飯塚 高弘

Management of Intractable Pain in Extremely Elderly Patients with Lumbar Canal Stenosi NewYork USA 2018 Takahiro IIZUKA MD and Mitsuhiro Matsukawa MD. Department of Orthopaedic Surgery, Kawasaki Hospital 244 Mizuma Kaizuka City, Osaka, JAPAN Key words ; elderly patients, Poor physical condition, Dementia, LCS, Opioid Introduction The management of non-malignant pain in extremely elderly patients is one of the most major concerns in these aging populations. The therapies of the non-malignant pain are often limited because of the poor physical and mental conditions (7). Neuropathic pain, in particular, related to lumbar canal stenosis (LCS) is often more intractable for the lasting pain with numbness and motor dysfunction than rheumatic pain in lower/upper extremities (8). There is strong evidence reported that surgery is the mainstay for such neuropathic pain related to LCS (16,39) However poor physical and mental conditions limit the indication for surgical procedures (8). There is no discussion regarding the management of pain in the patients who could not undergo surgical procedure. Poor physical conditions (dysfunction of kidney and/or liver, and gastrointestinal disorders) limit even the prescription of non-steroidal anti-inflammatory drugs (NSAIDs). Anti-coagulant therapy and liver cirrhosis induced-thrombocytopenia often limit the spinal block therapy (8,20) and several therapies in these populations. Actually the extremely elderly patients beyond the average life span also have little or no ability in decision-making on the choice of the risky treatments because of poor mental status due to dementia. Therefore, failure in the managing continuous endurable pain with LCS in elderly patients reduces the quality of life (QOL) through all the rest of life. However there are few reports on the management of these non-malignant pains in extremely elderly patients. And there have not been discussion on opioids use for extremely elderly patients because of the adverse events of opioids (bowel dysfunction, addiction and respiratory suppression etc). Management of the intractable pain with less invasive methods is of great importance for QOL. We made the conservative strategy for the patients with LCS who rejected surgical procedures or who could not be indicated for surgery according to our step up pain management ladder as WHO's Pain Ladder for malignancy (24). Objectives The conservative management according to our ladder was retrospectively evaluated focusing on the effects, the validity and the safety in order to discuss the efficacy of conservative therapies for non-malignant intractable pain in extremely elderly patients. Patients and Methods Twenty patients (male: 12, female; 8) with LCS more than 80 years old (mean age;85.5y.o.) were enrolled in this study in two years between October 2006 and September 2008. Each patient could not undergo surgery because of poor physical conditions and /or rejected surgical treatments. The benefits and the risks of surgical procedures were informed for the each patient and their families before making decision. They were treated with NSAIDs., spinal block and opioids according to the following Pain Management Ladder. Pain Management Ladder for Chronic Non-Malignant Pain Step1: NSAIDs : oral administration of loxoprofen (60mg/T, 3T/day) and rehabilitation with stabilizing lumbar spine with corset. Step2: Epidural spinal block : Sacral block with 1% xylocaine 5ml, betamethasone 2mg and Saline 10ml per week, intravenous PGE injection and/or intravenous steroid injection (methyl-predonisolone 250mg/100ml saline) at out-patient setting. Step3: Continuous spinal injection (0.25% bupibacaine 1.0-2.0ml/hour) and selective nerve root block (betamethasone 2mg and 1%xylocaine 2ml) at in-hospital setting. Step4: Opioids were administered when patients were not satisfied with Step1-3 or when not continued Step 1-3 therapy because of complications (Pentazocine 25mg/tablet, 2T/day or Buprenorphine 0.2mg /suppository, 2 pieces/day) . Physical conditions were evaluated with American Society of Anesthesiologist (ASA) classification (Table ). And mental status was evaluated with Hasegawa’s Dementia Scoring (HDS) shown in Table . The efficacy of the therapy was evaluated with Visual Analogue Scale (VAS) sore. VAS score was obtained from the main care worker when patients were unable to communicate. The clinical efficacy and adverse events of the each conservative therapy were investigated through the therapy. Japan Orthopaedic Association (JOA) score for lumbar spine (Table ) was used for evaluation of LCS which included subjective, objective symptoms and activity of daily life (ADL). Statistical methods Using analysis of variance and Results The average follow-up periods were 23.1 months. Nine patients (45%) were died (mean age;86.4y.o) of other causes and 11 patients survived (mean age:84.7y.o) through this study (Figure 1). Nine patients died of heart failure (3 patients), pneumonia (3 patients), renal failure (2 patients) and liver cirrhosis (1 patient). The main causes of the neuropathic pain existed in Cauda equina of 5 patients, Nerve root of 8 and Mixed of 7. The pre-medicated JOA score was /29 points (Cauda equina : 12.2 . Nerve root : 15.1 , Mixed : 10.0). Three patients had severe cauda equina syndrome with urinary incontinent (patient , Table ). Physical conditions and ASA classification All of the patients had previous clinical history. Fourteen patients had severe problems in visceral organs (brain, heart, lung, liver, kidney and gastro-intestine). Physical conditions of the patients was classified in grade1 of 1 patient, grade 2 of 7,grade 3 of 6,grade 4 of 6 and grade 5-6 of no patients according to ASA classification. Anti-coagulants limited the choice of spinal block therapy in the seven patients indicated spinal injection (aspirin 100mg/day in 6 patients and warfarin 4mg/day in one patient). Spinal block could not be done because of liver cirrhosis induced-thrombocytopenia in two patients with chronic hepatitis C. Precise data of the each patient was demonstrated in Table . Poor physical conditions, actually, limited the choice of the therapies. Anti-coagulants limited the spinal block therapy in 7 patients. Step 1 therapy for 8 patients included 4 patients who could not have block therapy because of anti-coagulant agents. Step 2 therapy was effective in 3 patients.Step3 therapy was more effective in 2 patients and Step 4 therapy was tried in 7 patients who could not be satisfied with Step1-3. The seven patients in Step 4 treated with opioids had satisfaction of pain relief without major complications Mental conditions and Hasegawa’s Dementia Score (HDS) Every patient had some dementia manifested with memory loss, cognitive dysfunction and behavioral/emotional disturbances. Average HDS was 18.3/30 points. Six patients had severe dementia (HDS<10) who could not communicate and forgot even their own names. Four patients moderate (10<HDS<20) and 10 patients had slight (20<HDS<30) who were forgetful. Figure 2 demonstrated distributions showing two peaks in HDS, which meat there were elderly patients who could make decision and who lost discernment. There was no conviction that patients with slight dementia (even with high Hasegawa’s Dementia Score) understood benefits and risks about the therapies even when informed details. The choice of therapies was determined with a third person in attendance on the patient. Clinical Results (VAS score) and Pain Management Ladder ( Step 1-4 ) All the patients (20patients) underwent Step 1 at first. Nine patients underwent Step 2 because of the poor results of Step1. And seven patients underwent Step2. Seven patients were also medicated opioids (Step 4). Base line VAS score was 8.05(6-9)/10 at Pre-medication, and improved to 6.80(5-9) on Step1. On Step2 Sacral spinal block was performed for 7patients and intravenous steroid injection was for 2patients. VAS score improved to 5.78(1-8) after Step2 therapy. Five patients had Continuous spinal injection for a week and 2 patients had selective nerve root block at in-hospital on Step3. They had not been satisfied through the Step2. They reported satisfaction when they had Step2 therapy and just after block. But the effect did not continue. VAS score was 5.71(2-8). Significantly good results were obtained after Step4 therapy (Step3 vs. Step 4; P<0.05). Seven patients had oral administration of pentazocine 2T/day. VAS score was improved to 3.43(2-4) on Step4 at final follow-up (Figure 4). The therapy was chosen according to Pain Management Ladder when could not achieved satisfactory results. Then, actually, the patients who had stepped up Pain Management Ladder had worse VAS score. Patients divided to four groups by the final Step of the chosen therapy. Figure 5 demonstrated the change of VAS score through Steps (1-4). On Step1, clinical results were not satisfactory with administration of NSAIDs in each group (Figure 5). On Step 4, even the patients who had not been satisfied with the results of Step 2-3 (VAS score was 6-7 on Step 2-3) had relief from pain with opioids (p<0.005). Adverse Events No major adverse events occurred through the therapy. Three patients had NSAIDs induced gastric mucosal lesions on Step1. They recovered soon with proton pomp inhibitor (PPI). On Step2 just after sacral block a patient had nausea (vasovagal response). Four of 7 patients had nausea and vomiting after administration of pentazocine as side effects and discontinued the medication. The opioids switched to buprenorphine 0.2mg /suppository. No nausea and vomiting with buprenorphine were reported. One patient had drug abuse and drug-dependence on Buprenorphine (Patient 18). He was reprimanded severely on usage of buprenorphine. The therapy could be continued through the follow-up periods without major complications. Discussion Strategy for Chronic Non-malignant Pain in Extremely Elderly Patients Relief from intractable pain is philosophically required for QOL in the extremely elderly patients who are more than 80 years old, though to maintain their lives was of grate importance. The main goal of treatment is to improve QOL while decreasing pain. The average age is 79.2 y.o of male and 86.0 y.o. of female in Japan according to Ministry of Health, Labor and Welfare 2007. Chronic pain is significant problem and the age-related metabolic,cognitive and pharmacokinetic changes associated with advanced age make pain control in the elderly a challenge( 7). Conservative non-invasive therapy would provide grate benefits for patients who had little life expectancy. The most important purpose of medicine is the life-support in these ages. It is suggested that there should be a different strategy for pain relief of extremely elderly patients from that of younger patients. Lumbar Canal Stenosis in Extremely Elderly Patients Neuropathic pain, in particular, related to LCS is often intractable for the lasting pain with numbness and motor dysfunction. Surgical decompression has remained a mainstay of therapy because of the poor success in conservative treatments (35,39,34,33). The pathoanatomy is complicated in these generations. Spinal stenosis broadly refers to any site of narrowing in the central canal, lateral recess, or intervertebral foramen. In the elderly patients these type frequently coexist. Pathophysiologically , the dura mater may be mechanically and chemically irritated. A process of chemical inflammation may extend to the adjacent innervated dura mater. The entrapment leads to nerve-root ischemia, and theraby to demyelination and axonal degeneration of the involved nerve fibers, and deafferentation of connected cell in the spinal ganglion. These processes cause neurogenic and neuropathic pains(20). That makes it more difficult to treat LCS in elderly patients (33). Difficulties in Treatment Because of Physical and Mental Poor conditions However surgery is often not the preferred treatment for the patients beyond 80years old except of the unexpected trauma surgery because surgery might affect the life expectancy. Patients by their own will and/or their families often do not hope to have the surgical treatment. There are no reports on the management of these extremely elderly patients. The narrowing of the therapeutic index because of physiological changes in aging can alter the pharmacokinetics and pharmacodynamics of analgesics (7). In this study, while limited in its sample size, we found definitely poor physical conditions of the patients. 19 of 20 patients (95%) ranged from Grade 2 to Grade 4 of ASA classification. We cannot disregard the fact that nine patients (45%) were dead at the final follow up. Therefore, we should be more careful in the surgical indications. And peri-operative complications well influence the choice of the therapy. Anti-coagulants and liver cirrhosis induced-thrombocytopenia limited the choice of spinal block therapy in the patients indicated spinal injection. Surgical procedures and the block therapy are influenced by hemostasis. HDS was 18.3/30points on the average concerning the mental condition. More than the half of the patients had no ability to make decision on the important issues. Because they lost the ability to make decision on the choice of the therapy, the choice of therapies was determined with a third person in attendance on the patient. To inform benefits and risks to patients and the third person (i.e. family member) is the necessary process for confidence and reliance of treatment at the decision (11,30). Pain Management Ladder for Chronic Non-malignant Pain There are many reports on the necessity of treatment plan for non-malignant pain (11,12,40,17,25,30). We made Pain Management Ladder for chronic non-malignant pain (Table ) for LCS because of the physical condition and medicolegal reasons. Choice of opioids for chronic non-malignant pain is still controversial because of the medicolegal and social issues (5,13), despite of the great benefits (2,3,4,6). Japanese Public Health Incurrence does not yet approve opioids for non-malignant pain. The regulatory and legal environment continues to be in a state of flux without uniform (1). And opioids are not accepted in our society because the negative aspects (drug addiction) even in the clinical use (18). Clinicians, patients and families may fear perceive inevitable or substantial side effects (24,30,28). Other general reasons include concern for addiction(18,23,22,31), the specter of medicolegal retribution, social stigmatization, or annoyance (1). There have not been guidelines for responsible use of opioids in chronic nonmalignant pain conditions due to these problems. In facts, drug abuse and addictions are sometimes observed so that clinicians should be more careful in the indications and the management of opioids(13). It is wise for clinicians to have a comprehensive therapeutic armamentarium that includes opioids among other choices. On Step1 pre-medicated VAS (8.05/10points) improved to 6.80 with NSAIDs (roxoprophen). NSAIDs are widely available for any kinds of pain. COx2 inhibitors may be more effective for the management of chronic pain (17). Spinal block and selective nerve block(17,20) are more powerful (39,36) and less invasive for the patients regarding the total amount of the drugs. 　Opioid analgesics, with or without paracetamol,are useful alternatives in patients in whom NSAIDs including COX-2 selective inhibitors are contraindicated ,ineffective,and/or poorly tolerated(30). Selection of Opioids We prescribed opioids analgesics for 7 patients of 20 (35%) in this study, when other medication has failed. We chose pentazocine and buprenorphine because of their less influence on respiration and less dependence/addiction than other opioids (2,7) . They are classified in the partial opioids (mixed agonist-antagonist opioids), which have different effects on various opioid receptors. The major receptors of opioids are known as　μ,κ　and δ-receptors. Pentazocine is a μ-antagonist and κ-agonist synthetic opioid. Buprenorphine is a cantraly acting partial mu agonist and a kappa and delta opioid receptor antagonist(7).Buprenorphine has a high affinity for the mu receptor and lower intrinsic activity than a full agonisit mu opioid receptor agonist.(7) Thus Pentazocine and buprenorphine have less potentials to influence on bowel function , dependence and addiction because of a less euphoric effect. And these opioids are stronger analgesics than morphine at the same dose. Four patients had nausea and/or vomiting after oral administration of pentazocine. They had buprenorphine (rectal suppository) after that and maintained good satisfaction in pain relief with no adverse events. These drugs were seemed to be efficient for the management of non-malignant pain of the patients, who had lower ADL and constipation,