Christophe Baufreton

Psychosocial risk factors for chronic low back pain in primary care—a systematic review

BACKGROUND Low back pain (LBP) is a major public health problem, often encountered in primary care. Guidelines recommend early identification of psychosocial factors that could prevent recovery from acute LBP. METHODS To review the evidence on the prognostic value of psychosocial factors on transition from acute to chronic non-specific LBP in the adult general population. Systematic review is the design of the study. A systematic search was undertaken for prospective studies dealing with psychosocial risk factors for poor outcome of LBP in primary care, screening PubMed, PsychInfo and Cochrane Library databases. The methodological quality of studies was assessed independently by two reviewers using standardized criteria before analysing their main results. RESULTS Twenty-three papers fulfilled the inclusion criteria, covering 18 different cohorts. Sixteen psychosocial factors were analysed in three domains: social and socio-occupational, psychological and cognitive and behavioural. Depression, psychological distress, passive coping strategies and fear-avoidance beliefs were sometimes found to be independently linked with poor outcome, whereas most social and socio-occupational factors were not. The predictive ability of a patients self-perceived general health at baseline was difficult to interpret because of biomedical confounding factors. The initial patients or care providers perceived risk of persistence of LBP was the factor that was most consistently linked with actual outcome. CONCLUSION Few independent psychosocial risk factors have been demonstrated to exist. Randomized clinical trials aimed at modifying these factors have shown little impact on patient prognosis. Qualitative research might be valuable to explore further the field of LBP and to define new management strategies.

Heparin coating of extracorporeal circuits inhibits contact activation during cardiac operations

OBJECTIVE Heparin coating reduces complement activation on the surface of extracorporeal circuits. In this study we investigated its effect on activation of the contact system in 30 patients undergoing coronary artery bypass grafting with the use of a heparin-coated (Duraflo II, Baxter Healthcare Corp., Edwards Division, Santa Ana, Calif.; n = 15) or an uncoated extracorporeal circuit (n = 15). METHODS Plasma markers that reflect activation of contact (kallikrein-C1-inhibitor complexes), coagulation (prothrombin fragments F1 + 2), or fibrinolytic (plasmin-alpha 2-antiplasmin complexes) systems were determined before and during the operation. The generation of kallikrein-C1-inhibitor complexes was reduced by 62% (p = 0.06) after the onset of cardiopulmonary bypass and by 43% (p = 0.026) after the cessation of bypass in the group in which a heparin-coated circuit was used compared with the group in which the circuit was uncoated. Generation was reduced by 58% (p = 0.06) when the ratio of kallikrein-C1-inhibitor to prekallikrein after onset of bypass was considered. We detected significant increases in F1 + 2 levels in both groups and increases in plasmin-alpha 2-antiplasmin complexes in the heparin-coated group at cessation of bypass, but no intergroup differences were observed. Thus use of heparin-coated extracorporeal circuits during cardiac operations reduces formation of kallikrein-C1-inhibitor complexes when compared with use of uncoated circuits. The heparin coating is not accompanied by similar reductions in coagulation or fibrinolysis, suggesting that thrombin and plasmin formation during cardiopulmonary bypass occurs mainly independently of the contact system activation.

Inflammatory response to cardiopulmonary bypass using roller or centrifugal pumps

BACKGROUND The inflammatory response in 29 patients undergoing coronary artery bypass grafting using either roller or centrifugal (CFP) pumps was evaluated in a prospective study. METHODS Patients were randomized in roller pump (n = 15) and CFP (n = 14) groups. Terminal complement complex activation (SC5b-9) and neutrophil activation (elastase) were assessed during the operation. Cytokine production (tumor necrosis factor-alpha, interleukin-6, interleukin-8) and circulating adhesion molecules (soluble endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1) were assessed after the operation. RESULTS Release of SC5b-9 after stopping cardiopulmonary bypass and after protamine administration was higher in the CFP group (p = 0.01 and p = 0.004). Elastase level was higher after stopping cardiopulmonary bypass using CFP (p = 0.006). Multivariate analysis confirmed differences between roller pump and CFP groups in complement and neutrophil activation. After the operation, a significant production of cytokines was detected similarly in both groups, with peak values observed within the range of 4 to 6 hours after starting cardiopulmonary bypass. However, interleukin-8 levels were higher using CFP 2 hours after starting cardiopulmonary bypass (p = 0.02). Plasma levels of adhesion molecules were similar in both groups within the investigation period. CONCLUSIONS During the operation, CFP caused greater complement and neutrophil activation. After the operation, the inflammatory response was similar using either roller pump or CFP.

Paradoxical Role of Angiotensin II Type 2 Receptors in Resistance Arteries of Old Rats

The role of angiotensin II type 2 receptors (AT2Rs) remains a matter of controversy. Its vasodilatory and antitrophic properties are well accepted. Nevertheless, in hypertensive rats, AT2R stimulation induces a vasoconstriction counteracting flow-mediated dilation (FMD). This contraction is reversed by hydralazine. Because FMD is also decreased in aging, another risk factor for cardiovascular diseases, we hypothesized that AT2R function might be altered in old-rat resistance arteries. Mesenteric resistance arteries (250 &mgr;m in diameter) were isolated from old (24 months) and control (4 months) rats receiving hydralazine (16 mg/kg per day; 2 weeks) or water. FMD, NO-mediated dilation, and endothelial NO synthase expression were lower in old versus control rats. AT2R blockade improved FMD in old rats, suggesting that AT2R stimulation produced vasoconstriction. AT2R expression was higher in old rats and mainly located in the smooth muscle layer. In old rats, AT2R stimulation induced endothelium-independent contraction, which was suppressed by the antioxidant Tempol. Reactive oxygen species level was higher in old-rat arteries than in controls. Hydralazine improved FMD and NO-dependent dilation in old rats without change in AT2R expression and location. In old rats treated with hydralazine, reactive oxygen species level was reduced in endothelial and smooth muscle cells, and AT2R-dependent contraction was abolished. Thus, AT2R stimulation induced vasoconstriction through activation of reactive oxygen species production, contributing to decrease FMD in old-rat resistance arteries. Hydralazine suppressed AT2R-dependent reactive oxygen species production and AT2R-dependent contraction, improving FMD. Importantly, endothelial alterations in aging were reversible. These findings are important to consider in the choice of vasoactive drugs in aging.

Heparin coating with aprotinin reduces blood activation during coronary artery operations.

BACKGROUND This study was performed to evaluate whether the combination of heparin-coated extracorporeal circuits (ECC) and aprotinin treatment reduce blood activation during coronary artery operations. METHODS Sixty patients were prospectively divided into two groups (heparin-coated ECC and uncoated ECC groups), which were comparable in terms of age, sex, left ventricular function, preoperative aspirin use and consequent intraoperative aprotinin use, number of grafts, duration of aortic cross-clamping, and duration of cardiopulmonary bypass. Blood activation was assessed at different times during cardiopulmonary bypass by determination of complement activation (C3 and C4 activation products C3b/c and C4b/c and terminal complement complex), leukocyte activation (elastase), coagulation (scission peptide fibrinopeptide 1 + 2), and fibrinolysis (D-dimers). RESULTS Univariate analysis showed that heparin-coated ECC, under conditions of standard heparinization, did not reduce perioperative blood loss and need for transfusion. Heparin coating, however, reduced maximum values of C3b/c (446 +/- 212 nmol/L versus 632 +/- 264 nmol/L with uncoated ECC; p = 0.0037) and maximum C4b/c values (92 +/- 48 nmol/L versus 172 +/- 148 nmol/L with uncoated ECC; p = 0.0069). Levels of terminal complement complex, elastase, fibrinopeptide 1 + 2, and D-dimers were not significantly modified by the use of heparin-coated ECC. Multivariate analysis showed that the intergroup differences in maximum C3b/c and C4b/c values were more pronounced in women in part with high baseline values of C3b/c. We also found that aprotinin contributed to the reduction of maximum values of fibrinopeptide 1 + 2 and D-dimers, whereas heparin coating had no significant influence on these parameters. CONCLUSIONS We found no evidence of combined properties of heparin-coated ECC and aprotinin in reducing complement activation, coagulation, and fibrinolysis. We therefore recommend use of both together to achieve maximal reduction of blood activation during cardiopulmonary bypass for coronary artery operations.

Ten-year experience with surgical treatment of partial atrioventricular septal defect: Risk factors in the early postoperative period

Partial atrioventricular septal defects are electively repaired with good results. However, recent reports suggest that such repair is potentially a high-risk surgical procedure. Our aim was to determine the risk factors of adverse outcome early after surgical treatment of atrioventricular septal defects in our hospital. A retrospective study was done in 100 consecutive patients from 2 months to 50.6 years old (median 3.6 years) who underwent surgical correction between January 1984 and December 1993. An intermediate form of the lesion was noted in 31% of cases. Congestive heart failure occurred in 50% of cases. Preoperative left atrioventricular valve incompetence (moderate to severe) was present in 63% of patients. Severe abnormalities of left subvalvular apparatus were noted in 28% of patients. The cleft of the left atrioventricular valve was closed in 76% of cases. The study was done to determine risk factors associated with hospital mortality (13%), postoperative residual left atrioventricular valve incompetence (23%), and early reoperation (14%) within the first 30 postoperative days. Univariate analysis showed that age at the date of operation and cleft closure were not related to an early adverse outcome. A stepwise logistic regression with variables selected by univariate analysis identified infections and severe abnormalities of left subvalvular apparatus as predictive factors of early death (odds ratio, 28.07 and 6.18, respectively), preoperative left atrioventricular valve regurgitation as a predictive factor of residual postoperative left atrioventricular valve regurgitation (odds ratio, 5.34), and severe abnormalities of left subvalvular apparatus as a predictive factor of early reoperation (odds ratio, 5.27). These results emphasize the importance of the severity of the morphologic features of the left subvalvular apparatus, the occurrence of early postoperative infections, and the presence of residual left atrioventricular valve regurgitation as risk factors in the early period after surgical correction of partial atrioventricular septal defects.

Inflammatory response to cardiopulmonary bypass using two different types of heparin-coated extracorporeal circuits

Previous reports have highlighted the disparity in biocompatibility of two differently engineered heparin coatings during the cardiopulmonary bypass (CPB) procedure. The aim of this prospective study was to evaluate the impact of the difference in haemocompatibility provided by either the Duraflo II equipment or the Carmeda equipment in the terminal inflammatory response observed after coronary artery surgery. Thirty patients were randomly allocated to two groups to be operated on using either Duraflo II equipment (group I) or Carmeda equipment (group 2) for extracorporeal circulation (ECC). Initial inflammatory response was assessed by terminal complement complex activation (SC5b-9). The late inflammatory response observed in the postoperative period was assessed by measuring cytokine production (tumour factor necrosis (TNFα), interleukin IL-6, interleukin IL-8) and circulating concentrations of adhesion molecules (ELAM-1, ICAM-1). The release of SC5b-9 after CPB and after protamine administration was lower in group 2 than in group 1 (p = 0.0002 and p = 0.006, respectively). A significant production of cytokines was detected in both groups with peak values observed within the time range of 4-6 h after the start of CPB. However, no difference was observed between the groups except for the IL-8 level in group 2, which was lower 2 h after the start of CPB (p = 0.01). Plasma levels of adhesion molecules were similar in both groups within the investigation period. Although the Carmeda equipment was more effective in reducing complement activation, the late inflammatory response was similar using either the Duraflo II or Carmeda equipment for extracorporeal circulation as reflected by the changes of cytokine and circulating adhesion molecule levels.

Systemic microvascular shunting through hyperdynamic capillaries after acute physiological disturbances following cardiopulmonary bypass.

Previously we showed that cardiopulmonary bypass (CPB) during cardiac surgery is associated with reduced sublingual microcirculatory perfusion and oxygenation. It has been suggested that impaired microcirculatory perfusion may be paralleled by increased heterogeneity of flow in the microvascular bed, possibly leading to arteriovenous shunting. Here we investigated our hypothesis that acute hemodynamic disturbances during extracorporeal circulation indeed lead to microcirculatory heterogeneity with hyperdynamic capillary perfusion and reduced systemic oxygen extraction. In this single-center prospective observational study, patients undergoing cardiac surgery with (n = 18) or without (n = 13) CPB were included. Perioperative microcirculatory perfusion was assessed sublingually with sidestream darkfield imaging, and recordings were quantified for microcirculatory heterogeneity and hyperdynamic capillary perfusion. The relationship with hemodynamic and oxygenation parameters was analyzed. Microcirculatory heterogeneity index increased substantially after onset of CPB [0.5 (0.0-0.9) to 1.0 (0.3-1.3); P = 0.031] but not during off-pump surgery. Median capillary red blood cell (RBC) velocity increased intraoperatively in the CPB group only [1,600 (913-2,500 μm/s) vs. 380 (190-480 μm/s); P < 0.001], with 31% of capillaries supporting high RBC velocities (>2,000 μm/s). Hyperdynamic microcirculatory perfusion was associated with reduced arteriovenous oxygen difference and systemic oxygen consumption during and after CPB. The current study provides the first direct human evidence for a microvascular shunting phenomenon through hyperdynamic capillaries following acute physiological disturbances after onset of CPB. The hypothesis of impaired systemic oxygen offloading caused by hyperdynamic capillaries was supported by reduced blood arteriovenous oxygen difference and low systemic oxygen extraction associated with CPB.

Microcirculatory Perfusion Is Preserved During Off-Pump but Not On-Pump Cardiac Surgery

OBJECTIVE This study investigated the perioperative course of microcirculatory perfusion in off-pump compared with on-pump surgery. Additionally, the impact of changes in systemic hemodynamics, hematocrit, and body temperature was studied. DESIGN Prospective, nonrandomized, observational study. SETTING Tertiary university hospital. PARTICIPANTS Patients undergoing coronary artery bypass grafting with (n = 13) or without (n = 13) use of cardiopulmonary bypass. INTERVENTIONS Microcirculatory measurements were obtained at 5 time points ranging from induction of anesthesia to ICU admission. MEASUREMENTS AND MAIN RESULTS Microcirculatory recordings were performed with sublingual sidestream dark field imaging. Despite a comparable reduction in intraoperative blood pressure between groups, the perfused vessel density decreased more than 20% after onset of extracorporeal circulation but remained stable in the off-pump group. The reduction in microvascular perfusion in the on-pump group was further paralleled by decreased hematocrit and temperature. Although postbypass hematocrit levels and body temperature were restored to similar levels as in the off-pump group, the median microvascular flow index remained reduced after bypass (2.4 [2.3-2.7]) compared with baseline (2.8 [2.7-2.9]; p = 0.021). CONCLUSIONS Microcirculatory perfusion remained unaltered throughout off-pump surgery. In contrast, microvascular perfusion declined after initiation of cardiopulmonary bypass and did not recover in the early postoperative phase.

A combined approach for improving cardiopulmonary bypass in coronary artery surgery: a pilot study.

Background: This is a pilot study carried out to assess the feasibility and the clinical impact of a combined approach of cardiopulmonary bypass (CPB) with reduced anti-coagulation. Methods: We used a retrospective, non-randomized analysis of 45 consecutive patients undergoing coronary artery bypass using standard CPB with full anticoagulation (activated clotting time, ACT, > 450 s) (Group 1; n = 23) or closed, heparin-coated CPB with low anticoagulation (ACT> 250 s), precise heparin and protamine titration, controlled suction, and retrograde autologous prime (Group 2; n = 22). Results: Patients were similar except for a higher incidence of three-vessel disease in Group 2 (77.3% versus 47.8%; p < 0.03). Heparin was reduced by 41% in Group 2 and protamine by 56% ( p < 0.0001). Total postoperative blood loss was similar between Groups 1 and 2 (429 ± 149 versus 435 ± 168 ml, respectively). However, the operative hematocrit decrease was lower in Group 2 (-1.6± 7.5% versus -6.9± 4.8%; p = 0.007), although hemodilution was similar, as reflected by the blood protein level. The need for postoperative inotropic support was less frequent in Group 2 (36.4% versus 65.2%; p = 0.05). Within the subgroup of patients weaned from CPB without requiring inotropic support ( n = 35), the cardiac index dropped significantly in Group 1 ( p = 0.003) 6 h after the start of CPB, whereas it remained stable in Group 2 ( p = 0.92). Using multivariate analyses, Group 2 was found to be more protected than Group 1 against myocardial cellular injury ( p = 0.046) and need for postoperative inotropic support ( p = 0.014). Conclusion: The pejorative postoperative outcome in coronary artery surgery was attenuated through a combined approach aimed at improving CPB.