Pain Intervention 101 Techniques

PCA is a computerized, self-administered delivery system first used in adults. Children as young as 5 years old can appropriately use the apparatus. This technique allows for single loading doses and continuous background infusions to be administered in addition to the PCA bolus dose (104). The use of continuous nighttime infusions added to PCA have shown improved sleep and analgesia (105). However, the use of around-the-clock, continuous background infusions have been associated with higher PCA intake (106). PCA has been adapted for use by parents and caretakers for toddlers and older children who are not cognitively or physically capable of executing the self-activated PCA demand button. PCA by proxy has been administered as nurse-controlled or parent-controlled analgesia yet has been associated with a higher incidence of side effects, with oversedation the main adverse event.

In an observational study by Monitto et al., 4% of patients required naloxone reversal of sedation or apnea (107). Nurse-controlled analgesia has been safely administered in children with severe cancer pain. Patients with cancer or prolonged opioid exposure may require higher infusion rates (108). However, the higher the total 24-hour dose, the more likely the occurrence of side effects. Nausea and vomiting are dose-dependent and can be decreased with opioid-sparing techniques.

Epidural analgesia has been shown to provide better patient satisfaction and lower pain scores than intravenous opioid analgesia (109,110). Combinations of local anesthetics with opioids or a-2 agonists provide profound analgesia with minimal sedation or respiratory depression.

Thoracic, lumbar, and sacral approaches to the epidural space have been described (111). The thoracic approach via the caudal space is possible in the infant and young child because the loose areolar fat and connective tissue yield little resistance. Success in obtaining the desired level via distal entry is enhanced with nerve stimulation guidance (112). The actualization of epidural anesthesia is often performed under general anesthesia. The risks of undetected nerve root trauma or spinal cord insult in the anesthetized patient is a theoretical concern. However, actualization under general anesthesia has proven to be a safe practice (113). Further advances in the use of epidural and other regional techniques in children has proven to be safe and desirable for medical, perioperative, and trauma-related pain management in children.

The degree of bacterial colonization increases from the lumbar to the caudal region and poses a risk to neuraxial infection with the transfer of skin flora into the caudal space. Tunneled catheters can remain in situ for months without significant risk of infection (114). Various barrier techniques have been tried in an effort to prevent contamination of the epidural space (115). Tunneled caudal catheters reduce the risk of infection. A study by Bubeck revealed that caudal catheters that were not tunneled had three times the rate of colonization (116).

Peripheral nerve blocks have fewer side effects than major conduction blocks, such as epidural analgesia. However, transient nerve damage, local anesthetic toxicity, and inadequate blockade are concerns (117-119). Patient-controlled regional analgesia has been reported to provide safe analgesia for postoperative pain control after lower limb surgery (120).

10.1.1. Analgesics and Adjuvants

10.1.1.1. Opioids

Morphine is the gold standard for strong opioids. As the prototype, morphine equivalents is the comparative term for converting all opioids into a user-friendly language (Table 2). The half-life of morphine is 114 minutes. Morphine sulfate (MSO4) is metabolized by glucuronidation. Major metabolites of morphine include M-3 glucuronide, which is neutral or possibly antalgesic, and M-6-glucuronide, an active metabolite with an elimination half-life of 173 minutes (121). The clearance of opioid is three to five times slower in infants younger than 3 months than in adults. Infants at 1-4 days show longer elimination half-lives than older infants (6.8 vs 3.9 hours). This difference can lead to accumulation and possibly toxic plasma levels with repeated dosing (121,122). Infants older than 3 months will metabolize morphine like adults (123).

Decreased responsiveness of pain to opioids may be seen in neuropathic pain because of hyperalgesia, by which the mechanism of upregulation of neurokinin-1 and substance P receptors is implicated (124). G proteins form a superfamily of essential regulators that signal myriad cellular activities, including transduction, organization of the cytoskeleton, and ^ opioid receptor function. Upregulation of the regulator of G protein signaling can lead to a decrease of signaling in G/Go coupling of the opioid receptor (125). This results in both hyperalgesia and decreased responsive to opioids. Hence, neuropathic pain can be associated with reduced opioid antinociception from multiple mechanisms. Methadone has seen resurgence because of its N-methyl-D-aspartate receptor antagonism because it reduces opioid tolerance and restores ^ receptor activity and analgesia (126).

10.1.1.2. Nonsteroidal Anti-Inflammatory Drugs

NSAIDs are important to acute and chronic pain management (Table 3). The NSAIDs, when used in conjunction with opioids, are valuable in the improvement of postoperative pain by causing the opioid-sparing effects and greater reduction in pain scores (127-129). The risk of perioperative bleeding does not appear

Table 3

Nonopioid Analgesics

Table 3

Nonopioid Analgesics

Drug

Dose (mg/kg)

Route

Formulation

Comment

Acetaminophen

10-15 q 4 hours

po

Liquid, tablets

Limited anti-inflammatory effect

Acetyl salicylic acid

10-15 q 4 hours

po

Tablets (chewable)

Associated with Reye syndrome Antiplatelet effect, GI upset

Choline magnesium

trisalicylate (Trilisate)

25 q 8-12 hours

po

Liquid, tablets

Less GI upset and antiplatelet effect than other NSAIDs

Ibuprofen

5-10 q 6 hours

po

Liquid, tablets

Antiplatelet effect, GI upset; interstitial nephritis and hepatic toxicity with chronic use

Indomethacin

1 q 8 hours

po, iv, pr

Liquid, tablet, suppository

Used in premature infants to close patent ductus arteriosus

Ketorolac

0.5 (load)

iv, im

Intravenous

Limit to 48-72 hours; only NSAID

0.5 q 6 hours

iv, im

approved for parenteral analgesia; costly

10 (total dose) q

po

Tablets

vs ibuprofen

6 hours

Naproxen

5-10 q 6-8 hours

po

Liquid, tablets

See ibuprofen

Celecoxib

100-200 bid

po

Capsules

+ GI, - platelet effect

Rofecoxib (currently

25-50 total qd

po

Suspension, tablets

- GI, - platelet effect

suspended)

or 0.5-0.7 mg/kg

Tramadol

50-100 mg total

po

Tablets

Some sedation, lightheadedness; per

per dose kilogram doses not available for small children

From ref. 153. GI, gastrointestinal; NSAID, nonsteroidal anti-inflammatory drug; im, intramuscular; po, per os (by mouth); iv, intravenous.

per dose kilogram doses not available for small children

From ref. 153. GI, gastrointestinal; NSAID, nonsteroidal anti-inflammatory drug; im, intramuscular; po, per os (by mouth); iv, intravenous.

to be affected by NSAID use (130). Intravenous ketorolac has been administered after congenital heart surgery without complication.

In a study by Gupta et al., 94 children received perioperative doses of ketorolac. A relative risk of 0.2 was found for postoperative bleeding that required surgical exploration (131). Neonatal dosing of ketorolac at 1 mg/kg did not cause bleeding or renal impairment. NSAIDs could prove to be efficacious in neonatal pain (132).

Much attention has been given to cyclo-oxgenase (COX) inhibitors. The study of COX-1 and COX-2 isoenzymes revealed that the COX-1 isoenzyme is constitutive and continuously functioning. The COX-2 isoenzyme is inducible and is inactive in the absence of pathology. Its deleterious effects involve the inflammatory response. NSAIDs that are predominantly COX-2 inhibitors include parecoxib, valdecoxib, celecoxib, and rofecoxib.

The availability of rofecoxib as an oral suspension facilitated pediatric administration. Doses of 0.5-1.0 mg/kg up to a total dose of 50 mg were well tolerated. Children appeared to have pharmacokinetics similar to adults (132). Rofecoxib was voluntarily removed from the market because of an increased incidence of cardiac and central nervous system findings in adults. No comparable untoward findings have been reported in children (133). Angioedema and urticaria have occurred in isolated cases in children taking COX-2 inhibitors for rheumatological disease (134).

Clonidine, an a-2 agonist, has been administered by the oral, neuraxial, and intravenous routes for pain management in various settings. Perioperative pain control and sedation have been demonstrated by oral and rectal routes of administration (135,136). Doses of 5 ^g/kg are typically administered with prophylactic doses of atropine to guard against bradycardia. The literature consistently documents good pain control when clonidine is administered by the intravenous and neuraxial routes (137,138).

The benefits of clonidine as an adjuvant include (1) reduction in the amount of opioid required for analgesia and thus a likely decrease in the side effects caused by opioids; (2) titrated sedation and anxiolysis without additive respiratory depression when given in combination with opioids; and (3) vasodilatation and improved circulation of cerebral, coronary, and visceral vascular beds (139).

Continuous infusion of intravenous clonidine was cited in the literature approximately a decade ago as a safe adjuvant for pain control. The amount of opioids required by patients suffering procedural pain was reduced by 30%. Hemodynamic stability was maintained within normal limits as patients experienced less than a 10% change in mean blood pressure (139).

The use of intravenous clonidine infusions in critically ill children has been reported as safe and efficacious without occurrence of complication or need for intervention or support because of sedation, heart rate, or blood pressure changes (140).

10.1.1.4. Membrane-Stabilizing Agents

The TCAs are used in chronic and neuropathic pain management. These cyclic amines may have intrinsic analgesic properties via cholecystokinin antagonism and may reverse established opioid tolerance (141). The tertiary amines (e.g., amitriptyline) and secondary, demethylated amines (e.g., nortriptyline) have been studied more than the selective serotonin reuptake inhibitors in the treatment of neuropathic pain. TCAs are less expensive than the selective serotonin reuptake inhibitors, making the former more readily prescribed (142).

Antidepressants must be taken orally for weeks to months before the onset of antinociception. When used in acute pain management, antidepressants readily improve sleep hygiene and promote restorative sleep patterns. Intravenous use of amitriptyline for acute control of mucositis pain has been cited as effective (143). Cardiac rhythm changes and orthostasis can occur with intravenous amitriptyline; therefore, use in a monitored setting is encouraged (144).

10.1.1.5. Antiepileptics

AEDs are indicated for neuropathic pain. Like TCAs, delayed effect is to be expected with oral preparations. Intravenous fosphenytoin infusion for 24 hours has been purported to provide good pain relief in the case of postoperative neuroma formation (145).

Generally, AEDs are prescribed for oral administration. The newer AEDs, such as gabapentin and lamotrigine, have less effect on cognitive function than carbamazepine and phenytoin. High-dose gabapentin (25-40 mg/kg/day) has been associated with aggressive behavior in children who have an underlying seizure history. Generally, gabapentin is well tolerated and is prescribed in an off-label fashion in children with neuropathic pain (146). The preemptive use of gabapentin in surgical patients results in reduced opioid requirements (147). AEDs may have a broader application in hospital-based pain care than is currently practiced.

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