Evidence-based review of the literature on intrathecal delivery of pain medication.

Evidence-based medicine depends on the existence of controlled clinical trials that establish the safety and efficacy of specific therapeutic techniques. Many interventions in clinical practice have achieved widespread acceptance despite little evidence to support them in the scientific literature; the critical appraisal of these interventions based on accumulating experience is a goal of medicine. To clarify the current state of knowledge concerning the use of various drugs for intraspinal infusion in pain management, an expert panel conducted a thorough review of the published literature. The exhaustive review included 5 different groups of compounds, with morphine and bupivacaine yielding the most citations in the literature. The need for additional large published controlled studies was highlighted by this review, especially for promising agents that have been shown to be safe and efficacious in recent clinical studies.

Clinical guidelines for intraspinal infusion: report of an expert panel. PolyAnalgesic Consensus Conference 2000.

Consensus guidelines developed by an expert panel are helpful to clinicians when there is variation in practice and lack of a firm evidence base for an intervention, such as intraspinal therapy for pain. An internet-based survey of practitioners revealed remarkable variation in practice patterns surrounding intraspinal therapy. This prompted an interdisciplinary panel with extensive clinical experience in intraspinal infusion therapy to evaluate the results of the survey, the systematic reviews of the literature pertaining to this approach, and their own clinical experience with long-term spinal infusions. The panel proposed a scheme for the selection of drugs and doses for intraspinal therapy, and suggested guidelines for administration that would increase the likelihood of a successful outcome. These expert panel guidelines were designed to provide an initial structure for clinical decision making that is based on the best available evidence and the perspectives of experienced clinicians.

Future directions in the management of pain by intraspinal drug delivery.

Management of pain by intraspinal delivery of drugs enables physicians to target specific sites of action. While this novel approach is gaining increasing use, well-designed studies are needed. A major limitation is the lack of published information on existing drugs used for intrathecal delivery. (The strengths and weaknesses of this information are reviewed in the accompanying literature review article.) Promising agents such as bupivacaine, hydromorphone, and morphine/clonidine combinations warrant further research in large prospective (ideally randomized and double-blind) clinical safety and efficacy studies. These studies may provide data for pain management guidelines, such as those included in the preceding paper. Research must also address issues of formulation, chemical stability/compatibility, pharmacokinetics, and toxicology during clinical development and drug approval. Finally, more basic studies and early phase trials of other potential agents for intrathecal pain management (e.g., gabapentin) are needed.

An educational implementation of a cancer pain algorithm for ambulatory care.

Algorithms are proposed as a means of operationalizing guidelines or standards for cancer pain management. Professional education is used as the means to translate knowledge into practice. Outcomes measurement is the gold standard for validating improvement. This study used an educational intervention to transfer knowledge on implementing a previously tested algorithm for cancer pain management into community outpatient oncology clinics and, subsequently, measuring patient outcomes. Physicians and nurses from 9 Puget Sound clinics were randomized by institution blocks to either "training" or "no training." Role model physician/nurse teams were the core faculty for a day-long seminar. Written reference materials and documentation tools were provided to the trained physician/nurse teams. A total of 105 patients of trained and untrained providers were accrued and assessed over 4 months. Patients of trained providers had a significant reduction in usual pain over the 4 months of data collection compared with patients of untrained providers (t = 2.0; p = .05). Improvements were modest in the prescription of opioid analgesics and dramatic in the prescription of co-analgesics for neuropathic pain. There was a clear deterioration in the impact of the training over time. The most significant effect occurred within the first 140 days after the intervention and was followed by a gradual return to baseline practice. In conclusion, algorithmic interventions can be successfully transferred into community practice, but further work must be performed to develop methods for securing retention of knowledge and maintaining improved outcomes.

Implementing guidelines for cancer pain management: results of a randomized controlled clinical trial.

PURPOSE: Pain and symptom management is an integral part of the clinical practice of oncology. A number of guidelines have been developed to assist the clinician in optimizing comfort care. We implemented clinical guidelines for cancer pain management in the community setting and evaluated whether these guidelines improved care. PATIENTS AND METHODS: Eighty-one cancer patients, aged 37 to 76 years, were enrolled onto a prospective, longitudinal, randomized controlled study from the outpatient clinic settings of 26 western Washington-area medical oncologists. A multilevel treatment algorithm based on the Agency for Health Care Policy and Research Guidelines for Cancer Pain Management was compared with standard-practice (control) pain and symptom management therapies used by community oncologists. The primary outcome of interest was pain (Brief Pain Inventory); secondary outcomes of interest were all other symptoms (Memorial Symptom Assessment Scale) and quality of life (Functional Assessment of Cancer Therapy Scale). RESULTS: Patients randomized to the pain algorithm group achieved a statistically significant reduction in usual pain intensity, measured as slope scores, when compared with standard community practice (P < .02). Concurrent chemotherapy and patient adherence to treatment were significant mediators of worst pain. There were no significant differences in other symptoms or quality of life between the two treatment groups. CONCLUSION: This guideline implementation study supports the use of algorithmic decision making in the management of cancer pain. These findings suggest that comprehensive pain assessment and evidence-based analgesic decision-making processes do enhance usual pain outcomes.

Complications of neuraxial infusion in cancer patients.

Intraspinal drug delivery systems can be effective in controlling intractable pain. However, before these invasive pain therapies are initiated and to avoid or minimize any complications associated with their use, there must be a thorough understanding of the etiology of the pain, the underlying cancer, and antineoplastic therapy. For example, the assumption that intraspinal cannulation is contraindicated in all patients with known vertebral metastatic lesions is not supported in clinical practice. A majority of spinal metastatic lesions involve the vertebral body, which is distant from the dorsal position of the intraspinal catheter. Based on extensive experience, the only pragmatic contraindications to neuraxial infusion device implantation are those also revelant to surgical intervention. Careful patient selection may help avoid some complications and constant vigilance may be the best defense against errors.

Alternative intrathecal agents for the treatment of pain.

There is a need to develop alternative agents for intrathecal pain therapy for patients who either cannot tolerate the side effects of or who no longer obtain sufficient analgesia with opioids. The experimental use of several compounds in intrathecal drug delivery is currently in progress, with the development of clonidine as the single most important advance in the improvement of pain treatment. Clonidine, an α(2) -adrenergic receptor agonist, appears to be safe and effective in the treatment of cancer and nonmalignant pain, with its effects most pronounced in patients whose pain consists of a neuropathic component. Other possible effective agents for intrathecal delivery include bupivacaine, octreotide, and SNX-111. The preclinical and clinical profiles for these promising new intrathecal pain medications are discussed.

Epidurograms in the management of patients with long-term epidural catheters.

BACKGROUND AND OBJECTIVES: Standardized test doses have been established in the practice of anesthesiology to determine the location of the epidural catheter tip. The resulting data obtained after test dosing is open to interpretation, and comparison is difficult. A more objective method of catheter verification and epidural space measurement is indicated in long-term epidural catheterization. The goal of this review is to define a standard procedure for epidurography, explore the use of an epidurogram algorithm in differential diagnosis, and review the temporal relationship of a series of epidurograms. METHODS: A standard epidurogram procedure was defined and used for the study. Routine postoperative epidurograms were obtained following epidural catheter placement. Serial epidurograms were obtained when clinically indicated, as described in the epidurogram algorithm. Radiographs taken after injection of the dye were used for determination of epidural catheter tip location and volume dye flow. Two cases are presented to demonstrate the effectiveness of the epidurogram algorithm. RESULTS: Epidurograms show dye dispersion within the space, allowing for visualization of anomalies, resulting in a permanent record for later review. Case reports demonstrate the use of epidurograms in determining the cause of changes in epidural analgesia. CONCLUSIONS: The review of repeated epidurograms and presented case reports support the use of epidurograms as a diagnostic tool for clinical practice. Abnormal epidurograms helped determine epidural space infection, tumor obstruction, space compression from vertebral compression fractures, and epidural fibrosis. The addition of a contrast computed tomographic scan after epidurography allows for more accurate diagnostic interpretation of epidural space pathology. The use of a standard epidurogram technique allows this procedure to be used in the differential diagnosis of suspected problems in the epidural space.

Ondansetron in the treatment of postoperative nausea and vomiting in ambulatory outpatients: a dose-comparative, stratified, multicentre study.

The safety and efficacy of ondansetron were evaluated in the treatment of postoperative nausea and vomiting. Five hundred patients who experienced nausea or vomiting in the Post-Anaesthesia Care Unit within the first 2 h of recovery were randomized to receive either 1, 4, or 8 mg of ondansetron, or placebo. All patients had undergone ambulatory surgery with general endotracheal anaesthesia. Episodes of emesis, nausea scores, adverse events, vital signs, and laboratory values were assessed before and during the 24 h after study drug administration. Patients were evaluated for the first 2 h in the Post-Anaesthesia Care Unit then followed up for the next 22 h. Complete response was defined as no emetic episodes, no nausea or no rescue anti-emetic medication. For the 0-24 h study period, complete response occurred in only 15% of the placebo group compared to 41%, 47%, and 47% in the 1, 4, and 8 mg ondansetron groups, respectively. Mean nausea scores (scale of 0-10) during the initial observation period (0-2 h) were significantly lower for all doses of ondansetron [2.2 (1 mg), 1.7 (4 mg), and 2.1 (8 mg)] compared to placebo (3.0). The optimal dose of ondansetron for the treatment of postoperative nausea and vomiting was found to be 4 mg. All doses of ondansetron were well tolerated. No clinically significant increases in laboratory parameters or alterations in haemodynamic stability occurred in the ondansetron groups compared to placebo.

Infection during chronic epidural catheterization: diagnosis and treatment.

A potentially serious complication of long-term epidural catheterization in cancer patients is infection. The early signs of infection were studied in 350 patients in whom long-term epidural catheters were inserted. Three areas of the catheter track were found to be involved; exit site and superficial catheter track infection, and epidural space infection. The authors identified the early signs of infection in each area and the progress of the infection from the deep track to include the epidural space in four of these patients. All 19 patients who developed deep track or epidural infections were successfully treated with antibiotics and catheter removal. None of the patients required surgery for spinal cord decompression. Catheters were replaced in 15 of the 19 treated patients who requested them after treatment with no recurrent infections. It was concluded that use of long-term epidural catheterization is associated with a definable epidural infection rate. The use of epidural opioid analgesia is an effective and safe means of obtaining pain relief for terminally ill patients when patients are monitored for possible infection and receive prompt treatment when the diagnosis is established.