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334 J.M. Berger

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Thoracotomy pain can be blocked with paravertebral catheters, as can the pain from mastectomy surgery. Of signiﬁcance is that in a recent report woman undergoing mastectomy for tumor removal had one-fourth the risk of metastatic recurrence when surgery was performed with a continuous paravertebral catheter. The catheter was placed at T2-3 through which a bolus of local anesthetic was given followed by a continuous infusion of local anesthetic. These patients also received general anesthesia with intravenous propofol. This group of patients was compared with a group that received general anesthesia alone [141]. The general anesthesia group had sevoﬂurane, fentanyl, and morphine with a postoperative morphine PCA. The paravertebral catheters were removed after 2 days.

Surgery and tissue injury cause the release of prostaglandins, histamine, potassium, hydrogen, oxygen radicals, bradykinins, substance P, and multiple cytokines involved in chemotaxis [141]. Vallejo also states that some opioids such as heroin inhibit the induction of nitric oxide, a molecule with a critical role in the regulation of immune response and resistance to infection challenges. Therefore, the above study supports that regional anesthesia may not only reduce the stress response associated with surgery, but also avoid anesthetic agents that may directly affect the immune response during the perioperative period, creating a friendlier cytokine environment. It is therefore important that regional anesthetic techniques be employed in a preemptive manor in tumor surgery instead of solely for postoperative pain management.

These blocks allow for unilateral analgesia, facilitating movement, and rehabilitation without the necessity of a Foley catheter. In addition, patients can safely be sent home with continuous catheters and infusions of local anesthetic, pulling the catheters out themselves when the disposable pumps are empty [142].

Just as postoperative epidural analgesia requires the participation of the anesthesiology department of the hospital, so does a peripheral nerve block service. Such a service is predicated upon the anesthesiology department having the expertise and personnel to oversee such a service.

Unfortunately, unlike epidural analgesia which can in fact provide complete analgesia without the need for supplemental intravenous or oral opioid analgesia (since opioids are administered spinally), peripheral nerve blockade cannot be used to completely eliminate the need for supplement opioid analgesics. In order to have complete analgesia, the local anesthetic dose would have to be high enough for a complete sensory blockade which is undesirable. The technique is designed instead to provide adequate analgesia that patients can be discharged from the same day of surgery to home, or remain in the hospital with the need for only oral opioid and anti-inﬂammatory analgesic supplementation. Decreasing the opioid analgesic requirements can result in reduced side

effects such as nausea and constipation. Patient satisfaction is high with these techniques, and the incidence of complications is relatively low [143, 144].

In some orthopedic surgeries, bone graft may be harvested from the iliac crest. This can cause severe pain, which extends far out from the surgical procedure, and can become a chronic problem. It has been shown that the injection of morphine percutaneously into the prospective donor site can produce both immediate postoperative pain relief and long-term beneﬁt [145, 146].

Although the mechanism of the long-term beneﬁt of this technique is not known, there are at least three nerves that can be injured or entrapped in scar tissue at the donor site, the lateral femoral cutaneous nerve, the ilioinguinal nerve (retraction), or the superior cluneal nerves. It is possible that morphine inhibits sensitization of the nerve ﬁbers. This author uses 10 ml of 1% ropivacaine with 2.5–3 mg of morphine injected by the surgeon along the iliac crest percutaneously prior to skin incision for the bone graft harvest.

Multimodal Techniques for Acute Postoperative Pain Management in the Elderly

Because patients rarely present with pure nociceptive pain (i.e., pain caused by activity in the neural pathways in response to damaging or potentially damaging stimuli) or neuropathic pain (i.e., pain initiated by a primary lesion or dysfunction in the nervous system), but rather, have a mixed pain syndrome (i.e., pain caused by a combination of both the primary injury and secondary effects), a rational polypharmacy approach that targets key peripheral and central pain mechanisms and modulating pathways may yield the best outcomes [147].

Oral Administration

Once pain is controlled and bowel function restored, analgesics should be changed to the oral route. Depending on individual variability and the type of surgery, this transition should occur 3–8 days after the surgery. Occasionally patients require parenteral or epidural opioids for a more prolonged period, usually because of intervening complications. Typically, patients require oral opioids for 5–10 days after parenteral or epidural opioids are discontinued. A certain percentage of patients, especially after more painful surgeries, require oral opioids for 2 weeks or longer [41].

Oral analgesics such as oxycodone or codeine are appropriate choices for a patient with mild-to-moderate pain [148].

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Fixed combinations with nonopioid analgesics can be useful, but they sometimes limit the careful individualized titration that is the basis of therapeutic success. The oral transmucosal route may prove effective for rescue doses, but absorption is probably inadequate for more sustained relief. This latter statement also holds for the rectal route, which, additionally, is often uncomfortable for the patient and the caregiver.

One example of the difﬁculty with combination medications is conversion from intravenous PCA to oral. As seen in Table 26.4, the oral equivalent of hydrocodone to 10 mg of

intravenous morphine is 30 mg. The usual combination of hydrocodone with acetaminophen is 5 and 500 mg, respectively. Therefore, six tablets of this combination drug would be necessary to equal 10 mg of intravenous morphine.

In patients suffering from continuous cancer pain, Foley

recommended that the opioid analgesic should be administered regularly, including waking the patient from sleep at intervals based on the duration of analgesia for the given drug. This approach keeps the patient’s pain at tolerable levels and often results in a reduction in the total amount of medication taken during a 24-h period [149]. In elderly patients with acute postsurgical pain, disrupting sleep to provide pain medication on a time contingent basis may be more detrimental than helpful. When the pain is present only during particular activities (e.g., physical therapy) or at particular times of the day, the opioid should be administered on an as-needed basis. It must be remembered that it takes approximately 1 h to reach peak serum levels after oral administration.

Special Circumstances

Some surgical procedures are associated with a higher risk of postoperative pain syndromes such as phantom limb pain syndrome after amputation. Regional anesthetic techniques offer the greatest protection; however, some patients either decline to have a regional blockade or the blocks are contraindicated for various reasons, and general anesthesia must be administered. General anesthetics alone do not protect the spinal cord from undergoing central sensitization leading to chronic neuropathic pain [150, 151]. But a polypharmaceutical approach, although not proven yet, seems to offer an advantage over traditional anesthetic and postoperative management techniques.

The following recommendations for the example of phantom limb pain prevention with amputation surgery are based on this author’s experience, supported by the available evidenced-based medicine, which although limited in this regard, aims to target polypharmacy in such a way to help the brain modulate neuropathic pain [152]. The recommendations given below for this presented scenario of an amputation

without the beneﬁt of regional anesthesia is similar to the multimodal polypharmaceutical therapeutic recommendations of power, in which he reviews the uses of both opioid and nonopioid analgesics, anticonvulsants, and antidepressants in postoperative pain management [62].

As indicated above, in this author’s experience, agents that have NMDA receptor blocking action like ketamine [153, 154], drugs with Mu opioid agonist action, tetrodotoxin resistance (TTXr) sodium channel blockers such as the local anesthetics, serotonin and norepinephrine reuptake inhibitors such as antidepressants [155–157], and neuronal calcium channel blockers such as the anticonvulsants gabapentin or pregabalin [158–163], and anti-inﬂammatory drugs if not contraindicated (see above), can all contribute to CNS protection. In such a case, preoperative oral gabapentin (Neurontin®) 300–1,200 mg [158–167] or pregabalin (Lyrica®) 75–150 mg, and if available a COX-2 inhibitor celecoxib (Celebrex®) 200 mg, can also be given orally which would alleviate the need for intraoperative ketorolac. It is true that COX-2 inhibitors are controversial with respect to patients at risk for stroke or myocardial infarction which makes up a large percentage of the elderly population. But there does not seem to be evidence that a single preoperative dose of 200 mg of celecoxib would pose a signiﬁcant risk versus the beneﬁt of preemptive analgesia [168].

Glucocorticoids given both preoperatively or postoperatively have been shown to reduce postoperative nausea and vomiting, and to decrease pain [169, 170]. Less than 8 mg of dexamethasone or 150 mg of methyprenisolone intravenously seem to be adequate.

Preoperative oral administration of clonidine, an a2-agonist, reduces postoperative analgesic requirement as determined by IV morphine utilization via PCA after knee surgery [171], but not after major abdominal surgery [172]; whereas analgesia from intrathecally administered morphine was enhanced by oral clonidine premedication after total abdominal hysterectomy [173].

The recommended dose of gabapentin should be reduced from that given in the above references when dealing with the elderly population. Again this is an empiric decision of the author since the preoperative dose that would be appropriate in elderly patients has not been determined. But gabapentin and pregabalin have both been used in patients of all ages for the treatment of such conditions as postherpetic neuralgia [174]. Gabapentin in a dose of 600 mg preoperatively has also been found to decrease the incidence of nausea and vomiting and reduce the postoperative opioid requirements in a study of laparoscopic cholecystectomy patients [175].

Intraoperatively, the anesthesiologist (again in this author’s experience) can administer several adjuvants that will also assist in protecting the spinal cord from excessive nociceptive input. Methadone would be a good choice for an opioid because of its NMDA receptor antagonist effect but it is often

336 J.M. Berger

Anticholinergic effects (sedation) Dose range Tolerability

Tricyclics

Amitriptyline (Elavil®) Least effect 10–25 mg qhs Desipramine (Norpramin

) Least effect 10–25 mg qhs

Best

Doxipin (Sinequan

) Most effect

Most sedating

Imipramine (Tofranil

) Intermediate 10–25 mg/day

Best

Nortriptyline (Pamelor

) Intermediate 10–25 mg/day

Best

Non-Tricyclics

Venlafaxine (Effexor®)

³150

mg/day

Duloxetine (Cymbalta

) 30–120 mg/day

Best

Bupropion (Wellbutrin

SR) 150–300 mg/day

Trazadone (Deseryl

) Sleep aid in women 50–300 mg/day

Risk of priapism in men

Note: Dosages are low adjusted for the elderly patient. The antidepressants that are effective in pain management are those that have both serotonin and norepinephrine reuptake inhibition effects. The Tricyclic antidepressants all have these effects but their side effect proﬁles determine the tolerability of these drugs particularly by elderly patients, e.g., anticholinergic effects, sedation. The non-Tricyclic antidepressants that are effective in

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Ta b l e 26.5 Antidepressants in clinical practice (Tricyclic antidepressants)

unavailable and its slow onset of action is not suitable for intraoperative administration. Fentanyl would therefore be a logical choice since it is potent and more easily titrated due to its rapid onset of action when administered intravenously.

Although the data are not conclusive there is data to show that magnesium ampliﬁes the analgesic effects of low-dose morphine in conditions of sustained pain [176]. Lysakowski et al., in a meta-analysis study of magnesium, concluded that the trials reviewed did not provide “convincing” evidence that perioperative magnesium has a favorable effect on postoperative pain intensity and analgesic requirements. Nevertheless, it may be worthwhile to further study the role of magnesium as a supplement to postoperative analgesia, since this molecule is inexpensive, relatively harmless, and the biological basis for its potential antinociceptive effect is promising [177]. There is a possibility that magnesium might have an additive or even synergistic effect with other NMDA antagonists, speciﬁcally ketamine although the optimum dose is not established [178, 179].

Considering the good tolerability of magnesium, these ﬁndings may have clinical application in neuropathic and persistent pain. Again the appropriate dose of magnesium is not known, but 30

mg/kg IV intraoperative administered prior to skin incision seems to be safe even in the elderly population. In combination with low-dose gabapentin, signiﬁcant improvement in the effectiveness of morphine is observed in a rat model of nerve ligation neuropathic pain [166]. Referring to the above-stated preoperative dosing of gabapentin, the two should enhance the protective analgesic effect of the opioid used.

Low subanesthetic doses of ketamine (0.10–0.2 mg/kg IV intraoperative preincision) can be used for as part of the intravenous induction, and repeat doses q2h intraoperative can provide additional inhibition of activation of spinal cord

NMDA receptors. Midazolam preinduction can reduce anxiety and also has an antagonist site on the NMDA receptor. As previously stated, if the patient is unable to take a COX-2 inhibitor (celecoxib), then ketorolac 7.5–15

mg should be given prior to amputation intraoperatively and continued q6h intravenously for 48 h. Lidocaine 1.5 mg/kg IV at the time of skin incision and repeated during the amputation as a general sodium channel blocker can all be helpful.

Postoperatively, the antineuropathic regimen should be continued until the wound (stump) has healed in terms of continued gabapentin or pregabalin (100–300 mg tid or 50 mg tid, respectively) along with an appropriate opioid, anti-inﬂammatory, and antidepressant (for serotonin and norepinephrine reuptake inhibition action).

Antidepressants that have been used in pain management are listed below (Table 26.5) along with starting doses and tolerability [147]. In summary, amitriptyline is probably the most studied in pain management and its efﬁcacy is well established. Of the newest antidepressants that have been studied in pain management, duloxetine (a non-Tricyclic) is well tolerated with a fast onset of effect after the initiation of treatment [

147].

Addiction, Dependence, Tolerance, and Pseudoaddiction

The fear of addiction or psychological dependence is one of the major barriers to the appropriate management of pain in the USA. Psychological dependence is the development of drug-seeking behavior that persists despite harm to the patient or others. Such drug-seeking behavior includes the hoarding of medication, use of medication for purposes other

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a b l e 26.6 Choosing the best option for postoperative pain control in the elderly

Cognitively intact Cognitively impaired

More painful procedures (e.g., thoracotomy, complex abdominal/pelvic surgery)

Epidural: lipophilic opioid (e.g., fentanyl) plus local anesthetic as a

continuous infusion with or without epidural PCA or

Intravenous: strong opioid as an intravenous infusion

with intravenous PCA

Epidural: opioid plus local anesthetic as a continuous infusion without

PCA or Intravenous: strong opioid as a continuous infusion without PCA, or

nurse administered “PCA” without a basal rate based on patient

assessment

Less painful procedures (e.g., lower abdominal surgery, hip/knee replacement)

Intravenous: strong opioid via PCA or given intravenously every 4–6 h Epidural: opioid plus local anesthetic as a continuous infusion without

If appropriate for the surgery, continuous peripheral nerve blocks with

supplemental oral medications

Continuous epidural or peripheral nerve block techniques offer the best control of postoperative pain in the elderly patient but if not appropriate or contraindicated, then intravenous administration must be utilized. Transition to oral medications must be adequate to control pain prior to discharge. When intravenous access is not available and the oral route cannot be used, the subcutaneous route is better than the intramuscular route. When the subcutaneous route is used, the absorption is less erratic with hydromorphone (more lipid soluble) than with morphine. For intermittent dosing, it is best to use an insulin syringe. For continuous infusion, a 27-gage butterﬂy needle can be used. Postoperative orders for pain medication should be standing rather than PRN. The remarks “hold for excessive sedation” and “patient may refuse” add a safety valve to the order

PCA patient-controlled analgesia Source: Data from Morrison et

al. [41]

PCA or Intravenous: strong opioid as a continuous infusion without PCA If appropriate for the surgery, continuous peripheral nerve blocks with

supplemental oral medications

than control of pain, and obtaining opioids from multiple sources. It is important to distinguish true psychological dependence from “pseudoaddiction” [180], which can develop in patients who are undermedicated for their level of pain. Pseudoaddiction is drug-seeking behavior motivated by a need to obtain enough analgesia to control pain. When pain is appropriately managed and adequate analgesia provided, the behavior disappears. Although further research is needed, it appears that the incidence of psychological addiction in patients without a history of substance abuse and treated with opioids for control of pain is rare [69]. Fear of addiction should never limit the use of opioids for pain control in the elderly patient who has no history of substance abuse [41].

Conclusion

As aptly stated by Morrison, Carney, and Manfredi, in the ﬁrst edition of this book, “good pain management in the elderly surgical patient is a complex, challenging undertaking of critical importance. Ensuring adequate analgesia requires an understanding of age-related changes in pharmacokinetics and pharmacodynamics, pain physiology, the appropriate use of analgesic agents, and knowledge of these agents’ limitations and side effects. Unfortunately, few studies have focused on the assessment and treatment of pain in elderly individuals, and guidelines for analgesic therapy are often based on the experiences of young and middle-aged adults. Further research involving pain in the elderly is critically needed given the evolving changes in population demographics (persons over

65 represent the most rapidly growing segment of the US population) and the increasing rates of surgery in this population. Until such research is completed, clinicians must continue to interpret the available data in the context of their knowledge of age-related physiologic changes, medication effects, side effect proﬁles, and clinical experience. This approach is summarized in Table 26.6 and results in appropriate pain management for most elderly surgical patients” [41]. The increased use of regional and peripheral nerve block techniques holds much promise for acute postsurgical pain management in the elderly population, as does our increasing knowledge of the pathophysiological mechanisms of pain translating into advances in the polypharmaceutical multimodal approach to pain management.

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