Effects of intrathecal baclofen on lumbosacral and cortical somatosensory evoked potentials.

We analyzed lumbosacral and cortical somatosensory evoked potentials in three spinal cord injury patients undergoing evaluation of intrathecal baclofen infusion for management of spasticity. The cauda equina propagating root wave (R wave) and conus medullaris postsynaptic responses (S and P waves) were analyzed before and during baclofen infusion. Baclofen abolished the concomitantly recorded H-reflex and markedly suppressed the P wave amplitude and area. The S wave amplitude and area were suppressed to a lesser degree. In contrast, there were no significant changes in cortical somatosensory evoked potentials.

Intrathecal baclofen for intractable axial dystonia.

Following spinal instrumentation for scoliosis, a patient developed intractable axial dystonia refractory to conservative medical management. We describe the successful treatment of this dystonia with a continuous infusion of intrathecal baclofen and the subsequent long-term management.

Protamine-induced circulatory changes.

The effects of rapid protamine administration via the left and right atria were compared. Preliminary studies first confirmed the safety of protamine administration via these routes, although decreases of up to 20 mm Hg were seen in the systolic blood pressure following protamine injection via the right atrium. Seventeen patients undergoing coronary artery bypass graft were studied, of whom nine received protamine via the right atrium and eight via the left atrium. Measurements of arterial pressure, left and right atrial pressure, cardiac output, and calculation of systemic vascular resistance and left ventricular stroke work index were made before and after protamine administration. Plasma histamine levels were measured in left atrial blood samples in 10 patients, before and after protamine injection. No significant change occurred after injection via the left atrial route, whereas a significant decrease in the systolic blood pressure and systemic vascular resistance with a transient increase in the cardiac index occurred after protamine administration via the right atrium. Plasma histamine levels were significantly higher after right atrial injection. It is concluded that histamine is released as protamine traverses the lungs following right atrial injection and produces peripheral vasodilation. Possible mechanisms for histamine release are discussed.

Inhibition of complement, neutrophil, and platelet activation by an anti-factor D monoclonal antibody in simulated cardiopulmonary bypass circuits.

OBJECTIVES: Patients undergoing cardiopulmonary bypass frequently manifest generalized systemic inflammation and occasionally manifest serious multiorgan failure. Inflammatory responses of bypass are triggered by contact of blood with artificial surfaces of the bypass circuits, surgical trauma, and ischemia-reperfusion injury. We studied the effects of specific inhibition of the alternative complement cascade by using an anti-factor D monoclonal antibody (166-32) in extracorporeal circulation of human whole blood used as a simulated model of cardiopulmonary bypass. METHODS: Five healthy blood donors were used in the study. Monoclonal antibody 166-32 was added to freshly collected, heparinized human blood recirculated in a pediatric cardiopulmonary bypass circuit at a final concentration of 18 microg/mL. An irrelevant monoclonal antibody was used as a negative control with the same donor blood in a parallel bypass circuit on the same day. Blood samples were collected at different time points during recirculation for measurement of activation of complement, neutrophils, and platelets by immunofluorocytometric methods and enzyme-linked immunosorbent assays. RESULTS: Monoclonal antibody 166-32 inhibited the alternative complement activation and the production of Bb, C3a, sC5b-9, and C5a. Upregulation of CD11b on neutrophils and CD62P on platelets was also significantly inhibited by monoclonal antibody 166-32. This is consistent with the inhibition of the release of neutrophil-specific myeloperoxidase and elastase and platelet thrombospondin. The production of proinflammatory cytokine interleukin 8 was also suppressed by the antibody. CONCLUSIONS: The alternative complement cascade is predominantly activated during extracorporeal circulation. Anti-factor D monoclonal antibody 166-32 is effective in inhibiting the activation of complement, neutrophils, and platelets. Inhibition of the alternative complement pathway by targeting factor D could be useful in reducing systemic inflammation in patients undergoing cardiopulmonary bypass.

Effects of intrathecal baclofen on chronic spinal cord injury pain.

The pain of 16 patients with spasticity secondary to spinal cord injury was assessed prior to intrathecal baclofen pump implantation and again 6 and 12 months postoperatively. Chronic pain was delineated into neurogenic and musculoskeletal components, noting changes in nature, quality, and severity of pain (visual analogue scale) and use of analgesic medications. Twelve of 16 patients had chronic pain preoperatively and were included in the study. Six patients had neurogenic pain, three had musculoskeletal pain, and three had both pain components. Postoperatively, at both 6- and 12-month intervals, seven patients with neurogenic pain (78%) demonstrated no significant change in pain severity, while in five patients (83%) musculoskeletal pain decreased significantly. Two patients with neurogenic pain (22%) demonstrated an increase in pain severity at both 6- and 12-month intervals. This study suggests that intrathecal baclofen reduces chronic musculoskeletal pain associated with spasticity but does not decrease chronic neurogenic spinal cord injury pain.

Complement activation during cardiac and thoracic vascular operations.

To study complement activation, we evaluated nine patients who underwent cardiac operations requiring cardiopulmonary bypass (CPB) and nine other patients who underwent thoracic vascular operations without CPB. Concentration of C3, as measured by radioimmunoassay, was used as an indicator of complement activation (C3a is a complement-degradation product). In the CPB patients, the C3a level increased tenfold (from baseline value) after the onset of bypass, and continued to increase during bypass. Protamine produced an additional twofold increase in the C3a value, to a peak of 5461 +/- 1360 ng/ml. By 12 hours after surgery, the C3a level had decreased to normal (400 ng/ml). In the non-CPB patients, C3a remained at baseline levels until the administration of protamine, which caused a tenfold increase to a peak of 2281 +/- 293 ng/ml; C3a levels returned to normal 6 hours after operation. The peak postprotamine C3a levels were significantly higher (p < 0.01) in the CPB group than in the non-CPB group. This finding was due to the fact that, during CPB, complement activation occurs via the alternative pathway; the administration of protamine then causes additional activation via the classical pathway. During thoracic vascular operations, however, complement activation occurs only in response to protamine, via the classical pathway.

Assessment of arteriovenous blood flow during retrograde cerebral perfusion.

OBJECTIVE: This study examined arterial and venous blood flow during retrograde cerebral perfusion (RCP) to quantify what proportion of arterial inflow is not recovered as venous outflow. DESIGN: Prospective. SETTING: Community hospital, university setting, single institution. PARTICIPANTS: Twelve patients undergoing reconstructive aortic arch surgery with profound hypothermic circulatory arrest and RCP. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: RCP arterial inflow and venous outflow measurements were recorded at 2-minute intervals for 10 minutes, averaged, and then compared. Only 44.9%+/-16.3% of RCP inflow returned through the aortic arch. The remainder was not recovered. CONCLUSION: Internal jugular venous valves, sequestration, and shunting may contribute to arterial inflow diversion during RCP.

Comparison of two sites of inflow pressure measurement during retrograde cerebral perfusion.

OBJECTIVE: To determine whether internal jugular venous valves influence inflow pressure during retrograde cerebral perfusion. DESIGN: Prospective study. SETTING: Community hospital, university setting, single institution. PARTICIPANTS: Ten patients undergoing reconstructive aortic arch surgery with profound hypothermic circulatory arrest. INTERVENTIONS: During retrograde cerebral perfusion, inflow pressure was continuously measured at 2 separate sites relative to the left internal jugular venous valve (ie, superior vena cava inflow catheter [infravalvular pressure] and rostral left internal jugular vein [supravalvular pressure]). MEASUREMENTS AND MAIN RESULTS: Infravalvular pressure of 29.8 +/- 3.5 mmHg and supravalvular pressure of 22.7 +/- 0.8 mmHg were significantly different (mean difference, 7.1 +/- 3.6 mmHg; p = 0.041). In 8 patients, the pressure difference was <6 mmHg; whereas in 2 patients, the pressure difference was >20 mmHg. Bland and Altman analysis revealed 95% limits of agreement on mean bias of -12.9 to 27.8 mmHg. CONCLUSION: Internal jugular venous valves can obstruct retrograde cerebral perfusion inflow, manifest by an inflow pressure difference between the superior vena cava and internal jugular vein. In the presence of competent internal jugular venous valves, measurement of inflow pressure in the superior vena cava may be an inaccurate estimate of actual cerebral perfusion pressure. Internal jugular vein pressure should be monitored to avoid inadvertent cerebral hypoperfusion.

Effect of methylprednisolone on complement activation during heparin neutralization.

During cardiac surgery, steroids are frequently administered before the initiation of cardiopulmonary bypass (CPB), termed "pre-treatment," to reduce "first phase" complement activation during cardiopulmonary bypass (CPB). "Second phase" complement activation also occurs during heparin neutralization with protamine, although the effects of steroid pretreatment on such activation are unknown. This study was performed in patients undergoing coronary artery bypass graft surgery to determine whether high-dose methylprednisolone pretreatment affected complement activation during heparin-protamine interaction after termination of CPB. In eight patients (group MP), methylprednisolone, 30 mg/kg, was administered before CPB commencement, whereas another eight patients received placebo (group C). By using 125I des Arg radioimmunoassay, C3a, C4a, and C5a were measured in the arterial blood samples drawn before and 10 min after administration of protamine. An increase in C3a and C4a was observed in both groups after protamine, suggesting classic pathway activation (delta C3a: group C, 4,484 +/- 3,320; group MP, 1,394 +/- 1,653; delta C4a: group C, 1,810 +/- 731; group MP, 717 +/- 580). C3a and C4a levels were significantly lower in group MP patients after protamine compared with controls [delta C3a, 3,499 +/- 1,826 (p < 0.05); delta C4a, 1,241 +/- 232 (p < 0.05)]. C5a was not detected in any samples. These results demonstrate that the effect of pretreatment persists beyond the period of CPB and that methylprednisolone inhibits second-phase complement activation during heparin-protamine interaction. These findings have implication for patients with severe anaphylactoid reactions to protamine.

Comparison of intra-arterial and automated oscillometric blood pressure measurement methods in postoperative hypertensive patients.

A comparison of blood pressures measured by direct radial intra-arterial and indirect brachial automated oscillometric methods (Dinamap 1845), was performed in thirty hypertensive post-carotid endarterectomy patients. Five hundred fifty-eight "triplet" readings of systolic, diastolic, and mean blood pressure were compared. Mean differences of 18.92, -6.32, and -0.26 mm Hg, and correlation coefficients of 0.831, 0.724, and 0.776 were calculated for systolic, diastolic, and mean blood pressures, respectively. Mean differences were then calculated within incremental direct systolic pressure ranges of 20 mm Hg and found to become significantly larger with each increasing increment of pressure. These differences ranged from -0.8 to 12.6 and 20.0 to 53.3 mm Hg in the less than 160 and greater than 160 mm Hg groups, respectively, with direct intra-arterial systolic pressures significantly greater than indirect oscillometric systolic pressures in the latter group. The results demonstrate that in the hypertensive pressure range, a significant difference exists in systolic pressure measured by intra-arterial and automated oscillometric methods.

Arterial and venous blood gas analyses during retrograde cerebral perfusion.

OBJECTIVE: To examine arterial and venous blood gas analyses during retrograde cerebral perfusion to quantify oxygen uptake and carbon dioxide production. DESIGN: Prospective. SETTING: Community hospital, university setting, single institution. PARTICIPANTS: Twelve patients undergoing reconstructive aortic surgery with profound hypothermic circulatory arrest and retrograde cerebral perfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 10 minutes of retrograde cerebral perfusion, blood gas analysis (measured at 37 degrees C, without temperature correction) was performed on blood samples drawn simultaneously from the arterial inflow and venous return (collected via aortic arch vessels) sites. Compared with arterial blood samples, PO2 (deltaPO2: 431.2+/-154.9 mm Hg; p<0.05), pH (deltapH: 0.16+/-0.09, p<0.05) and base excess (deltaBE: 1.0+/-0.85; p<0.05) decreased in venous blood samples, whereas PCO2 increased (deltaPCO2: 18.2+/-8.8 mm Hg; p<0.05). An arteriovenous content difference of 2.5+/-1.9 mL/dL reflected a total oxygen extraction of 20.5%+/-15.7%, although most extraction occurred from oxygen in solution. CONCLUSION: These findings suggest that retrograde cerebral perfusion produces cerebral aerobic metabolism.

Diagnostic spinal anaesthesia in chronic spinal cord injury pain.

In a double blind study, 21 patients with chronic spinal cord injury (SCI) pain underwent placement of a lumbar subarachnoid catheter and injection of placebo and lidocaine. The effects on pain intensity, distribution, altered sensations and sensory level of anaesthesia were monitored. Four patients responded briefly to placebo, while 13 demonstrated a mean reduction of pain intensity of 37.8 +/- 37% for a mean duration of 123.1 +/- 95.3 minutes in response to lidocaine. The pain response to subarachnoid lidocaine differed significantly (p less than 0.01) from placebo. Spinal anaesthesia was also associated with changes in pain distribution and altered sensation. A spinal anaesthetic-induced sensory level could not be achieved cephalad to the sensory level of neurological injury in 5 patients who presented with spinal canal obstruction. This study has demonstrated that response to diagnostic spinal anaesthesia in chronic SCI pain is complex, requiring individual interpretation in each patient and consideration of the following factors; symptomatology, etiology, pain perception, spinal canal anatomy, CSF chemistry and local anaesthetic pharmacology.

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.

Chronic pain in a community-based sample of men with spinal cord injury: prevalence, severity, and relationship with impairment, disability, handicap, and subjective well-being.

OBJECTIVE: To assess the prevalence, severity, and correlates of chronic pain in a community-based sample of men with spinal cord injury (SCI). DESIGN: Survey. SETTING: Community. PARTICIPANTS: Seventy-seven men with SCI randomly selected from a sampling frame solicited from the community. METHOD: Participants completed standardized questionnaires assessing many areas of life, were interviewed in their homes, and underwent a physical examination at a hospital. There they were interviewed by an anesthesiologist regarding chronic pain, and a nurse administered objective pain measures. RESULTS: Seventy-five percent of the men reported chronic pain. Chronic pain was associated with more depressive symptoms, more perceived stress, and poorer self-assessed health. Greater intensity of pain was related to less paralytic impairment, violent etiology, and more perceived stress. Area of the body affected by pain was related to independence and mobility. CONCLUSIONS: Because of the high prevalence of chronic pain in the population with SCI and its relation to disability, handicap, and quality of life, health care providers need to give this issue the same priority given to other SCI health issues. Analysis of individual pain components provides better information than assessing overall pain. It is futile to treat SCI pain without giving full attention to subjective factors.

Effects of unilateral, low-frequency, neuromuscular stimulation on superficial circulation in lower extremities of patients with peripheral vascular disease.

The effects of unilateral, low-frequency, neuromuscular stimulation on the circulation in skin of the lower extremities were studied in eight subjects with peripheral vascular disease and eight control subjects with normal peripheral vasculature. Sixty minutes of stimulation (at 2 Hz), of sufficient intensity to produce visible contraction of musculature, was applied through cutaneous electrodes placed over the common peroneal nerve and dorsum of the foot. Systolic and diastolic blood pressure, heart rate, bilateral great-toe photoplethysmographic waveform, and bilateral pedal skin temperature were recorded at 30-min intervals during stimulation and 30 min after stimulation. Mean differences in recordings before and after stimulation were then calculated for each parameter, showing in subjects with peripheral vascular disease significant increases of 5.3 +/- 2.1 mm and 0.5 +/- 0.1 degree C for ipsilateral photoplethysmographic waveform amplitude and pedal skin temperature, respectively. Mean differences for the remaining parameters were not significant. Recorded parameters in the control group did not change after stimulation. These results demonstrate that low-frequency, neuromuscular stimulation produces regional cutaneous vasodilation in subjects with peripheral vascular disease. No evidence of generalized vasodilation after neuromuscular stimulation was found.

Continuous infusion of intrathecal baclofen: long-term effects on spasticity in spinal cord injury.

The effects of intrathecal baclofen infusion were studied in 9 spinal cord injury patients whose spasticity had been refractory to oral medications. In a two stage, placebo controlled trial, baclofen was administered into the lumbar intrathecal space and subsequent clinical and neurophysiologic changes were assessed. In stage 1, 9 patients underwent a 5 day percutaneous infusion of baclofen and placebo via an external pump. Ashworth and reflex scores were assessed at time of enrollment, after infusion of that amount of baclofen which provided optimal spasticity control and after intrathecal infusion of placebo. The mean Ashworth grade decreased from 3.78 +/- 1.34 to 1.16 +/- 0.48 (p less than 0.001) while mean reflex score decreased from 3.57 +/- 1.05 to 0.64 +/- 0.87 (p less than 0.001). These values differed significantly from those associated with placebo therapy (Ashworth grade--2.54 +/- 1.04, p less than 0.001; reflex score--2.56 +/- 1.04, p less than 0.01). Objective improvements in functional abilities and independence were noted in 8 patients, while somatosensory and brainstem auditory evoked potentials were unchanged in all patients. Urodynamic evaluation revealed increased bladder capacity in 3 patients, while in 4 no change was observed. In Stage 2, permanent programmable infusion pumps were implanted in 7 patients who demonstrated a good response during Stage 1. In this group, mean Ashworth score decreased from 3.79 +/- 0.69 to 2 +/- 0.96 (p less than 0.001) and mean reflex score decreased from 3.85 +/- 0.62 to 2.18 +/- 0.43 (p less than 0.001). Baclofen dosage increased from 182 +/- 135 to 528 +/- 266 mcg/day over the 3-22 month follow-up period. Most of the dosage increase occurred within the initial 12 months following infusion pump implantation and tended to plateau thereafter. Minor complications such as catheter dislodgement/kinking and nausea occurred infrequently while no device related infections were observed. There was no clinical evidence of any significant baclofen neurotoxicity either in Stage 1 or 2. The only ambulatory patient developed marked lower extremity weakness during Stage 1 intrathecal baclofen infusion and was temporarily unable to walk. We conclude that continuous administration of intrathecal baclofen is an effective and safe modality for spasticity control in patients who are refractory to oral medications.

Intrathecal baclofen: does tolerance occur?

Concern over the development of tolerance in patients on continuous intrathecal baclofen therapy has arisen as this new form of treatment for spasticity has gained wider use. We have studied time-dose relationships in 18 spinal cord injured patients who have undergone intrathecal baclofen infusion pump implantation since February 1988 in our facility. Our data show that there was a significant increase in baclofen dosage needed to control spasticity during the first 12 months post implantation. After 12 months, however, no significant changes in dosage requirement was detected. In addition, there was no significant difference between completely and incompletely spinal cord injured patients with regard to both the initial dose and the tolerance trend.