doses of morphine needed for the same level

of analgesia. Although contra-indicated for anaesthesia in head

trauma patients, ketamine has shown anti-convulsive properties

at low doses and can be used as an analgesic in patients with

head trauma. Ketamine is used as constant rate infusion (0.6

mg/kg /h) and the dose must be reduced gradually.

Medetomidine and Dexmedetomidine

Low doses of medetomidine (1-2 mg/kg/h) or dexmedetomidine

(0.5 - 1 g/kg/h) have showed analgesic properties with very

few cardiovascular effects observed at anaesthetic doses. Their

analgesic effect is maximised by opioids. Some side effects of

the 2-agonists may remain, as bradycardia, increased left atrial

pressure and reduced oxygen delivery to tissues. Medetomidine

and Dexmedetomidine are not recommended, even at low

doses, in patients haemodynamically unstable or suffering from

heart disease.

The intravenous constant infusion of a drug is performed usinginfusion pumps or syringe-pump Photo (F.Roux)

Photo (F.Roux)

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Acute pain management in the peri-operative period - Franoise Roux

For pets that weigh more than 5kg, it is usually convenient to

pick a rate of 10ml/hour/dog regardless the size of the dog, thus

adjustment of 1ml/hour equals a 10% variation.

For example, take the case of a dog of 20kg, its maintenance

requirements are 50 ml/hour. The pain medication CRI can berun at 10ml/hour on a separate bag and the maintenance fluid

will be run at 40 ml/h on another line. A single intravenous

catheter is sufficient using a 3-way stopcock.

2) Choose a duration of administration

Usually, CRI bags are prepared for a 25 hour-period, which avoids

the preparation of several bags per day, and also saves time for

nurses and avoids waste if the protocol or the dose change the

next day. The reason why 25 hours is chosen is because the

bag volumes are a multiple of 25 (100ml, 250 ml, 500ml and

1000ml) and it gives 1 hour bonus time for the nurses to

change the bag before the patient runs out of pain medication.

So for an administration at 10 ml/h over 25 hours, you need a

250 ml bag of isotonic crystalloids (NaCl 0,9%) (25 h x 10 ml).

3) Choose the dose of drugs to be administered

For Example

Ketamine CRI at 0.6 mg/kg/h.

Lidocaine CRI at 50 g/kg/min.

4) Calculate the amount in mg for 25 hours and the volume

in ml based on the weight and the duration of administration

Ketamine CRI:

Ketamine at 0.6 mg/kg/h for a 20 kg dog over 25 hours:

Amount in mg: 0.6 mg x 20 kg x 25 h = 300 mg

Concentration of ketamine: 100 mg/ml

Volume in ml: 300/100 = 3 ml

Lidocaine CRI:

Lidocaine at 50 g/kg/min for a 20 kg dog over 25 hours:

Amount in mg: 0.05 mg x 20 kg x 60 min x 25 h = 1500 mg

Concentration of lidocaine: 20 mg/ml

Volume in ml: 1500/20 = 75 ml

5) Prepare and label the bag

If volumes are small (less than 5 ml), drug is added to the

crystalloid bag.

Lidocaine:

Lidocaine administered IV at anti-arrhythmic dosages provides

systemic analgesia, captures free radicals and increases

the gastro-intestinal motility. Administered during general

anaesthesia, doses of 50 g/kg/min of lidocaine can significantly

reduce the MAC of isoflurane required to abolish nociceptivestimuli. Lidocaine should be used with caution in the cat

intravenously and doses should be reduced to 0.2-0.5 mg/kg if

needed for anti-arrhythmic properties. Lidocaine CRIs are not

recommended in cats. The loading dose for analgesia in dogs is

usually 1 mg/kg followed by a 50 g/kg/min CRI.

DRUGS Concentration Loading Dose CRI dose

Fentanyl 50 g/ml 0.3 - 1 g/kg 2 - 4 g/kg/min

Morphine 10 mg/ml 0.05 - 0.2 mg/kg 0.02 - 0.1 mg/kg/h

Ketamine 100 mg/ml 0.5 - 1 0.3 - 0.6 mg/kg/h

Lidocaine 20 mg/ml 0.5 - 1 mg/kg 40 - 80 g/kg/min (DOGS only)

Medetomidine 1 mg/ml 1 - 2 g/kg 1 - 2 g/kg/h

Dexmedetomidine 0.5 mg/ml 0.5 - 1 g/kg 0.5 - 1 g/kg/h

Attention, some Drugs are listed per minute or per hour, others in g or mg.

How to prepare a CRI?

1) Choose an hourly volume

You must first choose the volume administered per hour,

regardless of the substance used.

It is convenient to prepare a bag dedicated to the pain

medication CRI independent of the daily fluid needed. Some

authors suggested adding the pain medications to the daily

fluid needs, it can be convenient but it is harder subsequently to

adjust the fluids based on the clinical status of the patient (e.g.:

hypovolemia, fluid overload, etc.)

Maintenance requirements are about 2 ml/kg/h for a cat and

2.5 ml/kg/h for a dog.

For cats, due to lower volumes needed as a maintenance rate,

it is sometimes worthwhile to prepare the CRI in maintenance

fluids, especially for low requirements (e.g. cardiac cat).

It is convenient to prepare a bag dedicated for painmedication(Photo F.Roux)

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pain. 0,1mg/kg/h is considered to be a high dose used in the

immediate postoperative period of very painful surgery.

It is advisable to wean CRI over at least one or two days.

With the 10ml/h rate, each 1ml/h decrease represents a 10%

dose decrease.

Once the CRI weaning process is initiated, make sure that thepain medication will be continued with other drugs/route of

injection.

The pain medication should not be discarded when an animal

is feeling better and eating, as it is probably doing so because

it is not painful.

Local analgesiaTo be multimodal, the clinician should always think of local

analgesia to decrease the amount of parenteral analgesia given

and thus side effects. For example, epidural analgesia may be

useful in cases of fractures of the pelvis or hind limbs. It providesexcellent analgesia with minimal systemic effects. Wound

soaker catheters are also an excellent mean to decrease systemic

analgesic given.

ConclusionThe management of pain is a crucial step in the perioperative

management of patients. It helps decrease surgery complications,

promotes healing, decreases length of stay in the hospital and

provides enhanced patient welfare. Everyone is free to devise a

protocol adapted to their own preferences and the equipment

available, but many of the measures described here can be

done cheaply. The clinician should not forget that beside the

administration of medication, the patient must be hospitalised

in adequate conditions of comfort, the owner must be involved

in the recovery process and the nursing team must always think

of providing tender loving care.

References

Dyson DH. Perioperative pain management in veterinary patients. VetClin North Am Small Anim Pract. 2008; 38(6): 1309-27

Lamont LA. Multimodal pain management in veterinary medicine: thephysiologic basis of pharmacologic therapies. Vet Clin North AmSmall Anim Pract. 2008; 38(6): 1173-86

Hansen BD. Analgesia and sedation in the critically ill. Journal ofVeterinary Emergency and Critical Care. 2005; 15(4), 285 - 294

Muir WW. 3rd, Wiese AJ. et al. Effects of morphine, lidocaine, ketamine,and morphine-lidocaine-ketamine drug combination on minimumalveolar concentration in dogs anesthetized with isoflurane. Am J

Vet Res. 2003; 64(9): 1155-60.Mathews KA. Neuropathic pain in dogs and cats: if only they could tell

us if they hurt. Vet Clin North Am Small Anim Pract. 2008; 38(6):1365-414.

If volumes are substantial regarding the size of the bag, the

equivalent volume to be added must be discarded before adding

the drug (it is always the case for a lidocaine CRI).

Ketamine CRIat 0.6mg/kg/h for a 20 kg dog over 25 hours.

Add 3 ml of ketamine to a 250 ml NaCl 0.9% bag.Run at 10 ml/h.

Ketamine (3 ml) represents a tiny volume compared to 250 ml

so it can be added to the bag without discarding the equivalent

volume.

Lidocaine CRIat 50 g/kg/min for a 20 kg dog over 25 hours.

Take a 250 ml bag, discard 75 ml (leaving 175 ml).

Add 75 ml of lidocaine to the remaining 175 ml NaCl 0.9%.

Run at 10 ml/h.

In this case, the amount of lidocaine (75 ml) is significant

compared to 250 ml therefore the equivalent volume to be

added must be discarded from the 250 ml bag first.

The MLK (Morphine, Lidocaine, Ketamine) CRI The MLK

is an example of a multimodal analgesia commonly used in the

perioperative setting. Any combination of analgesics and co-

analgesic is possible. A variation of MLK can be FLK (Fentanyl

Lidocaine Ketamine), MDK (Morphine, Dexmedetomidine,

Ketamine) or any association of an opiod and a co-analgesic.

MLK is a combination of an opioid (morphine), a local

anaesthetic that stimulates peristalsis and is supposedly effective

for reperfusion injuries and ketamine, which is a co-analgesic

that has demonstrated analgesic properties at low doses. As

the use of lidocaine CRI is controversial in cats, it is advisable to

use MLK CRIs only in dogs. MK (Morphine-Ketamine) or MDK

(Morphine-Dexmedetomidine-Ketamine) can be used instead in

cats. Most often, it is convenient to run the CRI at 5 ml/h for

small dogs (to avoid fluid overload) and 10 ml/h for medium size

to large size dogs, but any option is possible.

MLK Rate Drug Concentrationmg/ml

5 kg dog over25 hours

10 kg dog over25 hours

20kg dog over25 hours

Morphine 0.1 mg/kg/h 10 12.5 mg = 1,25 ml 25 mg = 2.5 ml 50 mg = 5 ml

Lidocaine 50 g/kg/min 20 375 mg = 18.75 ml 750 mg = 37.5 ml 1500 mg = 75 ml

Ketamine 0.6 mg/kg/h 100 75 mg = 0,75 ml 150 mg = 1.5 ml 300 mg = 3 ml

For a 5 kg dog:

At a rate of 5 ml/h, the total volume to go over 25 hours is 125

ml.

Take a 100 ml NaCl 0.9% bag, add 1.25 ml of morphine, 18, 75

ml of lidocaine and 0.75 ml ketamine. This volume, 120 ml (100

+ 1.25 + 18.75 + 0.75 ), will be enough to cover 24 hours.

For a 10 kg dog:

At a rate of 10 ml/h, the total volume to go over 25 hours is

250 ml.

Take a 250 ml NaCl 0.9% bag, remove (2,5 + 37,5 + 1,5) 41,5

ml and add 2.5 ml of morphine, 37,5 ml lidocaine and 1.5 ml ofketamine.

CRI weaning:

The rate of morphine should be adjusted based on the level of