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PubMed1983

Relief of continuous chronic pain by intraspinal narcotics infusion via an implanted reservoir.

Ten patients with intractable pain (five cancer and five nonmalignant) were treated with continuous intraspinal morphine delivered by an implanted continuous infusion system. Both patient groups were evaluated and compared using an identical battery of psychometric examinations administered before and 12 weeks after therapy. The cancer-pain group reported significant reduction in pain on serial visual pain analogue scales at 12 weeks compared with no change in the nonmalignant-pain group reports despite a much lower baseline report in the cancer group. Both groups of patients reduced their oral narcotic requirement significantly during continuous intraspinal morphine infusion. While the cancer patients took more oral narcotic at baseline, at 12 weeks no difference existed in oral intake between the two groups. Both groups required significant serial increases in infused morphine, indicating that spinal opiate receptor tolerance occurs. The results of this study confirm the sustained analgesic efficacy reported earlier in cancer-related pain syndromes, thus supporting further cautious expansion of this therapy within the cancer-related pain population. In contrast, a poor response was seen in the nonmalignant-pain group, consistent with the unsatisfactory responses to many potentially analgetic approaches to chronic nonmalignant pain. We are thus discouraged from further use of this therapy in the patient with chronic nonmalignant pain.

Administration, Oral↗
PubMed1996

[Reconstructive and non-reconstructive procedures in the treatment of the threatened limb].

Limb threatening ischemia is an acute step in the chronic course of peripheral arterial obstructive disease that requires some form of intervention. The objective of this study is to prove that reconstructive surgery as well as non reconstructive approaches are associated with positive results. Ours is a retrospective analysis of a ten year experience in the treatment of limb threatening ischemia. In the period 1983-93, 139 patients under-went 164 procedures. 67% of patients were diabetics. Early in the observation period the therapeutic strategy was non reconstructive, the procedure of choice was sympathectomy. Later vascular reconstructions have been recognized as the procedures of choice. In the cases not amenable to reconstructive procedures according to our group criteria (absence of a tibial vessel in continuity with a patent pedal arch), we have employed procedures such as prostanoid infusion; thrombolysis and epidural spinal cord stimulation. Reconstructive procedures have been associated with a decrease in the number of major amputations. Alternative procedures, employed in patients not amenable to reconstruction have proven worthwhile in terms of limb salvage even if this trend is limited to a short period of observation.

Arterial Occlusive Diseases↗
PubMed1998

Regional analgesia in labour: a new look.

Regional analgesia for labour is popular, controversial and its safe provision complex. With the introduction of opiate/local anaesthetic mixtures, new infusion pumps and atraumatic spinal needles this form of anaesthesia has changed radically over the past decade.

Analgesia, Epidural↗
PubMed2001

Pegylated brain-derived neurotrophic factor shows improved distribution into the spinal cord and stimulates locomotor activity and morphological changes after injury.

The neurotrophin brain-derived neurotrophic factor (BDNF) shows promise for the treatment of central nervous system (CNS) trauma and disease. Effective delivery methods are required, however, for BDNF to be useful as a therapeutic agent. To this end, we examined the penetration of intrathecally infused N-terminal pegylated BDNF (peg-BDNF) compared to similar infusion of native BDNF after spinal cord injury (SCI). Pegylation dramatically improved delivery of BDNF to the spinal cord and induced the expression of Fos in spinal cord neurons. To test whether enhanced delivery would improve the modest effects on behavioral recovery and axonal outgrowth observed with native BDNF infusion, we assessed the efficacy of 2-week 25 microg/day peg-BDNF treatment, beginning 12-24 h (early) or 15 days (delayed) after midthoracic spinal contusion. Similar to native BDNF, early treatment with peg-BDNF accelerated the recovery of stepping in the open-field and acutely stimulated locomotor central pattern generator activity, as seen by the activation of hindlimb airstepping during either period of administration. The infusion of peg-BDNF, regardless of the timing of delivery, was related to enhanced sprouting of putative cholinergic fibers, like that observed after high dose native BDNF treatment. Despite improved delivery, however, neither axonal responses nor the extent of locomotor recovery were enhanced compared to native BDNF treatment. This suggests that alternative strategies, such as neurotrophin treatment in conjunction with cell transplantation techniques, or treatment nearer the cell bodies of target neurons might be employed in an attempt to effect significant repair after SCI.

Animals↗
PubMed2006

Ketorolac prevents recurrent withdrawal induced hyperalgesia but does not inhibit tolerance to spinal morphine in the rat.

Chronic use of opioid is associated with pro-nociceptive phenomena such as hyperalgesia or tolerance. The interaction between opioid and non-steroidal anti-inflammatory drugs (NSAIDs) with respect to opioid-associated hyperalgesia and tolerance remains largely unknown. This study examines the effect of subcutaneous or intrathecal administration of ketorolac, an NSAID, on recurrent withdrawal induced hyperalgesia and tolerance to spinal morphine in rats. Animals were infused with morphine intrathecally, and daily subcutaneous naloxone was used for recurrent withdrawal purpose. We observed that escape latencies on hot box were decreased in animals subjected to withdrawal, and this decrease was reversed by subcutaneous ketorolac pretreatment. In addition, we observed that recurrent withdrawal did not significantly affect the magnitude of spinal morphine tolerance. Compared to controls, all morphine infused animals showed similar changes in their dose responses to spinal morphine, effective dose 50 values and tolerance ratios; and these changes were not affected by the ketorolac given subcutaneously. The effect of ketorolac on tolerance was further examined by directly delivering ketorolac to the spinal cord, and again we observed similar changes in the daily latency, percentage of area under the curve and percentage of maximal possible effects among groups infused with morphine, regardless of intrathecal ketorolac treatment. Together, our results demonstrate that recurrent withdrawal is associated with hyperalgesia but this has no effect on the tolerance development; ketorolac protects against recurrent withdrawal induced hyperalgesia without significantly altering spinal morphine tolerance.

Analgesics, Opioid↗
PubMed1990

Spinal opioids in the home and hospice setting.

The outpatient management of spinal opioids presents multiple challenges to the home infusion pharmacist. These include compounding, Schedule II prescription control, dispensing for long-term infusion or injection, reimbursement, and the management of opioids in the home. Although spinal opioids such as meperidine, fentanyl, and methadone have been used to control intractable pain, preservative-free morphine is the preferred opioid for epidural and intrathecal injection. Commercial products, including Astromorph (Astra) and Duramorph (Elkins Sinn), are available but relatively expensive when compared with morphine prepared in the pharmacy or morphine with preservatives. Local anesthetics, including bupivacaine, have been combined with preservative-free morphine in the home setting. Spinal opioids can be administered intermittently, by continuous infusion, or patient-controlled analgesia pump. Extensive clinical experience indicates that the home administration of spinal opioids is safe and effective. There is a need for additional research on stability, storage and use of various opioids administered in the home environment.

Analgesia, Epidural↗
PubMed1991

Control of cancer pain by epidural infusion of morphine.

Pain that cannot be controlled by traditional oral and parenteral methods in those patients with advanced cancer can be alleviated by spinal administration of narcotics. Epidural and intrathecal infusion with morphine causes analgesia by blocking spinal receptors without significant long-term central nervous, gastrointestinal, and genitourinary system effects. Of the total of 33 patients, epidural catheters inserted in 20 patients then connected by a subcutaneous tunnel to a continuous infusion system. Implanted pumps were used in each of these patients. Because of the cost and limitations of the implanted pumps, epidural catheters were connected, either directly or by subcutaneous reservoirs, to external ambulatory infusion pumps in the remaining 13 patients. Patient assessment by a linear analogue scale to measure pain levels determined that 23 of the 33 total patients (70%) had excellent or good relief of pain. The delivery of spinal administration of narcotics to treat intractable cancer pain in patients is safe. Most importantly, this method of delivery can be used in community hospitals, in outpatient settings, and in home health care programs.

Adult↗
PubMed2005

The effects of ketorolac injected via patient controlled analgesia postoperatively on spinal fusion.

Lumbar spinal fusions have been performed for spinal stability, pain relief and improved function in spinal stenosis, scoliosis, spinal fractures, infectious conditions and other lumbar spinal problems. The success of lumbar spinal fusion depends on multifactors, such as types of bone graft materials, levels and numbers of fusion, spinal instrumentation, electrical stimulation, smoking and some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January 2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal stenosis or spondylolisthesis, were retrospectively enrolled in this study. One surgeon performed all 88 posterolateral spinal fusions with instrumentation and autoiliac bone graft. The patients were divided into two groups. The first group (n=30) was infused with ketorolac and fentanyl intravenously via patient controlled analgesia (PCA) postoperatively and the second group (n=58) was infused only with fentanyl. The spinal fusion rates and clinical outcomes of the two groups were compared. The incidence of incomplete union or nonunion was much higher in the ketorolac group, and the relative risk was approximately 6 times higher than control group (odds ratio: 5.64). The clinical outcomes, which were checked at least 1 year after surgery, showed strong correlations with the spinal fusion status. The control group (93.1%) showed significantly better clinical results than the ketorolac group (77.6%). Smoking had no effect on the spinal fusion outcome in this study. Even though the use of ketorolac after spinal fusion can reduce the need for morphine, thereby decreasing morphine related complications, ketorolac used via PCA at the immediate postoperative state inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs such as ketorolac, should be avoided after posterolateral spinal fusion.

Adult↗
PubMed2005

Infusion of neostigmine-glycopyrrolate for bowel evacuation in persons with spinal cord injury.

Defecatory complications are common after spinal cord injury (SCI) and have been attributed, in part, to an imbalance of the autonomic nervous system between parasympathetic and sympathetic effects on the colon. Because parasympathetic (i.e., cholinergic) input to the bowel may be downregulated after SCI, it was hypothesized that neostigmine, a medication that increases cholinergic tone by blocking the metabolism of acetylcholine, might promote bowel evacuation in these persons. Since neostigmine is known to cause bradycardia and bronchoconstriction, we also assessed whether these side-effects could be prevented by coadministration of neostigmine with glycopyrrolate, an anticholinergic agent that has limited activity on the muscarinic receptors of the colon. The hypothesis was tested in 13 persons with SCI in whom videofluoroscopy was carried out after instillation of a barium oatmeal paste into the rectum and descending colon. On separate days, subjects received, in a randomized, blinded design, one of three intravenous infusates (normal saline, 2 mg neostigmine, or 2 mg neostigmine + 0.4 mg glycopyrrolate). The effect of these infusates on bowel evacuation of the barium paste, heart rate, and airway resistance was determined. Both neostigmine and neostigmine + glycopyrrolate resulted in prompt bowel evacuation. The nadir heart rate was lower after neostigmine alone than with the combination. Neostigmine administration increased both total and central airway resistance, an effect that was not observed with the coadministration of glycopyrrolate. Other side-effects of neostigmine and the combination of drugs included muscle fasciculations and dry mouth, both of which were mild and short-lived. Abdominal cramping was noted in subjects with spinal cord lesions below thoracic level 10. These results indicated that neostigmine/glycopyrrolate administration is safe and well tolerated in persons with chronic SCI.

Adult↗
PubMed2000

Neutralizing antibodies against neurite growth inhibitor NI-35/250 do not promote regeneration of sensory axons in the adult rat spinal cord.

Neutralization of the myelin-associated neurite growth inhibitors NI-35 and NI-250 by IN-1 antibodies can promote axonal regeneration of several types of central nervous neurons. Here, we investigated in adult rats whether IN-1 can promote regeneration of ascending sensory axons across a peripheral nerve bridge back into the spinal cord. IN-1 was administered by hybridoma cells injected in the cerebral cortex or thoracic cord, its presence confirmed in tissue sections and cerebrospinal fluid, and its effectiveness demonstrated in co-cultures of oligodendrocytes and sensory neurons. With a two week infusion of control vehicle into the dorsal spinal cord 3 mm rostral to the nerve graft, only 3+/-2% of the anterogradely labeled sensory fibers present at the rostral end of the nerve graft had grown up to 0.5 mm, but not farther into the spinal cord. A similar limited extent of regeneration was seen with IN-1 or with infusion of Dantrolene, an inhibitor of NI-35/250 activity in vitro. With infusion of nerve growth factor rostral to the nerve graft, 40% of the fibers at the rostral end of the graft were found at 0.5 mm, 34% at 1 mm, 24% at 2 mm and 14% at 3 mm (the infusion site) into the spinal cord. Treatment with IN-l antibodies did not enhance the growth-promoting effects of nerve growth factor. We suggest that the neurite growth inhibitors NI-35 or NI-250 do not play a major inhibitory role in the regeneration of the ascending sensory fibers across a nerve bridge and back into the spinal cord of the adult rat.

Animals↗
PubMed1993

Intrathecal baclofen for spinal spasticity: implications for nursing practice.

Treating severe spasticity with the continuous infusion of intrathecal baclofen through an implantable delivery system is a new and successful alternative to oral medications and ablative surgical procedures. Nurses have a vital role in patient care throughout all phases of therapy. Advances in this technology hold promise for our future in treating other neurologic disorders.

Baclofen↗
PubMed2006

Propofol and tourniquet induced ischaemia reperfusion injury in lower extremity operations.

BACKGROUND AND OBJECTIVE: Extremity surgery with tourniquet to provide a bloodless field may be a good human model for ischaemia reperfusion (IR) injury. The aim of this study was to investigate the effects of three different modes of propofol use on tourniquet induced IR injury in lower extremity operations. METHODS: Thirty-three consecutive ASA Grade I and II patients were randomized into three groups of 11 patients each. In the spinal group (Group S), after intrathecal anaesthesia, sedation was given with a propofol infusion at 2 mg kg-1 h-1 after a 0.2 mg kg-1 bolus dose and fentanyl 100 microg. In the general (Group G) and TIVA (Group T) groups, general anaesthesia was induced with propofol 2 mg kg-1 with fentanyl 100 microg and maintained with inhalation of halothane or infusion of propofol respectively. Venous blood samples were obtained at different time points for measurements of plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels. RESULTS: Plasma MDA levels were increased significantly in the Group G at 1 min before tourniquet release and 5 and 20 min after tourniquet release compared with before induction of general anaesthesia (baseline). Before intrathecal anaesthesia and before induction of general anaesthesia significantly decreased levels of MDA were observed both before and after tourniquet release compared to baseline. Plasma SOD and CAT concentrations were decreased significantly only at tourniquet release in the Group G compared with baseline. In the Groups S and T these enzymes were not changed significantly. Plasma GPx levels were not altered in any groups. CONCLUSION: Propofol administration may inhibit lipid peroxidation and restore antioxidant enzyme levels in extremity surgery requiring tourniquet application.

Adult↗
PubMed2002

Attenuation of morphine tolerance after antisense oligonucleotide knock-down of spinal mGluR1.

1. Chronic systemic treatment of rats with morphine leads to the development of opioid tolerance. This study was designed to examine the effects of intrathecal (i.t.) infusion of a metabotropic glutamate receptor 1 (mGluR1) antisense oligonucleotide, concomitant with chronic morphine treatment, on the development of tolerance to morphine's antinociceptive effects. 2. All rats received chronic (6 day) s.c. administration of morphine to induce opioid tolerance. Additionally, rats were treated with either mGluR1 antisense (AS), missense (MIS) or artificial cerebrospinal fluid (ACSF) by i.t. infusion via chronically implanted i.t. catheters connected to osmotic mini-pumps. The effects of acute i.t. or s.c. morphine on tail-flick latencies were assessed prior to and following chronic s.c. morphine treatment for all chronic i.t. infusion groups. mGluR1 protein level in the spinal cord was determined by Western blot analysis for all treatments, assessing the efficiency of knock-down with AS treatment. 3. Acute i.t. morphine dose-dependently produced antinociception in the tail-flick test in naïve rats. Systemic morphine-treated rats administered i.t. ACSF or MIS developed tolerance to i.t. morphine. Chronic i.t. infusion with mGluR1 AS significantly reduced the development of tolerance to i.t. morphine. 4. In contrast to i.t. morphine, tolerance developed to the antinociceptive effects of s.c. morphine, in all i.t. infusion groups, including the mGluR1 AS group. 5. The spinal mGluR1 protein level was dramatically decreased after mGluR1 AS infusion when compared to control animals (naïve and ACSF-treated animals). 6. These findings suggest that the spinal mGluR1 is involved in the development of tolerance to the antinociceptive effects of morphine. Selective blockade of mGluR1 may be beneficial in preventing the development of opioid analgesic tolerance.

Analgesics, Opioid↗
PubMed1990

Long-term pain relief produced by intrathecal morphine infusion in 53 patients.

The present report details the characteristics of the analgesic effects of morphine administered chronically by infusion pumps implanted in 53 patients suffering from terminal metastatic disease. The median postimplant survival time in these patients was 4 months. Patients (mean age 58 years) were characterized according to the duration of pain before pump implantation (mean 16 months), prior consumption of systemic opioids (mean one to six daily analgesic equivalents of morphine), and their response to a trial intrathecal dose of morphine (1 to 2 mg). The median infusion dose at 2 weeks was 3.8 mg/day. The analgesic index, calculated as (quality of pain relief x duration of pain relief in hours)/morphine dose in mg, that was observed after the trial dose of morphine was determined for each patient. A close correlation was observed between the acute (2-week) infusion dose necessary to produce pain relief and the analgesic index such that the infusion dose = -8.0 x log (analgesic index) + 17.1. By 16 weeks, the mean spinal morphine dose for the group had increased by a factor of about 2.5; however, significant variation in the dose incrementation was documented. The maximum increase was observed in patients with a low analgesic index, and this rapid incrementation was usually correlated with an unsatisfactory overall outcome. Evidence that long-term infusion continues to yield analgesia was evidenced in six cases where there was an unanticipated loss of drug infusion and a corresponding increase in parenteral narcotic consumption. These data indicate the long-term efficacy and safety of spinal opioid infusion in patients with terminal cancer, and emphasize the advantage of assessing the sensitivity of the patient to spinal opioids by a standardized trial injection prior to pump placement as a prognostic indication of outcome.

Adult↗
PubMed1979

Pentolinium for control of reflex hypertension in spinal cord injured patients.

Ganglioplegia was produced by intravenous infusion of pentolinium tartrate 5 mg to control reflex hypertension in 29 patients with chronic spinal cord injuries undergoing 32 elective surgical procedures. The patient group with lesions above the first thoracic segment (T1) demonstrated significant but moderate intraoperative elevation of both systolic and diastolic pressure whether pentolinium was given prior to or during surgical stimulation. Patients with lesions below T1 had no significant pressure elevations with either mode of therapy. Pentolinium ganglioplegia can safely maintain blood pressure within reasonable limits in these patients; some increase in dosage may be required in patients with lesions above T1.

Adolescent↗
PubMed2004

[Morphological and functional changes in spinal ganglion neurons after epidural clopheline administration].

The aim of this chronic experimental study performed in 16 dogs was to determine the effect of epidural infusion of 0.01% clopheline solution on the morphological and histoenzymological characteristics of spinal ganglion neurons. Daily infusions of clopheline at the dose of 15 mg/kg for 14 days caused a decrease in capillary permeability in the spinal ganglia at the injection site and its increase in the intact areas. This finding suggests the changes in the activity of the microcirculatory bed with a disturbed interaction in capillary-neuron system. Analysis of morphometric parameters has demonstrated the presence of some functional and reversible dystrophic changes in spinal ganglion neurons, which were associated with epidural infusion of both clopheline and isotonic solution of sodium chloride. Determination of the activity of oxidation-reduction enzymes, which reflect the course of aerobic and anaerobic processes in spinal ganglion neurons, has shown no significant differences between the groups of animals infused with or isotonic solution of sodium chloride. In conditions of chronic experiment no significant variations were found in RNA content in ganglionic cells at and outside the sites of infusion of clopheline and of isotonic solution of sodium chloride.

Analgesics↗
PubMed1989

Intrathecal baclofen for severe spinal spasticity.

We studied the effect of the intrathecal infusion of baclofen, an agonist of gamma-aminobutyric acid, on abnormal muscle tone and spasms associated with spinal spasticity, in a randomized double-blind crossover study. Twenty patients with spinal spasticity caused by multiple sclerosis or spinal-cord injury who had had no response to treatment with oral baclofen received an intrathecal infusion of baclofen or saline for three days. The infusions were administered by means of a programmable pump implanted in the lumbar subarachnoid space. Muscle tone decreased in all 20 patients (mean [+/- SD] Ashworth score for rigidity, from 4.0 +/- 1.0 to 1.2 +/- 0.4; P less than 0.0001), and spasms were decreased in 18 of the 19 patients who had spasms (mean [+/- SD] score for spasm frequency, from 3.3 +/- 1.2 to 0.4 +/- 0.8; P less than 0.0005). Tests for motor function, neurologic examination, and assessments by the patients correctly indicated when baclofen was being infused in all cases. All patients were then entered in an open long-term trial of continuous infusion of intrathecal baclofen. During a mean follow-up period of 19.2 months (range, 10 to 33), muscle tone has been maintained within the normal range (mean Ashworth score, 1.0 +/- 0.1) and spasms have been reduced to a level that does not interfere with activities of daily living (mean spasm score, 0.3 +/- 0.6). No drowsiness or confusion occurred, one pump failed, and two catheters became dislodged and had to be replaced. No infections were observed. Our observations suggest that intrathecal baclofen is an effective long-term treatment for spinal spasticity that has not responded to oral baclofen.

Adult↗