An appraisal of the ethical issues involved in high-technology cancer pain relief.

...We will turn our attention to the current state of pain relief technology and the ethical questions surrounding the use of advanced technology, otherwise referred to as "high-tech," pain relief. It is obvious that pain may decrease the quality of life for cancer patients. The availability of long-acting narcotics, such as MS Contin or methadone, affords cancer patients long-duration pain relief at minimal cost. The use of adjuvant medications may also be important. Clinical examples of the effective use of adjuvant medications include the addition of a nonsteroidal, anti-inflammatory agent to help patients cope with bone pain and the use of a serotonin blocking agent to reduce the transmission of pain impulses in the spinal cord. Only a small percentage of patients are good candidates for high-tech delivery systems for narcotic administration. In our pain management clinic, all patients are initially placed on oral medications. When the side effects of oral medications become excessive, or the patient becomes unable to take oral medications, high-tech modalities are considered for use.

Thalamic field potentials in chronic central pain treated by periventricular gray stimulation -- a series of eight cases.

Chronic deep brain stimulation (DBS) of the periventricular gray (PVG) has been used for the treatment of chronic central pain for decades. In recent years motor cortex stimulation (MCS) has largely supplanted DBS in the surgical management of intractable neuropathic pain of central origin. However, MCS provides satisfactory pain relief in about 50-75% of cases, a range comparable to that reported for DBS (none of the reports are in placebo-controlled studies and hence the further need for caution in evaluating and comparing these results). Our experience also suggests that there is still a role for DBS in the control of central pain. Here we present a series of eight consecutive cases of intractable chronic pain of central origin treated with PVG DBS with an average follow-up of 9 months.In each case, two electrodes were implanted in the PVG and the ventroposterolateral thalamic nucleus, respectively, under guidance of corneal topography/magnetic resonance imaging image fusion. The PVG was stimulated in the frequency range of 2-100 Hz in alert patients while pain was assessed using the McGill-Melzack visual analogue scale. In addition, local field potentials (FPs) were recorded from the sensory thalamus during PVG stimulation.Maximum pain relief was obtained with 5-35 Hz stimulation while 50-100 Hz made the pain worse. This suggests that pain suppression was frequency dependent. Interestingly, we detected low frequency thalamic FPs at 0.2-0.4 Hz closely associated with the pain. During 5-35 Hz PVG stimulation the amplitude of this potential was significantly reduced and this was associated with marked pain relief. At the higher frequencies (50-100 Hz), however, there was no reduction in the FPs and no pain suppression.We have found an interesting and consistent correlation between thalamic electrical activity and chronic pain. This low frequency potential may provide an objective index for quantifying chronic pain, and may hold further clues to the mechanism of action of PVG stimulation. It may be possible to use the presence of these slow FPs and the effect of trial PVG DBS on both the clinical status and the FPs to predict the probable success of future pain control in individual patients.

Unresectable and locally recurrent rectal cancer treated with radiotherapy or bilateral internal iliac artery infusion of 5-fluorouracil.

Seventy-nine patients with histopathologically verified unresectable or locally recurrent rectal cancer were nonrandomly allocated to radiotherapy or regional intra-arterial infusion of 5-Fluorouracil (5-FU). Fifteen patients with unresectable and 32 with locally recurrent rectal cancer were subjected to radiotherapy. The absorbed dose was 30 Gy in patients with an unresectable tumor and 45 Gy in patients with locally recurrent rectal cancer. Six patients with unresectable and 26 with locally recurrent rectal cancer received bilateral internal iliac artery infusion of 5-FU in a median dose of 7.5 g. There was no difference in survival between the two methods of treatment. Resection of an initially unresectable tumor could be performed in 5 of 21 patients (4 after radiotherapy and 1 after chemotherapy). All except eight patients had pelvic or perineal pain before treatment. Forty of 43 (93%) patients reported pain relief after radiotherapy and 21 of 28 (75%) after infusion therapy. Ten nonresponders were subjected to alternative treatment (three to intra-arterial infusion and seven to radiotherapy). Five of these ten patients reported complete pain relief and five partial pain relief. After radiotherapy, no significant side effects or complications were observed. The infusion chemotherapy was the cause of death in one patient. In summary, similar palliation was achieved with bilateral iliac artery 5-FU-infusion and radiotherapy. Owing to the complications registered with infusion therapy, radiotherapy must be considered the treatment of choice for these patients. Patients who do not respond to radiotherapy or suffer recurrence of pelvic and perineal pain may receive further palliation from intra-arterial infusion.

Postoperative pain relief by epidural morphine.

Postoperative pain relief was studied in 280 patients undergoing various kinds of surgery, e.g., thoracic, upper and lower abdominal, perineal, obstetric, and orthopedic. Morphine, 2 or 4 mg, was given after surgery through an indwelling epidural catheter. Excellent analgesia was noted in 87% of patients; only 3.5% of patients were dissatisfied. A single injection gave complete pain relief for the entire postoperative period in 30% of cases; in the remaining patients the mean duration of analgesia was 10.7 hours (SD +/- 4.3). Plasma morphine concentrations recorded after 2-mg doses suggest a regional spinal action as the basis for the long duration of analgesia, although the initial effect after 4-mg doses might well include systemic responses due to rapid vascular uptake of morphine from the epidural space. Peak expiratory flow (PEF) measurements and arterial blood gas analyses showed no significant early postoperative respiratory depression. Absence of sedation, orthostatic hypotension, respiratory depression, and motor paralysis facilitated early ambulation with less risk for postoperative respiratory complications. It is concluded that 2-mg doses of epidural morphine give good analgesia of long duration despite low plasma levels. After upper abdominal and thoracic surgery higher doses (4 mg) may be necessary in healthy patients. Elderly and frail patients appear to be sensitive to epidural morphine and doses in excess of 2 mg should be avoided regardless of the type of surgery. With this dose schedule we have not encountered delayed respiratory depression.

Autologous islet transplantation to prevent diabetes after pancreatic resection.

BACKGROUND: Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. OBJECTIVE: Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. PATIENTS AND METHODS: Of the 48 patients, 43 underwent total or near-total (> 95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. RESULTS: One perioperative death occurred. Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received > 300,000 islets, 74% were insulin independent at > 2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = -0.52, p = 0.006) and the dispersion method (p = 0.005). CONCLUSION: Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.

pain relief mediated by implantable drug delivery devices.

Various totally implantable drug delivery systems from single access ports to micropumps are now available for administration of repeated boluses, and continuous or programmable infusions. In this respect, emphasis is given to a relatively cheap, totally implantable system for self-administering intraspinal opiates in the treatment of cancer pain. The SECOR pump system, developed by Cordis, consists of a dual pump with refill port and safety valve. The volume of the pliable reservoir is 12 ml and refill is accomplished with a 25-G needle. The bolus delivered with each transcutaneous activation of the pumps is 0.1 ml. Clinical results demonstrated that this patient-controlled drug delivery system is safe and provides excellent pain relief associated with terminal cancer. A possible advantage of this drug delivery system over continuous infusion pumps is that patients can elect to have the morphine delivered only when they feel pain. Thus pain relief would be maximized and tolerance build-up would be minimized.

A preliminary list to identify attitudes toward different conditions for discussing possible termination or refusal of medical treatment except for pain relief.

Effective communication about decisions concerning termination or refusal of medical treatment except for pain relief necessitates clarifying the attitudes of those in the decision-making process. Effective communication increases the likelihood that a patient's advance directives are implemented and decreases the likelihood of litigation. Psychotherapists, counselors, chaplains, etc. can be facilitators of effective communication. This study generated a list for use in discussion by asking persons who cared for individuals with terminal illnesses, critical injuries or elderly people what conditions seemed appropriate for termination or refusal of medical treatment except for pain relief. The 182 out of 204 individuals who contributed conditions showed clear agreement on terminal illnesses, brain disorders, dependence on machines for life, and other irreversible deterioration or severe loss of quality of life, lack of suitable treatment, patient's wish, and concern about the effect of the patient's condition on others. Some specified further qualifications, such as at what point during a terminal illness termination or refusal was appropriate. The list with notes could be appended to a Living Will or a Durable Power of Attorney for Health Care. The notes should be updated periodically. Through use and research, the list also can be refined further.

Long-term pain relief during spinal cord stimulation. The effect of patient selection.

We reviewed our experience with spinal cord stimulation (SCS) in treating 116 patients with pain in one or both legs. All these patients were selected for an initial week of trial stimulation by the criteria: pain due to a known benign organic cause, failure of conventional pain control methods and absence of major personality disorders. Selected patients included 78 with the Failed Back Surgery Syndrome (FBSS), in whom proven correlation existed between the clinical picture and the neuroradiological and electromyogram abnormalities. Eighty-four out of 116 selected patients underwent definitive SCS implantation after 1 week of trial stimulation with excellent results (more than 75% pain relief). They were followed clinically every 3 months for a mean follow-up period of 47 months. Forty-five patients (54%) continued to experience at least 50% of pain relief at the latest follow up. Seventy-seven patients (91%) were able to reduce their medication intake and 50 patients (60%) reported an improvement in lifestyle. FBSS patients responded more positively to the trial stimulation than the other patients. However, the later outcome was not affected by patient selection as long-term benefit was similar in all definitive SCS patients irrespective of aetiology.

Value of bone scan imaging in predicting pain relief from percutaneous vertebroplasty in osteoporotic vertebral fractures.

BACKGROUND AND PURPOSE: Patient selection for percutaneous vertebroplasty is often complicated by the presence of multiple fractures or non-localizing pain. Our purpose was to determine whether increased activity revealed by bone scan imaging is predictive of a positive clinical response to percutaneous vertebroplasty. METHODS: A retrospective chart review conducted at our institution yielded 28 vertebroplasty treatment sessions that had been performed after obtaining bone scan imaging for painful, osteoporotic compression fractures in 27 patients. Thirty-five compression fractures were treated during these 28 treatment sessions. In all cases, increased activity was revealed by bone scan imaging before treatment with vertebroplasty. Positive outcome was defined as subjective decrease in pain severity and/or increased level of patient mobility. RESULTS: Subjective pain relief was noted in 26 (93%) of 28 treatment sessions. In 14 (100%) of 14 cases with quantifiable pain levels, pain improved at least 3 points on a 10-point scale (range of improvement, 3-10 points; mean improvement, 7.4 points). Among the remaining 14 treatment sessions in which patients were unable or unwilling to quantify pain severity, the pain relief was described as complete or excellent pain relief in 11 (78%) of 14 cases. In 14 (100%) of 14 cases for which semiquantitative assessment of mobility was available, mobility improved at least one level (5-point graded scale; range of improvement, 1-4 points; mean improvement, 1.7 points). CONCLUSIONS: Increased activity revealed by bone scan imaging is highly predictive of positive clinical response to percutaneous vertebroplasty.

Intrathecal morphine in younger patients for postoperative pain following spinal fusion.

Intrathecal morphine in an average dose of 0.01 mg/kg was given to 33 patients between ages 11 and 16 years who had spinal arthrodesis for idiopathic scoliosis. The morphine was administered intrathecally as a 10 cc bolus at the conclusion of the arthrodesis, but before closure. The goal was to study safety in terms of respiratory depression and pain relief. Respirations occurred spontaneously in 30 of the 33 patients within 15 minutes of cessation of anesthesia. Respiratory depression occurred in five patients, four of whom had arterial blood pCO2 levels greater than 60 mm Hg. Thirty-one patients had relief of pain for 8 to greater than 40 hours, averaging 18 hours. Two patients had no noticeable pain relief. There appeared to be no relation between dose and pain relief in this limited dose range. We were unable to duplicate the long duration of pain relief reported elsewhere. We also were unable to decrease the side effects of respiratory depression and nausea to a level reported by others. It may be that the 10 cc bolus injected intrathecally circulates to the brain and ventricles faster than desired, or that factors relating to type of anesthesia or dose need to be considered. Low-dose intrathecal morphine does provide noticeable pain relief in younger patients undergoing spinal fusion. The side effects of nausea and respiratory depression can be managed safely with medication.