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PubMed1991

Spinal cord compression complicating subarachnoid infusion of morphine: case report and laboratory experience.

The intraspinal administration of morphine has been employed increasingly in the management of intractable pain of malignant as well as benign origin. We have encountered a previously unreported clinical complication: spinal cord compression by an inflammatory tissue mass surrounding a subarachnoid infusion catheter administering morphine, leading to paraplegia. The patient was referred to our institution after catheter and pump implantation for chronic, intractable pain associated with pre-existing lumbar arachnoid fibrosis, after multiple myelograms and surgeries. The patient may, therefore, have had an underlying propensity to foreign body reactions. We have encountered a similar phenomenon, however, in a canine laboratory model. The pathological features in both our patient and our laboratory preparation, with inflammatory tissue masses around the tip of the catheter but not around proximal subarachnoid segments, suggest an effect related to infusion, as opposed to infection or the presence of the catheter. We review the pathological features in both settings and the pertinent literature.

Adult↗
PubMed1997

[Continuous epidural morphine for postoperative pain relief after spinal surgery--use of an epidural catheter placed at the time of surgery].

Postoperative analgesia by continuous epidural morphine infusion after spinal surgery was investigated in a retrospective study. An epidural catheter was placed by surgeons at the time of surgery. Postoperative pain was less intense and use of analgesics and sedative was less frequent in patients with continuous epidural morphine (n = 41) as compared with patients without continuous epidural morphine (n = 41). Among the patients with continuous epidural morphine, postoperative pain in patients (n = 16) with the dura opened or dural rent during surgery was less intense and the uses of analgesics and sedative was less frequent as compared with patients (n = 25) without the dural rent. There were no severe complications except for respiratory depression in a patient with chronic obstructive pulmonary disease. Our study demonstrated the ease of insertion of an epidural catheter at the time of surgery and the good quality of epidural analgesia after spinal surgery.

Adult↗
PubMedDate not supplied

Hemodynamic profiles of methoxamine and B-HT 933 in spinalized ganglion-blocked dogs.

The hemodynamic profiles of methoxamine and B-HT 933 during a stepwise-increased infusion in spinalized ganglion-blocked dogs show that both compounds induce a dose-dependent increase in arterial blood pressure due to an increase in total peripheral resistance. Methoxamine initially also increases cardiac output, which contributes to the increase in blood pressure. The increased cardiac output is the result of an increased stroke volume, because heart rate is unchanged. B-HT 933 increases neither cardiac output nor heart rate. Because neither compound stimulates the heart directly, the increase in stroke volume induced by methoxamine can be due only to an increased venous return. B-HT 933 appears to be devoid of an effect on the capacitance vessels, because stroke volume and cardiac output are unchanged. The present study suggests that under in vivo conditions, postjunctional alpha 2-adrenoceptors in the capacitance vessels of the dog are not functional.

Adrenergic alpha-Agonists↗
PubMed1993

Spinal cord perfusion pressure in dogs after control of proximal aortic hypertension during thoracic aortic cross-clamping with esmolol or sodium nitroprusside.

BACKGROUND: Spinal cord perfusion pressure may be reduced when sodium nitroprusside is used to control proximal aortic hypertension during thoracic aortic clamping. The effect of esmolol infusion on spinal cord perfusion pressure during thoracic aortic clamping is unknown. This study compares spinal cord perfusion pressure following control of proximal hypertension with either sodium nitroprusside or esmolol during thoracic aortic clamping. METHODS: The thoracic aorta was cross-clamped for 30 min in 18 dogs anesthetized with halothane. A control group (n = 6) received no treatment of proximal hypertension during cross-clamping. In two other groups, proximal arterial pressure was controlled (100 mmHg) by infusion of either sodium nitroprusside (n = 6) or esmolol (n = 6). Brachial and femoral arterial pressures, spinal cord perfusion pressure, pulmonary artery occlusion, central venous pressures, and cardiac output were monitored. Neurologic assessment was performed 24 h following surgery. RESULTS: Femoral arterial pressure was lower with nitroprusside (14 +/- 3 mmHg) compared to esmolol (24 +/- 4 mmHg) after 15 min of aortic cross-clamping. Cerebrospinal fluid pressure increased during aortic cross-clamping in the sodium nitroprusside group (from 7 +/- 5 to 16 +/- 6 mmHg) but not in esmolol or control groups. Spinal cord perfusion pressure was lower with nitroprusside at 15 min of aortic cross-clamping (2 +/- 4 mmHg) compared to control (15 +/- 7 mmHg) and esmolol groups (17 +/- 11 mmHg). Esmolol infusion reduced cardiac output and increased ventricular filling pressures compared to control and nitroprusside groups. CONCLUSIONS: Esmolol was associated with greater spinal cord perfusion pressure, but adverse hemodynamic effects, when compared with nitroprusside during thoracic aortic cross-clamping. When only surviving dogs (4 control, 5 esmolol, 6 nitroprusside) are considered, the incidence of neurologic deficit was greater in nitroprusside-treated dogs than in either control or esmolol-treated dogs. No difference in outcome was present when all dogs are considered.

Adrenergic beta-Antagonists↗
PubMed2001

Chemokine antagonist infusion promotes axonal sparing after spinal cord contusion injury in rat.

Spinal cord injury produced by mechanical contusion causes the onset of acute and chronic degradative events. These include blood brain barrier disruption, edema, demyelination, axonal damage and neuronal cell death. Posttraumatic inflammation after spinal cord injury has been implicated in the secondary injury that ultimately leads to neurologic dysfunction. Studies after spinal cord contusion have shown expression of several chemokines early after injury and suggested a role for them in the ordered recruitment of inflammatory cells at the lesion site (McTigue et al. [1998] J. Neurosci. Res. 53:368-376; Lee et al., [2000] Neurochem Int). We have demonstrated previously that infusion of the broad-spectrum chemokine receptor antagonist (vMIPII) in the contused spinal cord initially attenuates leukocyte infiltration, suppresses' gliotic reaction and reduces neuronal damage after injury. These changes are accompanied by increased expression of bcl-2, the endogenous apoptosis inhibitor, and reduced neuronal apoptosis (Ghirnikar et al. [2000] J. Neurosci. Res. 59:63-73). We demonstrate that 2 and 4 weeks of vMIPII infusion in the contusion-injured spinal cord also results in decreased hematogenous infiltration and is accompanied by reduced axonal degeneration in the gray matter. Luxol fast blue and MBP immunoreactivity indicated reduced myelin breakdown in the dorsal and ventral funiculi. Increased neuronal survival in the ventral horns of vMIPII infused cords was seen along with increased bcl-2 staining in them. Immunohistochemical identification of fiber phenotypes showed increased presence of calcitonin gene related peptide, choline acetyl transferase and tyrosine hydroxylase positive fibers as well as increased GAP43 staining in treated cords. These results suggest that sustained reduction in posttraumatic cellular infiltration is beneficial for tissue survival. A preliminary report of this study has been published (Eng et al. [2000] J. Neurochem. 74(Suppl):S67B). In contrast to vMIPII, infusion of MCP-1 (9-76), a N-terminal analog of the MCP-1 chemokine showed only a modest reduction in cellular infiltration at 14 and 21 dpi without significant tissue survival after spinal cord contusion injury. Comparing data on tissue survival obtained with vMIPII and MCP-1 (9-76) further validate the importance of the use of broad-spectrum antagonists in the treatment of spinal cord injury. Controlling the inflammatory reaction and providing a growth permissive environment would enhance regeneration and ultimately lead to neurological recovery after spinal cord injury. J. Neurosci. Res. 64:582-589, 2001. Published 2001 Wiley-Liss, Inc.

Amino Acid Sequence↗
PubMed1998

Adenoviral gene transfer to spinal-cord neurons: intrathecal vs. intraparenchymal administration.

The spinal cord is the site of many chronic, debilitating, neurological disorders that may be amenable to gene therapy. The present study, using quantitative and anatomical methods, examines the ability of replication deficient adenovirus to transfer a transcription cassette composed of the cytomegalovirus promoter driving the expression of the LacZ reporter gene (AdCMVbetagal) to spinal-cord neurons. Rats were microinjected with AdCMVbetagal into the spinal-cord parenchyma or subarachnoid space and sacrificed between 1 and 60 days post-infusion. The spinal cord was assayed for beta-galactosidase (beta-gal) activity fluorometrically (MUG). Intraparenchymal injection resulted in significant beta-gal activity at day 1, which peaked at day 7, and decreased at day 14 (21-, 57- and 9.8-fold of control respectively). The spatial distribution of beta-gal activity on day 7 was confined to the 1-cm section containing the injection site but was detected 2 cm caudal to this section by day 14. Histochemical staining and immunocytochemistry revealed a prominent reaction product in neurons, particularly motor neurons, and glia within the ventral grey matter bilaterally. Intrathecal viral injections showed comparatively modest, yet significant increases in beta-gal activity throughout the spinal cord with the greatest activity (170% control) closest to the catheter tip. This study demonstrates that AdCMVbetagal injected into the ventral spinal cord results in extensive in vivo neuronal gene transfer with beta-gal activity reaching a peak by day 7 and remaining detectable at 60 days. Intrathecal viral injections result in greater spatial distribution but a comparatively lower level of expression.

Adenoviridae↗
PubMed1994

Hyperbaric oxygen therapy: implications for spinal cord injury patients with intrathecal baclofen infusion pumps. Case report.

A patient with a cervical spinal cord injury receiving intrathecal baclofen for spasticity control underwent a 7 week course of hyperbaric oxygen therapy to induce healing of an ischial decubitus ulcer. After completion of this treatment and during a routine baclofen infusion pump refill, the actual pump reservoir volume exceeded computer measurements obtained with telemetry. Examination of the physiology of hyperbaric oxygen therapy in relation to infusion pump function revealed that the intraspinal pressures attained during hyperbaric oxygen therapy produced retrograde leakage of cerebrospinal fluid into the infusion pump reservoir.

Adult↗
PubMed2000

Regeneration of lesioned corticospinal tract fibers in the adult rat induced by a recombinant, humanized IN-1 antibody fragment.

Axons in the CNS of higher vertebrates generally fail to regenerate after injury. This lack of regeneration is crucially influenced by neurite growth inhibitory protein constituents of CNS myelin. We have shown previously that a monoclonal antibody (mAb IN-1) capable of binding and neutralizing Nogo-A, a myelin-associated inhibitor of neurite growth, can induce long-distance axonal regeneration and increased structural plasticity with improved functional recovery in rat models of CNS injury. In this paper we demonstrate that a partially humanized, recombinant Fab fragment (rIN-1 Fab) derived from the original mAb IN-1, was able to promote long-distance regeneration of injured axons in the spinal cord of adult rats. When infused into a spinal cord injury site, regrowth of corticospinal fibers in 11 of 18 animals was observed after a survival time of 2 weeks. Regenerating fibers grew for >9 mm beyond the lesion site and arborized profusely in the distal cord. Regenerated fibers formed terminal arbors with varicosities in the spinal cord gray matter, strongly resembling synaptic points of contact to neurons in the spinal cord distal to the lesion. In animals that had received a bovine serum albumin solution or a recombinant IN-1 fragment that had been mutated in the antigen binding site (mutIN-1 Fab), no significant growth beyond normal lesion-induced sprouting was observed. Neutralization of endogenous nerve growth inhibitors represents a novel use of recombinant antibody technology with potential therapeutic applications after traumatic CNS lesions.

3T3 Cells↗
PubMedDate not supplied

The evolving role of interventional pain management in oncology.

Patients with cancer frequently experience chronic pain, especially in the terminal phases of illness. Fortunately, most patients (90%) can achieve good pain relief using standard and adjuvant analgesics. For those patients who experience severe pain resistant to traditional analgesic therapies, interventional pain management techniques often provide welcome pain relief. The use of neurolytic substances has been used for many decades but has found a niche in the treatment of pain related to abdominal and pelvic cancers. Simple, percutaneous injections of alcohol or phenol can provide much needed pain relief for patients with pancreatic, colon, or gynecologic cancers. The percutaneous placement of catheters for the chronic infusion of spinal analgesics can provide pain relief for virtually any part of the body. Internal or external infusion pumps can be well managed at home, improving quality of life. The physician treating the pain should be aware of these and other interventional pain management techniques to provide alternative therapies to patients with refractory cancer pain.

Analgesics↗
PubMed1992

Haemodynamic changes during spinal anaesthesia with slow continuous infusion or single dose of plain bupivacaine.

Forty elderly patients, scheduled for orthopaedic surgery of the hip or knee were studied. Twenty patients received a single-dose spinal anaesthesia with 3 ml of plain 0.5% bupivacaine (SDSA group). Twenty patients received continuous spinal anaesthesia using a 32- or 22-gauge catheter. A bolus of 1.0 ml of plain 0.5% bupivacaine was given to ten patients and 0.5 ml to another ten, continued by an infusion at a rate of 2 ml/h. The spread of analgesia and haemodynamic changes (central venous pressure, arterial pressures, need for sympathomimetic medication) were registered. The mean dose of bupivacaine was 2.9 ml (range 1.5-5 ml) in the CSA group (3.0 ml in the SDSA group). Eight patients in the CSA group needed medication for pain during surgery compared to five patients in the SDSA group (n.s.). The median level of pinprick analgesia at 60 min was T11 in the CSA and T6.5 in the SDSA group (P less than 0.01). The mean maximum decreases in CVP and MAP were quite similar in the CSA and SDSA group (2.1 vs 2.8 mmHg (0.3 vs 0.4 kPa) and 17 vs 21 mmHg (2.3 vs 2.8 kPa), respectively) (n.s.). Six patients in the SDSA group and four patients in the CSA group needed sympathomimetic medication. It is concluded that titration of bupivacaine for spinal anaesthesia caused only minor haemodynamic changes which were similar to those after single-dose spinal bupivacaine.

Aged↗
PubMedDate not supplied

High-tech pain management utilizing multiple analgesics--a case study.

Intraspinal delivery of opioids is a proven method of pain management therapy for severe cancer pain. Effective analgesia can be achieved with spinal opioid infusions while minimizing central side effects such as sedation, nausea, and severe constipation. Indications for intraspinal opioids include unmanageable side effects with increasing doses of oral or parenteral opioids or little or no pain relief with increasing dosages of strong opioids. The purpose of this case study is to illustrate the multidisciplinary approach required and multiple analgesics needed to effectively assess and manage a challenging pain management situation. This patient required the administration of intraspinal morphine, intravenous hydromorphone, and intravenous midazolam in order to effectively manage his pain. The use of spinal analgesia and multiple analgesics offers challenges to oncology and hospice nurses but is an effective modality for otherwise intractable cancer pain.

Carcinoma, Non-Small-Cell Lung↗
PubMed2002

Effect of epidural infusion of isobaric 2% lidocaine on spinal cord ganglionic neurons.

We analyzed morphological and histoenzymologic changes in spinal cord ganglionic neurons of mongrel dogs caused by epidural infusion of isobaric 2% lidocaine. Lidocaine produced no pathological structural and metabolic alterations in the nervous tissue. Both epidural infusion of 0.9% NaCl and lidocaine produced some morphofunctional rearrangements in spinal ganglionic neurons. These alterations were within the limits of physiological norm and probably attested to functional response of the examined nerve tissue structures to epidural infusion.

Analgesics↗
PubMed2004

Continuous intrathecal infusion of hydromorphone: safety in the sheep model and clinical implications.

OBJECTIVE: To determine the safety of hydromorphone delivered by continuous intrathecal infusion via implanted delivery systems in sheep. DESIGN: Sheep implanted with intrathecal infusion systems were randomly assigned to receive either 1.5, 3, or 6 mg/day hydromorphone HCl or saline control (3 sheep/dose level) at a fixed infusion rate of 1.92 mL/day for 28-31 days. Infusions were initiated approximately 5 days after surgical implantation of the delivery systems (pumps and intrathecal catheters), and investigators were blinded to doses administered. An additional group of sheep (N=3) received hydromorphone (open label) at a dose of 12 mg/day. All animals were examined daily during drug infusion for changes in behavior and neurologic function. Cerebrospinal fluid was analyzed for protein, cytology, and hydromorphone concentration in samples collected prior to and at the end of drug infusion. The spinal cord with the catheter in situ was removed en bloc and fixed in formalin for microscopic analysis. RESULTS: All sheep receiving intrathecal hydromorphone exhibited gaiting deficits and biting behavior over the caudal lumbar area above the infusion site. Animals treated with 12 mg/day were sedate and lethargic, and exhibited repeated biting behavior over the caudal lumbar area during the study. No lesions were noted in any animal upon gross evaluation of the spinal cord. Microscopic changes were comparable between hydromorphone- and saline-treated animals with one exception. Mild inflammation 5 cm cranial to the catheter tip was present in two of three sheep receiving 12 mg/day and in one of three sheep receiving 1.5 mg/day. Mild chronic inflammation hydromorphone in the vicinity of the catheter was also presented in saline-treated animals. CONCLUSIONS: Hydromorphone was not associated with inflammatory mass formation in the sheep model. Further studies are necessary to determine whether hydromorphone is a safer alternative to morphine for continuous intrathecal infusion for the treatment of chronic pain.

Animals↗
PubMed1994

Protection against spinal cord ischaemia: one-shot infusion of hypothermic solution.

The protective effect of a one-short infusion of a range of low-temperature hypothermic solutions against spinal cord ischaemia was investigated. Forty rabbits were allocated into five groups each of eight animals. The abdominal aorta of each rabbit was clamped distal to the left renal artery, and also occluded for 30 min above the iliac bifurcation with an inflated 50-gauge French balloon catheter. Ringer's solution with lactate was infused through the catheter port distal to the balloon, at various temperatures (group I, uninfused control; group II, 33 degrees C; group III, 23 degrees C; group IV, 13 degrees C; and group V, 3 degrees C). The neurological status of the hind limbs was assessed on the second postoperative day using the criteria of Tarlov. A further eight rabbits underwent laminectomy at L2 or L3. Temperature probes were inserted into the spinal cord and the cord temperature monitored continuously during infusion in four rabbits from each of groups I and V. Spastic paraplegia occurred in five rabbits in group I, three in group II, and two in group III. Four rabbits in groups II and III, seven in group IV and all eight in group V showed complete recovery of neurological function. The infusion of 3 degrees C solution achieved significantly lower spinal cord temperatures in group V after aortic clamping, compared with the temperatures in group I (P < 0.001-0.005). It was concluded that protection against spinal cord ischaemia and prevention of postoperative paraplegia are promoted as the temperature of the hypothermic infusion solution is lowered.

Animals↗
PubMed1994

The effect of methylprednisolone, naloxone, and spinal cord trauma on four liver enzymes: observations from NASCIS 2. National Acute Spinal Cord Injury Study.

In order to determine the impact of extremely large doses of methylprednisolone, naloxone, or of spinal cord injury itself, on liver enzymes, we examined the results of SGOT, SGPT, alkaline phosphatase and total bilirubin tests obtained 24 hours, 3 and 10 days after the end of the study drug infusions in spinal cord injured patients entered in the National Acute Spinal Cord Injury Study. The mean values of four liver enzymes, the amount of change between 24 hours and 3 and 10 days post infusion, and the proportion of liver enzyme levels considered to be abnormal did not appear to be affected by either drug protocol. Even when controlling for drug protocol and severity of injury (complete vs incomplete), variation in enzyme levels appeared to be the result of the spinal cord injury, not study drugs. Spinal cord injury is routinely treated with the NASCIS dose of methylprednisolone in many countries. It is reassuring to find no evidence of compromised liver function from this steroid protocol.

Alanine Transaminase↗
PubMed2004

Prevention of postischemic spinal cord injury by means of regional infusion of adenosine and L-carnitine dissolved in normothermic saline.

Spinal cord ischemia still remains an unsolved problem in modern aortic surgery. In this study, we investigated the effectiveness of combined agents such as adenosine and L-carnitine infused to the isolated segment of abdominal aorta in a rabbit model. Twenty-eight rabbits divided into four groups underwent 40 min of isolated infrarenal aortic occlusion. Group I animals received no medication. Group II received an infusion of 100 mg/kg L-carnitine in normothermic saline over the first 10 min of ischemia. Group III received 50 mg adenosine, and group IV received a combination of the two agents in the same fashion. Spinal cord function was evaluated at 24 and 72 hr after operation on the basis of Tarlov scale and similar results were obtained. After a second evaluation, spinal cords were harvested for histological examination. Group I animals were all paraplegics. Spinal cord function was partially intact in two of the group II animals with Tarlov scores of 5 in two and 4 in two whereas one of the rabbits could not hop with a score of 3, and the remaining two could not sit with scores of 1 and 0. The spinal cord function of group III animals was intact with Tarlov scores of 5 in three, 4 in two, and 3 and 1 in remaining ones. In the group IV animals, it was fully intact with Tarlov scores of 5. Histological examination in group I revealed marked enlargement of the vacuoles of glial cells in the white matter of spinal cord. Glial cells were deteriorated in some locations in group II whereas they were mostly protected in the third group. In group IV, histological examination revealed no evidence of spinal cord injury. In conclusion, combined infusion of adenosine and L-carnitine provided better protection against postischemic spinal cord injury than individual infusion of these agents.

Adenosine↗
PubMed1998

Effect of intrathecal nimodipine on spinal cord blood flow and evoked potentials in the normal or injured cord.

A method was developed for administering intrathecal pharmacotherapy in a rat model of spinal cord injury. The effects of intrathecal administration of nimodipine on spinal cord blood flow (SCBF) and evoked potentials (EPs) were measured in the normal and injured spinal cord. It had previously been shown that systemic nimodipine caused severe hypotension after spinal cord injury. After baseline SCBF and EPs, 15 uninjured rats were blindly allocated to one of three groups: one placebo group (n = 5); and two groups with intrathecal nimodipine, 0.05 mg/kg (n = 5), or 0.2 mg/kg (n = 5). Ten other rats received a 35 g acute clip compression injury of the spinal cord for 1 minute and, were allocated to one of two groups: placebo (n = 5); and intrathecal nimodipine 0.05 mg/kg (n = 5) given 60 min after injury. In the uninjured groups, neither 0.05 nor 0.2 mg/kg of nimodipine increased SCBF during, or 30 min after, intrathecal infusion. However, the mean arterial blood pressure (MABP) decreased significantly to 69.73.1% after the infusion of 0.2 mg/kg nimodipine and did not recover by 98 min. In all three groups of uninjured rats, the amplitude of the cerebellar EP was decreased 30 min after infusion. After spinal cord injury, there were significant decreases in MABP, SCBF and EP amplitude in both placebo and treatment groups, but there was no therapeutic benefit from nimodipine. Thus, intrathecal infusion of nimodipine did not prevent the hypotension encountered with systemic administration and exerted no beneficial effect on SCBF or EPs after acute spinal cord injury.

Animals↗
PubMed1993

Joint inflammation and hyperalgesia are reduced by spinal bicuculline.

Knee joint injection of kaolin and carrageenan produces acute inflammation with localized joint swelling and increased temperature. This inflammation results in behavioral changes, including limping and guarding of the limb, and heat hyperalgesia. Prior spinal cord infusion of bicuculline, a gamma amino butyric acidA (GABAA) receptor antagonist, significantly reduces the severity of joint inflammation and prevents the development of heat hyperalgesia. In contrast, infusion of a GABAB receptor antagonist does not alter the arthritis. Therefore, these data support the existence of a central pathway involving GABAA receptors in the spinal cord that influences the development of peripheral inflammation. We suggest that primary afferent depolarization and accompanying dorsal root reflexes play a significant role in the development of peripheral inflammation.

Animals↗