Analgesia during labour by continuous infusion epidurals.
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Anesthesia, Obstetrical↗
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Low dose ketamine: an ideal supplementary anaesthesia for spinal block.
In a double blind clinical trial 100 adult patients were randomly divided into 2 groups. In group I after spinal block slow injection of diazepam (0.1 mg/kg) was followed by placebo (0.5 mg/kg as bolus and 0.5 mg/kg/hour in infusion). In group II patients, after spinal block slow injection of diazepam (0.1 mg/kg) was followed by injection of ketamine (0.5 mg/kg as bolus and 0.5 mg/kg/hour as infusion). Low dose of ketamine in combination with diazepam significantly improves quality of anaesthesia, gives better cardiovascular stability without significant increase in complication rate and significantly improves patients' acceptance for the technique.
Anesthesia, Intravenous↗
Low dose epidural bupivacaine/fentanyl infusion does not mask uterine rupture.
A patient is described in whom the symptoms and signs of uterine rupture were not masked by combined spinal epidural analgesia with an epidural infusion of 0.1% bupivacaine and 1.5 microg ml(-l) fentanyl. Early recognition of the dehiscence of a previous caesarean section scar resulted in an excellent neonatal and maternal outcome.
Journal Article↗
Regeneration of adult rat spinal cord is promoted by the soluble KDI domain of gamma1 laminin.
Regeneration in the central nervous system (CNS) of adult mammals is hampered by formation of a glial scar and by proteins released from the myelin sheaths of injured neuronal pathways. Our recent data indicate that the KDI (Lys-Asp-Ile) domain of gamma1 laminin neutralizes both glial- and myelin-derived inhibitory signals and promotes survival and neurite outgrowth of cultured human spinal cord neurons. We show that after complete transection of the adult rat spinal cord, animals receiving onsite infusion of the KDI domain via osmotic mini-pumps recover and are able to sustain their body weights and walk with their hindlimbs. Animals treated with placebo suffer from irreversible hindlimb paralysis. Microscopic and molecular analyses of the spinal cords indicate that the KDI domain reduces tissue damage at the lesion site and enables neurite outgrowth through the injured area to effect functional recovery of the initially paralyzed animals. That the KDI domain enhances regeneration of acute spinal cord injuries in the adult rat suggests that it may be used to promote regeneration of spinal cord injuries in humans.
Animals↗
Cyproheptadine for intrathecal baclofen withdrawal.
OBJECTIVE: To evaluate the efficacy of cyproheptadine in the management of acute intrathecal baclofen (ITB) withdrawal. DESIGN: Descriptive case series. SETTING: University hospital with a comprehensive in- and outpatient rehabilitation center. PARTICIPANTS: Four patients (3 with spinal cord injury, 1 with cerebral palsy) with implanted ITB infusion pumps for treatment of severe spasticity, who had ITB withdrawal syndrome because of interruption of ITB infusion. INTERVENTIONS: Patients were treated with 4 to 8mg of cyproheptadine by mouth every 6 to 8 hours, 5 to 10mg of diazepam by mouth every 6 to 12 hours, 10 to 20mg of baclofen by mouth every 6 hours, and ITB boluses in some cases. MAIN OUTCOME MEASURES: Clinical signs and symptoms of ITB withdrawal of varying severity were assessed by vital signs (temperature, heart rate), physical examination (reflexes, tone, clonus), and patient report of symptoms (itching, nausea, headache, malaise). RESULTS: The patients in our series improved significantly when the serotonin antagonist cyproheptadine was added to their regimens. Fever dropped at least 1.5 degrees C, and heart rate dropped from rates of 120 to 140 to less than 100bpm. Reflexes, tone, and myoclonus also decreased. Patients reported dramatic reduction in itching after cyproheptadine. These changes were associated temporally with cyproheptadine dosing. DISCUSSION: Acute ITB withdrawal syndrome occurs frequently in cases of malfunctioning intrathecal infusion pumps or catheters. The syndrome commonly presents with pruritus and increased muscle tone. It can progress rapidly to high fever, altered mental status, seizures, profound muscle rigidity, rhabdomyolysis, brain injury, and death. Current therapy with oral baclofen and benzodiazepines is useful but has variable success, particularly in severe cases. We note that ITB withdrawal is similar to serotonergic syndromes, such as in overdoses of selective serotonin reuptake inhibitors or the popular drug of abuse 3,4-methylenedioxymethamphetamine (Ecstasy). We postulate that ITB withdrawal may be a form of serotonergic syndrome that occurs from loss of gamma-aminobutyric acid B receptor-mediated presynaptic inhibition of serotonin. CONCLUSION: Cyproheptadine may be a useful adjunct to baclofen and benzodiazepines in the management of acute ITB withdrawal syndrome.
Acute Disease↗
Aprotinin reduces blood loss during spinal surgery in children.
STUDY DESIGN: A prospective blinded, randomized controlled study compared the effect of a perioperative infusion of aprotinin versus placebo during long segment spinal fusions in children. OBJECTIVES: To determine whether aprotinin decreases blood loss and transfusion requirements in pediatric patients with spinal deformities undergoing posterior spinal fusions of seven or greater segments. SUMMARY OF BACKGROUND DATA: Blood loss is a major cause of morbidity during long segment spinal fusion. Several preoperative and intraoperative techniques are currently used to reduce blood loss and transfusion requirements. Aprotinin, an antifibrinolytic and anti-inflammatory agent, has been used to decrease blood loss in cardiac surgical patients. We designed a prospective, randomized, and blinded controlled study to evaluate aprotinin's efficacy in reducing bleeding during pediatric spine surgery. METHODS: After obtaining informed written consent, we studied 44 children and adolescents who were anticipated to be at higher risk for major blood loss during posterior spinal fusion. Children were randomly assigned to receive high dose aprotinin or placebo infusion during the perioperative period. Patients were assessed for blood loss, transfusion requirements, days in the intensive care unit, and days in hospital. RESULTS: Demographics in the two groups of patients were similar. The study demonstrated a significant reduction in estimated blood loss (aprotinin 545 cc, placebo 930 cc) and transfusion requirements (aprotinin 1.1 U, placebo 2.2 U). The duration of intensive care unit admission was similar in the two groups, as was the time until discharge. CONCLUSIONS: This randomized, blinded study suggests that aprotinin significantly decreased blood loss and transfusion requirements in pediatric and adolescent scoliosis surgical patients at increased risk for intraoperative bleeding.
Adolescent↗
Thiopental produces immobility primarily by supraspinal actions in rats.
The spinal cord mediates most of the immobilizing action of inhaled anesthetics. In the present study we investigated whether spinal or supraspinal sites mediate the immobilizing action of thiopental in rats. Thiopental was administered IV, intrathecally (IT), intracerebroventricularly (ICV), or simultaneously IT and ICV. Only the IV infusion produced anesthesia, defined as immobility in response to application of a tail clamp (i.e., the equivalent of minimum alveolar concentration, MAC). Consequently, the MAC-sparing effect (for isoflurane) of thiopental was used to assess the immobilizing contribution of IT and ICV infusions of thiopental. Thiopental concentrations were determined in whole brain, spinal cord, and a slice of cerebral cortex distant from the infusion sites. These concentrations were correlated with the MAC-sparing effect of the thiopental infusions in a multiple regression model. To assess the rate at which thiopental penetrates the cord, rat spinal cords were equilibrated in a bath of thiopental ex vivo and the concentration of thiopental in the cord was measured as a function of equilibration time. This was repeated in vivo with IT infusions of thiopental spanning the time of the behavioral studies. We found that IT or ICV infusion of thiopental 25 microg/min decreased isoflurane MAC <25%. The associated thiopental concentrations in the spinal cord after IT infusion, and in the whole brain after ICV infusion of 25 microg/min thiopental, exceeded by 500% and 680%, respectively, the concentrations found in the spinal cord and in the whole brain after IV infusion of thiopental in a dose that produced anesthesia in the absence of isoflurane. The percentage decrease in the MAC of isoflurane correlated primarily with the concentration of thiopental found in cerebral tissue not in contact with the cerebral ventricles. The spinal cord infusion produced an approximately 20% decrease in MAC. Ex vivo IT thiopental readily diffused into the spinal cord, with a time constant of approximately 1 h. We conclude that, unlike inhaled anesthetics, the immobilizing action of thiopental is largely supraspinal. Centers in the brain other than those near the third and fourth ventricles produce the greatest effect.
Anesthetics, Inhalation↗
Activation of group III metabotropic glutamate receptors inhibits the production of RANTES in glial cell cultures.
The chemokine RANTES is critically involved in neuroinflammation and has been implicated in the pathophysiology of multiple sclerosis. We examined the possibility that activation of G-protein-coupled metabotropic glutamate (mGlu) receptors regulates the formation of RANTES in glial cells. A 15 hr exposure of cultured astrocytes to tumor necrosis factor-alpha and interferon-gamma induced a substantial increase in both RANTES mRNA and extracellular RANTES levels. These increases were markedly reduced when astrocytes were coincubated with l-2-amino-4-phosphonobutanoate (l-AP-4), 4-phosphonophenylglycine, or l-serine-O-phosphate, which selectively activate group III mGlu receptor subtypes (i.e., mGlu4, -6, -7, and -8 receptors). Agonists of mGlu1/5 or mGlu2/3 receptors were virtually inactive. Inhibition of RANTES release produced by l-AP-4 was attenuated by the selective group III mGlu receptor antagonist (R,S)-alpha-methylserine-O-phosphate or by pretreatment of the cultures with pertussis toxin. Cultured astrocytes expressed mGlu4 receptors, and the ability of l-AP-4 to inhibit RANTES release was markedly reduced in cultures prepared from mGlu4 knock-out mice. This suggests that activation of mGlu4 receptors negatively modulates the production of RANTES in glial cells. We also examined the effect of l-AP-4 on the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. l-AP-4 was subcutaneously infused for 28 d by an osmotic minipump that released 250 nl/hr of a solution of 250 mm of the drug. Detectable levels of l-AP-4 ( approximately 100 nm) were found in the brain dialysate of EAE rats. Infusion of l-AP-4 did not affect the time at onset and the severity of neurological symptoms but significantly increased the rate of recovery from EAE. In addition, lower levels of RANTES mRNA were found in the cerebellum and spinal cord of EAE rats infused with l-AP-4. These results suggest that pharmacological activation of group III mGlu receptors may be useful in the experimental treatment of neuroinflammatory CNS disorders.
Aminobutyrates↗
Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation.
Sensory axons in the adult spinal cord do not regenerate after injury. This is essentially because of inhibitory components in the damaged CNS, such as myelin-associated inhibitors and the glial scar. However, if the sciatic nerve is axotomized before injury of the dorsal column, injured axons can regenerate a short distance in the spinal cord. Here, we show that sciatic nerve transection results in time-dependent phosphorylation and activation of the transcription factor, signal transducer and activator of transcription 3 (STAT3), in dorsal root ganglion (DRG) neurons. This effect is specific to peripheral injuries and does not occur when the dorsal column is crushed. Sustained perineural infusion of the Janus kinase 2 (JAK2) inhibitor AG490 to the proximal nerve stump can block STAT3 phosphorylation after sciatic nerve transection and results in reduced growth-associated protein 43 upregulation and compromised neurite outgrowth in vitro. Importantly, in vivo perineural infusion of AG490 also significantly attenuates dorsal column axonal regeneration in the adult spinal cord after a preconditioning sciatic nerve transection. We conclude that STAT3 activation is necessary for increased growth ability of DRG neurons and improved axonal regeneration in the spinal cord after a conditioning injury.
Animals↗
BMP 2--Genetics Institute/ Medtronic-Sofamor Danek/Integra. Bone morphogenetic protein 2--Genetics Institute/ Medtronic-Sofamor Danek/Integra, INFUSE Bone Graft, recombinant human bone morphogenetic protein 2--Genetics Institute/Medtronic-Sofamor Danek/Integra, RhBMP 2--Genetics Institute/Medtronic-Sofamor Danek/Integra.
Genetics Institute (Wyeth) is collaborating with Medtronic-Sofamor Danek (which specialises in spinal reconstruction) and Integra Life Sciences to develop a BMP 2 product [INFUSE Bone Graft] for use in spinal reconstruction in North America. The INFUSE Bone Graft product has been approved for use in lumbar interbody spinal fusion procedures in the USA and is in phase III trials for use in lumbar posterolateral spinal fusion procedures. During the procedure, damaged disc is replaced with a collagen sponge (Integra's Absorbable Collagen Sponge) soaked with BMP 2, which is held in place within an implanted cage device (LT-CAGE Lumbar Tapered Fusion Devise); the fusion process subsequently requires several months to complete. However, the patient is able to leave hospital the day after the operation, whereas in conventional spinal surgery a longer recovery time is required. The procedure supersedes the use of autograft bone as it uses a recombinant human bone morphogenic protein, rhBMP-2, which induces the body to grow its own bone where required. Genetics Institute has cloned and expressed bone morphogenic proteins 1-7 and established manufacturing processes by recombinant DNA technology. Bone morphogenic proteins may be useful in the treatment of osteoporosis and orthopaedic trauma. BMP 2 is also being developed for bone regeneration as an implanted device and as an injectable formulation. Genetics Institute is also collaborating with Integra LifeSciences to develop a formulation of BMP 2 with Integra's absorbable collagen-based structures for fracture treatment, which is awaiting approval in the USA.
Bone Morphogenetic Protein 2↗
Treatment of spasticity in a spinal cord-injured patient with intrathecal morphine due to intrathecal baclofen tolerance--a case report and review of literature.
STUDY DESIGN: Case report. OBJECTIVE: To report treatment of spasticity in a spinal cord-injured person with intrathecal morphine after the person developed tolerance to intrathecal baclofen. METHOD: Spasticity in a 36-year-old man with T6 complete paraplegia was treated with increasing doses of intrathecal baclofen. When he developed tolerance to intrathecal baclofen, he was given continuous infusion of morphine intrathecally. SETTING: Regional Spinal Injuries Centre, UK. RESULTS: Spasticity was adequately controlled by intrathecal morphine. CONCLUSION: In spinal cord-injured patients with severe spasticity, who become tolerant to intrathecal baclofen, treatment with intrathecal morphine may be useful.
Adult↗
Methylprednisolone and spinal cord injury.
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Acute Disease↗
Chronic pain after spinal cord injury: clinical characteristics.
The clinical characteristics of chronic pain in spinal cord injury patients are controversial. The authors prospectively evaluated 81 patients with chronic pain due to spinal cord lesions. The mean pain intensity according to the visual analogue scale was 9.4. The most common description of pain was a sensation of burning. The initial pain was more severe in patients presenting with myelopathy due to gunshot injuries (p < 0.001). The pain intensity was not associated with the magnitude of the spinal lesion, location of the lesion, occurrence of myofascial pain syndrome or onset of pain. Pain after spinal cord injury was severe, males were more frequently affected and it was more intense when it was the result of gunshot injury. In about 38% of the patients, pharmacological and rehabilitative procedures were effective. Dorsal root entry zone lesion was effective for the treatment of transitional pain in patients with complete section of the spinal cord, spinal cord stimulation was effective for patients with partial lesions of the spinal cord and intrathecal opioid infusion was effective for both conditions.
Adult↗
Intrinsic spinal cord catheter placement: implications of new intractable pain in a patient with a spinal cord injury.
We present a case of new intractable flank pain after intrathecal infusion system placement in a 45-yr-old man with a history of a T12 spinal cord injury with dysesthetic leg pain. Pain after intrathecal infusion system placement was evaluated by magnetic resonance imaging and the catheter was found to be intraparenchymal. The patient was treated by cessation of infusion and surgical removal of the system. Before surgical removal, the pump was turned off and the patient's flank pain resolved. Increased vigilance is warranted when caring for paraplegic patients. When new pain persists, intrathecal medication tapering should be considered.
Analgesics, Opioid↗
Studies of morphine and D-ala2-D-leu5-enkephalin (DADLE) cross-tolerance after continuous intrathecal infusion in the rat.
To determine the cross tolerance to the antinociceptive effects of mu and delta opioids in the spinal cord, rats received a 7-day infusion of one of three concentrations each of morphine (2, 6, or 20 nmol/h) or D-ala2-D-leu5-enkephalin (DADLE) (2, 6, or 20 nmol/h). A constant-rate (1 microliter/h), constant-dose intrathecal infusion pump was used. On day 7, the magnitude of tolerance was assessed by establishing dose-response curves for the effect of the chronic drug given as an intrathecal bolus. Cross-tolerance was assessed in separate groups of animals with identical infusions by establishing morphine dose-response curves in DADLE-tolerant animals and DADLE dose-response curves in morphine-tolerant animals. Each infused animal was used for a single bolus injection. For morphine and DADLE tolerance, a parallel rightward shift in the dose-response curve was produced with the degree of shift proportional to the log of the infusion dose. Thus, at the infusion rate of 6 nmol/h for either morphine or DADLE, the shift of the tolerance dose-response curves was 55- and 33-fold, respectively. Morphine and DADLE cross-tolerance was also detected as shown by rightward shifts of the cross-tolerance dose-response curves; however, these shifts were relatively minor compared to the shifts seen in the tolerance dose-response curves of animals tested with the same agent as infused.(ABSTRACT TRUNCATED AT 250 WORDS)
Analgesia↗
Volume kinetics of Ringer's solution during induction of spinal and general anaesthesia.
The kinetics of an i.v. infusion of 20 ml x kg(-1) of Ringer's solution over 60 min was studied in patients undergoing spinal (n=10) and general (n=10) anaesthesia. The induction resulted in similar changes in volume kinetic parameters in both groups. When a one-volume model was employed (n=8), however, the infusion expanded a smaller body fluid space in the four patients who had received preoperative enteric lavage (3.3 vs 8.3 litres), which is consistent with hypovolaemia. When a two-volume model was statistically justified (n=12), the induction reduced the rate of fluid equilibration between a fairly small central (V1, mean 1.4 litres) and a peripheral body fluid space by about 50% (P<0.01). The kinetic analysis suggested that a rapid fluid load of 350 ml given over 2 min just after the induction could possibly prevent arterial hypotension because of central hypovolaemia. This was confirmed in five additional patients.
Adult↗
Afferent renal nerves and hypertension.
Adenosine-sensitive nerve endings have been found in the renal pelvis which when stimulated increase sympathetic activity producing hypertension. When urinary adenosine concentration is lowered by intrarenal infusion of adenosine deaminase in one-kidney one-clip rats, peripheral sympathetic nervous system activity and arterial pressure decrease if the renal nerves are intact. These data suggest that a stimulus for afferent renal nerve activity in one-kidney, one-clip hypertension is intrarenal adenosine. This intrarenal adenosine hypertensive reflex was examined further observing the responses to renal pelvic xylocaine infusion, selective renal deafferentation, adrenal demedullation and spinal cord transection (T6). The intrarenal adenosine hypertensive reflex was interrupted by renal pelvic xylocaine infusion, renal deafferentation and adrenal demedullation in normotensive and one-kidney, one-clip hypertensive animals. The intrarenal adenosine hypertensive reflex persisted after spinal cord transection (T6). These data support the concept that adenosine-sensitive intact afferent renal nerves located in the renal pelvis enhance sympathoadrenal activity resulting in the maintenance of one-kidney, one-clip hypertension and that this intrarenal adenosine-hypertensive response may occur as a spinal-level reflex in the rat.
Adenosine↗
Cold spinoplegia and transvertebral cooling pad reduce spinal cord injury during thoracoabdominal aortic surgery.
OBJECTIVE: We examined the protective effects of the new selective spinal cord cooling by using cold saline infusion into the cross-clamped aorta and a transvertebral cooling pad placed over the lumbar vertebral column from paraplegia caused by ischemic spinal cord injury on thoracoabdominal aortic surgery. METHODS: Eighteen rabbits were divided into three groups: groups I, II, and III (n = 6 for each group). In group I (37 degrees C; 5 mL) and group II (3 degrees C; 5 mL), saline was infused into the isolated aortic segment twice, at 0 and 5 minutes after aortic cross clamping. In group III, a 3 degrees C saline solution plus cooling pads placed just after cross clamping were combined. The infrarenal aorta was then isolated proximally and distally by vascular clamps for 12 minutes. In our preliminary study, only the abdominal aorta just distal to the left renal artery was clamped. At 48 hours after reperfusion, the groups clamped for 12 and 15 minutes were all paraplegic. The time of clamping the aorta was set at 12 minutes as the critical point when paraplegia occurred upon simple clamping of the infrarenal aorta only. The spinal cord temperature was monitored at the L4 level continuously during the procedures in all three groups. At 8, 24, and 48 hours after the operation, hind limb function was estimated by using the Tarlov score, which is often used for evaluating motor function in animals. A histopathologic study using hematoxylin and eosin stains was also performed. RESULTS: At 48 hours after the operation, the Tarlov scores in groups I, II, and III were 0 +/- 0, 2.0 +/- 1.9, and 4.0 +/- 0 (mean +/- SD), respectively. The Tarlov score and histopathologic analysis in group III were significantly superior to those of groups I (P < .01) and II (P < .05). The spinal cord temperature in groups II and III decreased by -1.8 degrees C and -4.3 degrees C at its minimum. The rabbits in group III were also protected from paraplegia. CONCLUSIONS: Selective spinal cord cooling with cold saline infusion into the isolated aortic segment and transvertebral regional cooling can reduce the neurologic damage of spinal cord ischemia.
Animals↗