ANALGESIA FOR PEDIATRIC PATIENTS
Karol
A. Mathews DVM, DVSc
Quick Links:
Local Anesthetics – General Considerations
Non-steroidal anti-inflammatory Analgesics
Table 1: Drug Dosages for Pediatric Patients
In this discussion the term pediatric generally refers to the first six months of life. Due to important physiologic changes which occur during this time frame, a further demarcation has been defined: neonatal (0-2 weeks), infant (2-6 weeks) weanling, (6-12 weeks) and juvenile (3-6 months). This distinction is mentioned to make the reader aware of the metabolic changes that are occurring during these periods of maturation. Animals between 3 to 6 months of age appear to require the adult dosing to effect analgesia.
There tends to be apprehension in administering analgesic drugs, especially opioids, to young animals due to the often cited ‘decreased drug metabolism and high risk of overdose’. While this may be true in the neonate, it is not necessarily so through all stages of maturation. Based on the human literature, the analgesic requirement may be higher than the adult at a certain stage of development, especially in the pediatric human patient3. Personal experience with intensive monitoring of the rare young (4-6 month old) animal, which inadvertently received ten times the recommended opioid dose, revealed no adverse effects; on the contrary, these animals appeared very comfortable! This is not to suggest that the opioid dose should be increased but to emphasize that administering the analgesic to effect, rather than a pre-determined dose is the most important method by which to manage pain. Opioids can be reversed with naloxone should there be clinical evidence of this (see Analgesic Drugs and Modalities: Opioid antagonism); CNS depression associated with respiratory depression, bradycardia and hypotension. As the effects of the opioid occurs quite rapidly after administration, it is wise to monitor for potential adverse effects rather than reverse a ‘potential’ problem which may not happen.
Neonates, and potentially infants, need to be considered separately from the weanling or juvenile patient when considering analgesics and the following concise review highlights the important aspects6. Neonates do feel pain and, in fact, the nociceptive threshold to some tests may be lower than adults; this may be due to delay in development of the descending inhibitory mechanism which is present later in the maturation process. Due to the slower development of some neurotransmitters or receptors, certain drugs may not be effective at this stage of development. For example, as the NMDA system appears to be underdeveloped in the neonate, ketamine may not be effective. Lower doses of fentanyl or morphine are required for analgesia in the neonate when compared to the 5 week old puppy. Puppies are also more sensitive to the sedative and respiratory depressant affects of morphine and it is recommended that fentanyl may be a more suitable opioid in the very young, especially, the neonate. In addition to the development of the nervous system, the hepatorenal system continues to develop until 3 to 6 weeks of age; this may result in reduced metabolism and excretion altering dosing and dosing intervals2. The presence of milk in the stomach and absorption of medication from the gastrointestinal tract is also altered, potentially resulting in lower blood levels.
An important fact to consider is that results of several studies in neonates and infants have revealed that when pain was experienced and not managed at this young age, this lead to altered pain sensitivity, stress disorders, increased anxiety and attention deficit hyperactivity disorder leading to impaired social skills and patterns of self-destruction behaviour. Subsequent painful experiences, such as vaccination resulted in the experience of more pain (higher pain scores) than children that had not received a previous painful experience without receiving adequate pain management (circumcision for example). These studies suggest that infants retain a memory of a previous painful experience and their response to a subsequent painful stimulus is altered. This has also been shown in laboratory animals and there is no reason to believe this to be any different in cats and dogs5.
The most frequently used anesthetic is lidocaine in human medicine and may be so in veterinary medicine. Infiltration of lidocaine is extremely painful even with 27 – 30 gauge needles, especially in the neonate or pediatric patient7. To reduce pain, buffering, warming (37° to 42°C) and slow administration is recommended. Buffering can be accomplished by mixing 1% lidocaine with sodium bicarbonate at a 10:1 ratio (1 ml 1% lidocaine with 0.1 mEq [0.1 ml of 1 mEq/ml] sodium bicarbonate). As most veterinary practices have a 2% solution, this can be diluted 1:1 with 0.9% sodium chloride (1% = 10 mg/ml) and mixed with sodium bicarbonate to a further 10:1 (lidocaine: sodium bicarbonate see above) ratio prior to administration. It might be advisable to use a maximum dose of lidocaine to be administered to kittens at 3 mg/kg in the neonate to 6 mg/kg to the older pediatric and 6 mg/kg in the neonatal pup to 10 mg/kg in the older pediatric. The lower dose is required because of the immaturity of the nerves, not that the younger animals are at any greater risk of toxic side effects. This dose should be diluted in 0.9% saline for accurate dosing, ease of administration and distribution over the site. Bupivacaine may also be used (see Local Anesthetics General Considerations for indications) with a 2 mg/kg maximum dose in the older kitten and puppy with half this dose advised for the neonate and weanling. Buffering (0.01 mEq/kg sodium bicarbonate) and warming should be carried out as described for lidocaine.
The most frequently used topical cream local anesthetic in our institution is EMLA (Eutectic Mixture of Local Anesthetic) cream. This consists of lidocaine 2.5% and prilocaine 2.5% combined with thickening agents to form an emulsion. Dosing is calculated in a similar manner to the injectable formulation. Local anesthetic concentrations are described as weight by volume (grams/100ml), therefore the 2% solution will be 2,000mgs/100mls = 20mg/ml, which applies to the creams and gels. This product is not sterile and should be used only in intact skin to provide anesthesia for IV catheter placement, blood collection, lumbar puncture and other minor superficial procedures. EMLA cream should be covered with an occlusive dressing for at least 20 minutes and preferably longer. In children, the peak effect is at 2 hours, however, our experience in animals is that 30 minutes facilitates such procedures as jugular catheter placement using the Seldinger technique; however a longer dwell time might be necessary in the more active animal. Another solution, in gel form, is a mixture of lidocaine 4%, epinephrine 0.1% and tetracaine 0.5%, which can be applied to broken or intact skin7. Due to the epinephrine content, this should be avoided in end-arterial regions and mucous membranes. I personally have no experience with this product and there are no published pediatric veterinary studies. The advantage with these products is that no injection is required. Both products should be covered, after application, for approximately 20 minutes. Lidocaine 2% is also available in a sterile gel, in a cartridge. This is frequently used in our institution for desensitization of the vaginal vault prior to urinary catheter placement in female cats and dogs. It may also be applied to the penis prior to urinary catheter placement.
The use of sedatives should be used with caution in young animals, especially when less than 12 weeks of age4. The phenothiazine tranquilizers (ie Acepromazine) undergo little hepatic biotransformation and may cause prolonged CNS depression. These agents are not analgesic, in fact may increase the level of pain if analgesics are not co-administered. These drugs induce peripheral vasodilation and hypotension and hypothermia may result. If these drugs are required, and there may occasion for their use, reduce the dose to 0.005 – 0.025 mg/kg IM or SC. It is advised that the concentration of 10 mg/ml commercial product be diluted to 1 mg/ml prior to withdrawing for administration to facilitate accurate dosing. Opioids have sedating effects, especially in young animals; therefore, if these drugs are required the addition of a sedative may not be necessary in animals younger than 4 months.
In veterinary patients, it has been recommended to administer half the usual adult dose of these agents to puppies and kittens. However, based on human pediatric studies, this will depend on the degree of pain and the phase of maturation. Starting at lower dosages and increasing to effect is recommended. Reversal of any adverse effects may be titrated using naloxone (see analgesic Drugs & Modalities: Opioid antagonism). The dosing recommendations below are ranges published for dogs and cats. Fentanyl transdermal patches and fentanyl ‘lollipops’ (transmucosal) are administered to children1. No veterinary studies are available in this young group of patients assessing these routes of administration. Refer to Analgesic Drugs & Modalities: Opioids for details on these drugs.
Non-steroidal
anti-inflammatory Analgesics
These agents are not recommended for animals less than 6 weeks of age based on developing hepatorenal system. However, until studies confirm the safety of these agents in animals less than 12 weeks of age, their use should be avoided, unless warranted due to difficult to manage pain with opioids alone. Cyclooxygenase-2 is important in sodium and water metabolism at the level of the kidney and it is important to ensure that this system is fully developed prior to administration of NSAIAs. Refer to Drugs & Modalities: Non-steroidal anti-inflammatory analgesics for details and dosages on these drugs.
Table
1: Drug Dosages for Pediatric Patients
|
Drug |
Species |
Dose mg/kg (lower dosages less than 4 weeks of age) |
Route of Administration (SC suggested for less than 4 weeks of age) |
Interval (hours) |
|
Mild to Moderate Pain: |
||||
|
Opioid Agonists: |
||||
|
Morphine |
Dog |
0.1-0.5 0.05+ 0.25+ |
IM, SC, Very Slowly IV IV, SC/hr PO titrate to effect |
1-4 CRI 4-6 (8) |
|
Cat |
0.05-0.1 0.025+ 0.25+ |
IM, SC IV, SC/hr PO titrate to effect |
1-4 CRI 4-6 (8) |
|
|
Methadone |
Dog & Cat |
0.1-0.5 |
IV, IM, SC |
1-4 |
|
Oxymorphone |
Dog & Cat |
0.02-0.05 |
IV, IM, SC |
2-4 |
|
Hydromorphone |
Dog & Cat |
0.02 |
IV, IM, SC |
2-4 (6) |
|
Fentanyl |
Dog & Cat |
0.002-0.010 0.001-0.005 |
IV loading IV/ 20-60 min. |
0.5-1 CRI |
|
Meperidine |
Dog & Cat |
2-5 |
IM |
0.5-1 |
|
Opioid
Agonist-Antagonists: |
||||
|
Butorphanol |
Dog |
0.1-0.2 |
IV, IM, SC |
1-4 |
|
Cat |
0.1-0.2 (or to effect) |
IV, IM, SC |
1-4 |
|
|
Dog & Cat |
0.05-0.01+ |
IV, SC/hr |
CRI |
|
|
Administer IV in 0.01-0.05 mg/kg increments
every 2-3 minutes for reversal of opioid side effects. However, I prefer the naloxone protocol
below. |
||||
|
Opioid Partial Agonists: |
||||
|
Buprenorphine |
|
5-10 mcg/kg |
SC |
~ 6 |
|
Moderate to Severe Pain: |
||||
|
Opioid Agonists: |
||||
|
Morphine |
Dog & Cat |
0.5-1+ 0.05+ 0.5+ |
IM, SC, Very Slowly IV IV, SC/hr PO titrate to effect |
1-4 CRI 4-6 (8) |
|
Cat |
0.1-1 0.05+ 0.5+ |
IM, SC IV, SC/hr PO titrate to effect |
1-4 CRI 4-6 (8) |
|
|
Methadone |
Dog |
0.5-1+ |
IM, SC, IV |
1-4 |
|
Oxymorphone |
Dog & Cat |
0.05-0.1+ |
IV, IM, SC |
2-4 |
|
Hydromorphone |
Dog & Cat |
0.05-0.1+ |
IV, IM, SC |
2-4 (6) |
|
Fentanyl |
Dog & Cat |
0.005-0.010+ 0.001-0.005 |
IV loading IV/ 20-60 min. |
0.5-1 CRI |
|
Meperidine |
Dog & Cat |
2-5 |
IM |
0.5-1 |
|
Opioid Agonist-Antagonists: |
||||
|
Butorphanol |
Cat |
0.3-0.8 (or to effect) 0.2-0.4 |
IV, IM, SC IV/hr |
1-4 (6) CRI |
|
Administer IV in 0.01-0.05 mg/kg increments
every 2-3 minutes for reversal of opioid side effects. However, I prefer the naloxone protocol
below. |
||||
|
Naloxone – Opioid Antagonist Naloxone should always be available
when opioids are used. The dose depends on the administered opioid, dose and
duration. I start by slowly titrating naloxone IV, in 0.004-0.04 mg/kg
(0.01-0.1 ml of 0.4 mg/ml solution) increments until desired clinical
response is achieved. For easy titration, combine 0.05 - 0.1 ml naloxone with
10 mls 0.9% saline. May have to
re-dose at varying intervals, as duration of opioid action is longer than
naloxone. |
||||
|
Sedatives: |
||||
|
Midazolam |
Cat & Dog |
0.05-0.1 |
IV, IM |
Dog up to 6h Cat can be >6h |
|
Diazapam |
Cat & Dog |
0.05-0.1 |
IV |
Dog up to 6h Cat can be >6h |
|
Acepromazine |
Cat & Dog |
0.01-0.025 |
IM, SC |
2-6 |
1. Ball A, Ferguson S. Analgesia and analgesic drugs in paediatrics. Br J Hosp Med. 1996;55(9):586-590
2. Boothe DM & Bucheler Jorg. Drug and blood component therapy and neonatal isoerythrolysis. In:. Veterinary Pediatrics:Dogs and cats from birth to six months. Johny Hospkins(ed.). Philadelphia, WB Saunders. 2001 pgs35-56
3. Collins JJ, Palliative care and the child with cancer. Hematol Oncol Clin N Am 2002;16:657-670
4. Hosgood G. Surgical and anesthetic management of puppies and kittens.Comp Contin Edu.1992;14(5):345-357
5. Lee BH. Managing pain in human neonates – application for animals. J Am Vet Med Assoc. 2002;221(2):233-237
6. Pascoe PJ. Perioperative Pain Management. Vet Clin N Am: Sm Anim Pract 2000;917-932
7. Rodriguez E. Jordan R.Contemporary trends in pediatric sedation and analgesia. Pediatric Emergency Medicine: Current concepts and controversies. Emergency Med Clin of N Amer. 2002;20(1):199-222