The association between duration of storage of transfused red blood cells and morbidity and mortality after reoperative cardiac surgery.

Red blood cells (RBCs) undergo numerous changes during storage; however, the clinical relevance of these storage "lesions" is unclear. We hypothesized that the duration of storage of transfused RBCs is associated with mortality after repeat sternotomy for cardiac surgery, because these patients are at high risk for both RBC transfusion and adverse outcome. We retrospectively analyzed 434 patients who underwent repeat median sternotomy for coronary artery bypass graft or valve surgery and who received allogeneic RBCs. Three-hundred-twenty-one (74%) patients met the criteria for eligibility. After adjusting for the effects of confounders and the total number of RBC transfusions, the duration of storage of the oldest RBC unit transfused was found to be associated with both in-hospital mortality (Cox proportional hazard ratio (HR) = 1.151; P < 0.0001) and out-of-hospital mortality (HR = 1.116; P < 0.0001). The mean duration of storage of transfused RBCs was also an independent predictor of in-hospital mortality (HR = 1.036; P < 0.0001). Independent associations between the duration of storage of transfused RBCs and acute renal dysfunction and intensive care unit and hospital length of stay were also observed. The duration of storage of RBCs is associated with adverse outcome after repeat sternotomy for cardiac surgery. The clinical significance of this finding should be investigated in a large, randomized, blinded clinical trial.

A randomized, double-blind, placebo-controlled study assessing the anti-inflammatory effects of ketamine in cardiac surgical patients.

OBJECTIVE: To determine whether ketamine administration affects markers of inflammation in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate differences between 2 low-dose ketamine regimens. DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: Single-center university hospital. PARTICIPANTS: Patients undergoing cardiac surgery with CPB. INTERVENTION: Patients (n = 50) were randomized to 1 of 3 groups: ketamine, 0.25 mg/kg (n = 15); ketamine, 0.5 mg/kg (n = 18);or placebo (n = 17) in a double-blind manner at the time of induction of general anesthesia. MEASUREMENTS AND MAIN RESULTS: Serum C-reactive protein (CRP) and interleukin (IL)-6, IL-8, and IL-10 were measured at baseline, on intensive care unit (ICU) arrival, and on the first postoperative day (POD 1). Both ketamine doses decreased the serum IL-6 response at ICU arrival and POD 1 compared with placebo (p < 0.05). CRP was lower in the 0.5-mg/kg group than placebo on POD 1 (p = 0.003). IL-10 was lower in the ketamine groups (p = 0.01) at POD 1 compared with placebo; IL-8 levels were not affected by ketamine. Mean arterial pressure and systemic vascular resistance were higher at the end of surgery, arrival in the ICU, and POD 1 in the ketamine groups (p < 0.05). CONCLUSION: Low-dose ketamine (0.5 mg/kg) attenuates increases in CRP, IL-6, and IL-10 while decreasing vasodilatation after CPB.

Comparison of intracarotid anesthetics for EEG silence.

The goal of this study was to compare systemic and cerebrovascular effects of three anesthetic drugs (etomidate, thiopental, and propofol) when delivered by intracarotid and intravenous routes in doses that produce electrocerebral silence (electroencephalography [EEG]). EEG activity, mean arterial pressure (MAP), and laser Doppler flow as a proxy of cerebral blood flow (CBF) of 24 anesthetized New Zealand white rabbits were continuously recorded. Data were compared at three timepoints: baseline, during EEG silence, and after recovery of EEG activity. Drugs were randomly injected via the carotid artery to produce 10 minutes of EEG silence. After 30 minutes of rest, intravenous boluses of the same drug were injected to achieve 10 minutes of EEG silence. During EEG silence, transient hypotension was seen with intracarotid propofol, but there was no decrease in CBF. MAP and CBF did not decrease with either intracarotid etomidate or thiopental during EEG silence. Intracarotid/intravenous dose ratio of propofol (26%+/-22%; n=8, P<0.02) was much higher than that of etomidate and thiopental (14%+/-2% and 19%+/-11%, respectively; NS). Collectively, these results suggest intracarotid etomidate and thiopental are more useful than propofol in producing EEG silence because they offer better dose advantage and are less likely to impair cerebral or systemic hemodynamics.

Cerebral blood flow affects dose requirements of intracarotid propofol for electrocerebral silence.

BACKGROUND: The authors hypothesized that cerebral blood flow (CBF) changes will affect the dose of intracarotid propofol required to produce electrocerebral silence. METHODS: The authors tested their hypothesis on New Zealand White rabbits. The first group of 9 animals received intracarotid propofol during (1) normoventilation, (2) hyperventilation, and (3) hypoventilation. The second group of 14 animals received intracarotid propofol with or without concurrent intraarterial verapamil, a potent cerebral vasodilator. The third group of 8 animals received bolus injection of propofol during normotension, during severe cerebral hypoperfusion, and after hemodynamic recovery. RESULTS: In the first group, there was a linear correlation between the dose of intracarotid propofol and percent change (%Delta) in CBF from the baseline due to changes in the minute ventilation, Total Dose (y) = 0.17 + 0.012 * %Delta CBF (x), n = 27, r = 0.76. In the second group, the dose of propofol was also a function of CBF change after verapamil, Total Dose (y) = 0.98 + 0.1 * %Delta CBF (x), n = 14, r = 0.75. In the third group, the duration of electrocerebral silence after intracarotid propofol (3 mg) was significantly increased with concurrent cerebral hypoperfusion compared with prehypoperfusion and posthypoperfusion values (141 +/- 38 vs. 19 +/- 24 and 16 +/- 12 s, respectively, P < 0.0001). CONCLUSIONS: The authors conclude that CBF affects the dose requirements of intracarotid propofol required to produce electrocerebral silence. Furthermore, the manipulation of CBF might be a useful tool to enhance the efficacy of intracarotid drugs.

Nitric oxide post-transcriptionally up-regulates LPS-induced IL-8 expression through p38 MAPK activation.

Nitric oxide (NO(.-)) contributes to vascular collapse in septic shock and regulates inflammation. Here, we demonstrate in lipopolysaccharide (LPS)-stimulated human THP-1 cells and monocytes that NO(.-) regulates interleukin (IL)-8 and tumor necrosis factor alpha (TNF-alpha) by distinct mechanisms. Dibutyryl-cyclic guanosine 5'-monophosphate (cGMP) failed to simulate NO(.-)-induced increases in TNF-alpha or IL-8 production. In contrast, dibutyryl-cyclic adenosine monophosphate blocked NO(.-)-induced production of TNF-alpha (P=0.009) but not IL-8. NO(.-) increased IL-8 (5.7-fold at 4 h; P=0.04) and TNF-alpha mRNA levels (2.2-fold at 4 h; P=0.037). However, nuclear run-on assays demonstrated that IL-8 transcription was slightly decreased by NO(.-) (P=0.08), and TNF-alpha was increased (P=0.012). Likewise, NO(.-) had no effect on IL-8 promoter activity (P=0.84) as measured by reporter gene assay. In THP-1 cells and human primary monocytes treated with actinomycin D, NO(.-) had no effect on TNF-alpha mRNA stability (P>0.3 for both cell types) but significantly stabilized IL-8 mRNA (P=0.001 for both cell types). Because of its role in mRNA stabilization, the p38 mitogen-activated protein kinase (MAPK) pathway was examined and found to be activated by NO(.-) in LPS-treated THP-1 cells and human monocytes. Further, SB202190, a p38 MAPK inhibitor, was shown to block NO(.-)-induced stabilization of IL-8 mRNA (P<0.02 for both cell types). Thus, NO(.-) regulates IL-8 but not TNF-alpha post-transcriptionally. IL-8 mRNA stabilization by NO(.-) is independent of cGMP and at least partially dependent on p38 MAPK activation.

Electrocerebral silence by intracarotid anesthetics does not affect early hyperemia after transient cerebral ischemia in rabbits.

UNLABELLED: Evidence suggests that early postischemic hyperemia is mediated by both neurological and vascular mechanisms. We hypothesized that if neuronal activity were primarily responsible for reperfusion hyperemia, then electrocerebral silence induced by intracarotid anesthetics (propofol and pentothal) would attenuate the hyperemic response. New Zealand white rabbits were subjected to 10 min of cerebral ischemia using bilateral carotid occlusion and systemic hypotension. Subsequently, carotid occlusion was released, and the mean arterial blood pressure was increased to baseline values. In the control group, intracarotid saline was periodically injected during reperfusion. In the treatment groups, intracarotid propofol or thiopental was administered to maintain electrocerebral silence for 10 min. Physiological data were measured at baseline, during ischemia, and at reperfusion. Satisfactory data were available for 16 of 19 rabbits. Mean arterial blood pressure, end-tidal CO(2), and cerebral blood flows decreased significantly in both groups during carotid occlusion. During early reperfusion, a similar percent increase in cerebral blood flow from baseline values was observed in all 3 groups (192% +/- 76%, 218% +/- 84%, and 185% +/- 101% for saline, propofol, and pentothal, respectively). These results suggest that suppression of neuronal activity during reperfusion does not affect early hyperemia after transient cerebral ischemia. IMPLICATIONS: Intracarotid injection of anesthetic drugs in doses that are sufficient to produce electrocerebral silence do not obtund early cerebral hyperemia after transient cerebral ischemia. This suggests that vascular, not neuronal mechanisms, are primarily responsible for early postischemic cerebral hyperperfusion.