A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair

IntroductionGoal-directed therapy (GDT) has been shown in numerous studies to decrease perioperative morbidity and mortality. The mechanism of benefit of GDT, however, has not been clearly elucidated. Targeted resuscitation of the vascular endothelium with GDT might alter the postoperative inflammatory response and be responsible for the decreased complications with this therapy.MethodsThis trial was registered at ClinicalTrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT01681251","term_id":"NCT01681251"}}NCT01681251. Forty patients undergoing elective open repair of their abdominal aortic aneurysm, 18 years of age and older, were randomized to an interventional arm with GDT targeting stroke volume variation with an arterial pulse contour cardiac output monitor, or control, where fluid therapy was administered at the discretion of the attending anesthesiologist. We measured levels of several inflammatory cytokines (C-reactive protein, Pentraxin 3, suppressor of tumorgenicity--2, interleukin-1 receptor antagonist, and tumor necrosis factor receptor-III) preoperatively and at several postoperative time points to determine if there was a difference in inflammatory response. We also assessed each group for a composite of postoperative complications.ResultsTwenty patients were randomized to GDT and twenty were randomized to control. Length of stay was not different between groups. Intervention patients received less crystalloid and more colloid. At the end of the study, intervention patients had a higher cardiac index (3.4 ± 0.5 vs. 2.5 ± 0.7 l/minute per m², p < 0.01) and stroke volume index (50.1 ± 7.4 vs. 38.1 ± 9.8 ml/m², p < 0.01) than controls. There were significantly fewer complications in the intervention than control group (28 vs. 12, p = 0.02). The length of hospital and ICU stay did not differ between groups. There was no difference in the levels of inflammatory cytokines between groups.ConclusionsDespite being associated with fewer complications and improved hemodynamics, there was no difference in the inflammatory response of patients treated with GDT. This suggests that the clinical benefit of GDT occurs in spite of a similar inflammatory burden. Further work needs to be performed to delineate the mechanism of benefit of GDT.

Trial registration

ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01681251","term_id":"NCT01681251"}}NCT01681251. Registered 18 May 2011.     

Short-Term Memory During Stage-2 Sleep

A recently-proposed model of dream recall phenomena (Koulack & Goodenough, 1976) assumes a short-term memory store which functions during sleep, and from which either dreams or externally-delivered stimuli can be retrieved if the subject is awakened during the life of the short-term trace. To test this assumption, two experiments were designed to examine short-term memory for auditory stimuli over intervals of uninterrupted stage-2 sleep. A random series of single-digit numbers was presented at the rate of one every 30 sec throughout the night, at an intensity slightly above normal conversational levels. Subjects habituated to the sound and did not awaken spontaneously. Experimental awakenings took place either at 1 sec (Experiment 1) or at 1, 5, or 10 sec (Experiment 2) after selected target stimuli, and the subjects were asked to recall which number they had heard. Significant recall was obtained over intervals of up to 10 sec, and the likelihood of recall was inversely related to reaction times to the awakening stimulus. Repeating the target numbers at 30-sec intervals increased EEG alpha activity and K-complex amplitude, suggesting that some form of trace persists for at least 30 sec.     

EFFECTS OF A STRESSFUL PRESLEEP EXPERIENCE ON ELECTROENCEPHALOGRAPHRECORDED SLEEP

The effects on experimentally uninterrupted sleep of two films, one psychologically stressful and the other neutral, both seen just before bed, were studied in 12 male Ss on 2 nights according to a balanced design. EEG and electro-ocu-logram recordings were made of the first 6 hours of sleep. The stress film significantly increased the number of awakenings associated with rapid eye-movement periods (REMPs), but not that of non-REM sleep awakenings, as well as the proportion of REMPs terminated by spontaneous awakenings. It furthermore increased the frequency of REMs (REM density) during REMPs. These results suggest that the stress film produced a specific REM sleep disturbing effect via anxiety which carried over into the Ss’ sleep and dreams, and that it increased REM density secondary to drive enhancement.     

Upper extremity complications in patients with chronic renal failure receiving haemodialysis

Limited data are available about disability associated with upper extremity complications in patients who receive haemodialysis for end-stage renal disease. In this study of 123 patients receiving haemodialysis, the mean Disabilities of the Arm, Shoulder and Hand (DASH) score was 31 ± 22 points, indicating markedly greater disability than in a normal population. Dupuytren's contracture was the most frequent deformity. Brachial, radial and ulnar pulses were present in most upper limbs, but 14 (14%) of 102 patients had poor arterial perfusion pressures. Diabetic patients had residual or complete loss of protective sensation more frequently than nondiabetic patients. Motor testing with the index finger abduction and fifth finger flexion tests showed a significantly greater frequency of weakness in diabetic than nondiabetic patients. In summary, upper extremity disability was noted in haemodialysis patients, including loss of protective sensation and motor strength, both in diabetic and nondiabetic subjects.     

The Effects of Stress Films on Dream Affect and on Respiration and Eye-Movement Activity During Rapid-Eye-Movement Sleep

The effects of stress on the affective content of dreams and on rapid-eye-movement (REM) period eye-movement activity and respiration were studied. The experiment was also designed to examine the similarity between walking and sleeping states in the respiratory correlates of emotion. Sleep records and dream reports were collected following the viewing of stress and neutral films. The stress films significantly increased dream anxiety and also increased REM-period respiratory irregularity among those Ss who, in the walking state, showed irregular breath patterns in response to stressful film scenes. Some evidence was also found that dream affect is related to RFM-period respiratory irregularity among the Ss who are walking responders. These data are interpreted as supporting the hypothesized congruence between the waking und dream states in The relationship between affect and breathing irregularity.     

Development of a mouse aortic transplant model of chronic rejection

Chronic rejection is the most common cause of late graft failure after solid organ transplantation. A model of chronic rejection, the rat aortic allograft, has histologic features that parallel those in the vessels of human transplanted organs. However, the molecular tools required to dissect the immunology of chronic rejection are unavailable in the rat. We developed aortic transplantation in the mouse as a new model of chronic rejection. This will allow the use of the diversity of recombinant cytokines and monoclonal antibodies available for the mouse and its well-defined genetics to investigate chronic rejection in greater detail. We describe the perioperative care and surgical technique for the model in which a 1 cm segment of donor thoracic aorta was used to replace a section of recipient abdominal aorta below the renal arteries and above the aortic bifurcation. Mortality rates were initially high (70%) due to thrombosis and shock. Changes in technique and operator facility resulted in a high rate of success (75%). After 192 operations, the current success rate is >80%. Mice free from complications at 12 hrs postop had indefinite survival, and after 2 months the typical vascular lesion of chronic rejection was present. This new model of chronic rejection will be a valuable tool to study the molecular immunology and genetics of chronic rejection. © 1995 Wiley-Liss, Inc.     

Revascularization for peripheral vascular disease in Aboriginal and non-Aboriginal patients

BACKGROUND: Canadian Aboriginal subjects have a higher prevalence of diabetes, renal disease, and lower extremity amputation than non-Aboriginal subjects. However, limited information is available about patient outcomes for arterial bypass surgery in Canadian Aboriginal compared with non-Aboriginal subjects. METHODS: A retrospective study of all patients undergoing revascularization for peripheral vascular disease at a tertiary care referral center was performed. RESULTS: A total of 828 procedures were performed on 678 patients between 1995 and 2002: 108 (13%) procedures on 84 (12%) Aboriginal patients and 720 (87%) procedures on 594 (88%) non-Aboriginal patients. Aboriginal patients had a higher prevalence of diabetes, chronic renal failure, and end-stage renal disease than non-Aboriginal patients. Aboriginal patients presented with more serious complications (gangrene [Aboriginal, 63 [58%] of 108 patients; non-Aboriginal, 112 [16%] of 720 patients; P < .0001] and nonhealing ulcer [Aboriginal, 29 [27%] of 108 patients; non-Aboriginal, 131 [18%] of 720 patients; P < .05]) and required urgent or emergency revascularization (Aboriginal, 47 [49%] of 95 patients; non-Aboriginal, 228 [36%] of 634 patients; P < .02) more frequently than non-Aboriginal patients. The 60-month patient mortality was similar for both groups (Aboriginal, 20 [24%] of 84 patients; non-Aboriginal, 160 [27%] of 594 patients; not significant), but Aboriginal patients had loss of limb more frequently (Aboriginal, 19 [18%] of 108 patients; non-Aboriginal, 62 [9%] of 720 patients; P < .0001) and had loss of primary graft patency more frequently (Aboriginal, 39 [36%] of 108 patients; non-Aboriginal, 155 [22%] of 720 patients; P < .0001) than non-Aboriginal patients. CONCLUSIONS: Canadian Aboriginal subjects had worse outcomes with revascularization than non-Aboriginal subjects, but ethnicity and diabetes were not independent risk factors for poor outcome. Multivariate analysis showed that the poor outcomes in mortality, limb salvage, and primary graft patency among Aboriginal patients undergoing revascularization may be attributed to renal disease and a more advanced mode of presentation of peripheral vascular disease complications at the time of intervention.     

Lactate flux during carotid endarterectomy under general anesthesia: correlation with various point-of-care monitors

Purpose

The ability to assess the brain-at-risk during carotid endarterectomy (CEA) under general anesthesia remains a major clinical problem. Point-of-care monitoring can potentially dictate changes to management intraoperatively. In this observational study, we examined the correlation between a series of point-of-care monitors and lactate flux during CEA.

Methods

Both neurosurgeons and vascular surgeons participated in the study. The patients underwent arterial-jugular venous blood sampling for oxygen, carbon dioxide, glucose, and lactate, n = 26; bispectral index (BIS) monitoring ipsilateral to side of surgery, n = 26; raw and processed electroencephalogram (EEG), n = 22; and bi-frontal cerebral oximetry using the Fore-Sight monitor, n = 20.

Results

One patient experienced a new neurological deficit when assessed at 24 hr following surgery. Lactate flux into the brain was correlated with the greatest decrease in cerebral oximetry with carotid cross-clamping; lactate efflux was correlated with the least. The most noticeable changes in processed EEG (density spectral analysis) were also seen with lactate influx, but at a slower time resolution than cerebral oximetry. Loss of autoregulatory behaviour was demonstrated with lactate influx; however, no correlation was seen between lactate flux and BIS monitoring.

Conclusion

There was a correlation between cerebral oximetry and lactate flux during carotid cross-clamping. The Fore-Sight monitor may be of value as a point-of-care monitor during CEA under general anesthesia. A novel finding of this study is lactate flux into the brain in the presence of a large difference in cerebral oxygenation during cross-clamping of the carotid artery. Registered at clinicaltrials.gov: NCT000737334.