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.

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.

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.

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.

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.

Continuous electroencephalographic monitoring and selective shunting reduces neurologic morbidity rates in carotid endarterectomy.

PURPOSE: The role of continuous electroencephalographic (EEG) monitoring during carotid endarterectomy was evaluated in this retrospective review. METHODS: We analyzed data from 902 consecutive carotid endarterectomy procedures performed with vein patch angioplasty. In 591 operations from 1980 to 1988 we did not use intraoperative EEG monitoring or shunting (non-EEG group). Continuous intraoperative EEG monitoring and selective shunting were used in 311 procedures from 1988 to 1994 (EEG group). The patients' mean age was higher in the EEG group (68.8 years; range, 41 to 87 years) than in the non-EEG group (66.2 years; range, 34 to 90 years; p < 0.001). There was also a significantly higher incidence of hypertension (56.2% vs 41.9%) and redo operations (5.4% vs 2.54%) in the EEG group than in the non-EEG group (p < 0.05). The operative technique was identical in both groups. We defined a significant EEG change as a greater than 50% reduction of the amplitude of the faster frequencies, a persistent increase of delta activity, or both. RESULTS: In the EEG group, acute EEG changes occurred in 40 patients (12.8%); 31 (77.5%) unilateral and ipsilateral to the operated carotid artery, and nine (22.5%) bilateral. In five patients (12.5%) the changes correlated with an intraoperative episode of hypotension, and after normal blood pressure was restored the EEG returned to normal. In 35 procedures (87.5%) a carotid shunt was inserted. In 33 of those patients the EEG returned to baseline, in one patient there was a significant improvement, and in one patient the EEG changes persisted. Postoperative hospital strokes occurred in one patient (0.32%) in the EEG group and in 13 patients (2.19%) in the non-EEG group (p < 0.05). All strokes (n = 14) were ipsilateral to the operated carotid artery. Of the 13 strokes in the non-EEG group nine were major and four were minor. The one stroke in the EEG group was embolic in origin and occurred before carotid cross-clamping; it was associated with profound EEG changes that did not reverse after placement of a shunt. In the total group (n = 902), intraoperative EEG monitoring was inversely associated with postoperative stroke (p < 0.05). CONCLUSION: The overall neurologic morbidity rate was significantly lower in the EEG group than in the non-EEG group, therapy demonstrating the value of intraoperative EEG monitoring in carotid endarterectomy.

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.

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.