Opioid-Sparing Cardiac Anesthesia: Secondary Analysis of an Enhanced Recovery Program for Cardiac Surgery.

BACKGROUND: Cardiac anesthetics rely heavily on opioids, with the standard patient receiving between 70 and 105 morphine sulfate equivalents (MSE; 10-15 µg/kg of fentanyl). A central tenet of Enhanced Recovery Programs (ERP) is the use of multimodal analgesia. This study was performed to assess the association between nonopioid interventions employed as part of an ERP for cardiac surgery and intraoperative opioid administration. METHODS: This study represents a post hoc secondary analysis of data obtained from an institutional ERP for cardiac surgery. Consecutive patients undergoing cardiac surgery received 5 nonopioid interventions, including preoperative gabapentin and acetaminophen, intraoperative dexmedetomidine and ketamine infusions, and regional analgesia via serratus anterior plane block. The primary objective, the association between intraoperative opioid administration and the number of interventions provided, was assessed via a linear mixed-effects regression model. To assess the association between intraoperative opioid administration and postoperative outcomes, patients were stratified into high (>50 MSE) and low (≤50 MSE) opioids, 1:1 propensity matched based on 15 patients and procedure covariables and assessed for associations with postoperative outcomes of interest. To investigate the impact of further opioid restriction, ultralow (≤25 MSE) opioid participants were then identified, 1:3 propensity matched to high opioid patients, and similarly compared. RESULTS: A total of 451 patients were included in the overall analysis. Analysis of the primary objective revealed that intraoperative opioid administration was inversely related to the number of interventions employed (estimated -7.96 MSE per intervention, 95% confidence interval [CI], -9.82 to -6.10, P < .001). No differences were detected between low (n = 136) and high (n = 136) opioid patients in postoperative complications, postoperative pain scores, time to extubation, or length of stay. No differences were found in outcomes between ultralow (n = 63) and high (n = 132) opioid participants. CONCLUSIONS: Nonopioid interventions employed as part of an ERP for cardiac surgery were associated with a reduction of intraoperative opioid administration. Low and ultralow opioid use was not associated with significant differences in postoperative outcomes. These findings are hypothesis-generating, and future prospective studies are necessary to establish the role of opioid-sparing strategies in the setting of cardiac surgery.

Trends and Updates on Cardiopulmonary Bypass Setup in Pediatric Cardiac Surgery.

Perfusion strategies for cardiopulmonary bypass have direct consequences on pediatric cardiac surgery outcomes. However, inconsistent study results and a lack of uniform evidence-based guidelines for pediatric cardiopulmonary bypass management have led to considerable variability in perfusion practices among, and even within, institutions. Important aspects of cardiopulmonary bypass that can be optimized to improve clinical outcomes of pediatric patients undergoing cardiac surgery include extracorporeal circuit components, priming solutions, and additives. This review summarizes the current literature on circuit components and priming solution composition with an emphasis on crystalloid, colloid, and blood-based primes, as well as mannitol, bicarbonate, and calcium.

Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition.

We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the nonvisual G protein-coupled receptor melanopsin (Opsin 4; Opn4). Here we tested the hypothesis that nonvisual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G protein-coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2, as demonstrated with a proximity ligation assay. Light elicited an intensity-dependent relaxation of PAs preconstricted with phenylephrine (PE), with a maximum response between 400 and 460 nm (blue light). Wavelength-specific photorelaxation was attenuated in PAs from Opn4-/- mice and further reduced following shRNA-mediated knockdown of Opn3. Inhibition of GRK2 amplified the response and prevented physiological desensitization to repeated light exposure. Blue light also prevented PE-induced constriction in isolated PAs, decreased basal tone, ablated PE-induced single-cell contraction of PASMCs, and reversed PE-induced depolarization in PASMCs when GRK2 was inhibited. The photorelaxation response was modulated by soluble guanylyl cyclase but not by protein kinase G or nitric oxide. Most importantly, blue light induced significant vasorelaxation of PAs from rats with chronic pulmonary hypertension and effectively lowered pulmonary arterial pressure in isolated intact perfused rat lungs subjected to acute hypoxia. These findings show that functional Opn3 and Opn4 in PAs represent an endogenous "optogenetic system" that mediates photorelaxation in the pulmonary vasculature. Phototherapy in conjunction with GRK2 inhibition could therefore provide an alternative treatment strategy for pulmonary vasoconstrictive disorders.

Pulse wave travel distance as a novel marker of ventricular-arterial coupling.

Each stroke volume ejected by the heart is distributed along the arterial system as a pressure waveform. How far the front of the pressure waveform travels within the arterial system depends both on the pulse wave velocity (PWV) and the ejection time (ET). We tested the hypothesis that ET and PWV are coupled together, in order to produce a pulse wave travel distance (PWTD = PWV × ET) which would match the distance from the heart to the most distant site in the arterial system. The study was conducted in 11 healthy volunteers. We recorded lead II of the ECG along with pulse plethysmography at ear, finger and toe. The ET at the ear and pulse arrival time to each peripheral site were extracted. We then calculated PWV followed by PWTD for each location. Taken into account the individual subject variability PWTDToe in the supine position was 153 cm (95% CI 146-160 cm). It was not different from arterial pathway distance from the heart to the toe (D Toe 153 cm). The PWTDFinger and PWTDEar were longer than the distance from the heart to the finger and ear irrespective of body position. ETEar and PWVToe appear to be coupled in healthy subjects to produce a PWTD that is roughly equivalent to the arterial pathway distance to the toe. We propose that PWTD should be evaluated further to test its potential as a noninvasive parameter of ventricular-arterial coupling in subjects with cardiovascular diseases.

Validation of a Real-Time Minute-to-Minute Urine Output Monitor and the Feasibility of Its Clinical Use for Patients Undergoing Cardiac Surgery.

Acute kidney injury after cardiac surgery is associated with increased morbidity and mortality. Methods for measuring urine output in real time may better ensure renal perfusion perioperatively in contrast to the current standard of care where urine output is visually estimated after empiric epochs of time. In this study, we describe an accurate method for monitoring urine output continuously during cardiopulmonary bypass. This may provide a means for setting patient-specific targets for blood pressure and cardiopulmonary bypass flow as a potential strategy to reduce the risk for acute kidney injury.

Melanopsin mediates light-dependent relaxation in blood vessels.

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. ß-Adrenergic receptor kinase 1 (ßARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

The impact of posture on the cardiac depolarization and repolarization phases of the QT interval in healthy subjects.

BACKGROUND: Postural changes affect both heart rate and the QT interval. OBJECTIVE: To investigate the effects of postural changes on the depolarization and repolarization phases of the QT interval. METHODS: A three lead ECG from 12 healthy young volunteers was recorded in the standing, sitting and in the supine positions. For the purpose of this study, we defined the depolarization phase as the QRS complex plus the ST segment and the repolarization phase as the duration of the T wave. RESULTS: QTc did not change with changes in position. The ratio of the duration of the depolarization phase to the repolarization phase was higher in the supine position (0.98±0.13) compared to the standing position (0.83±0.17). CONCLUSIONS: The origin of the T wave moves closer to the QRS complex during standing compared to the supine position. The observed changes are mainly due to shortening of the ST segment during standing compared to supine position.

Oxidative stress and rheologic properties of stored red blood cells before and after transfusion to surgical patients.

BACKGROUND: The loss of structural and functional integrity of red blood cells (RBCs) during storage, collectively referred to as "storage lesion," has been implicated in reduced oxygen delivery after transfusion. RBCs are highly susceptible to oxidative damage from generation of reactive oxygen species by autoxidation of hemoglobin. Therefore, we examined whether increased oxidative stress (OS) in stored RBCs is associated with impaired cell membrane deformability before or after transfusion. STUDY DESIGN AND METHODS: Thirty-four patients undergoing multilevel spine fusion surgery were enrolled. OS in RBCs was assessed by the presence of fluorescent heme degradation products and methemoglobin, which were measured with fluorimetric and spectrophotometric methods, respectively. Deformability and aggregation were determined by ektacytometry in stored RBCs, autologous salvaged RBCs, and posttransfusion blood samples. RESULTS: OS in stored RBCs was significantly increased with longer storage (R = 0.54, p = 0.032) and significantly higher than that in fresh RBCs (9.1 ± 1.3 fluorescent arbitrary units vs. 7.7 ± 0.9 fluorescent arbitrary units, p < 0.001). Deformability decreased (R = -0.60, p = 0.009) with increasing storage duration. OS was elevated (p < 0.05) and deformability was decreased (p < 0.05) in postoperative blood from patients who had undergone moderate (≥4 RBC units) but not minimal or no transfusion. Neither the decrease in deformability of RBCs nor the aggregation changes were correlated with OS. CONCLUSIONS: Although stored RBCs show signs of increased OS and loss of cell membrane deformability, these changes were not directly correlated and were only evident after moderate but not lower dose transfusion in postoperative surgical patients. These findings suggest that factors other than OS may contribute to impaired rheology with stored RBCs in the clinical setting.

Morbidity and Mortality after High-dose Transfusion.

BACKGROUND: It is well recognized that increased transfusion volumes are associated with increased morbidity and mortality, but dose-response relations between high- and very-high-dose transfusion and clinical outcomes have not been described previously. In this study, the authors assessed (1) the dose-response relation over a wide range of transfusion volumes for morbidity and mortality and (2) other clinical predictors of adverse outcomes. METHODS: The authors retrospectively analyzed electronic medical records for 272,592 medical and surgical patients (excluding those with hematologic malignancies), 3,523 of whom received transfusion (10 or greater erythrocyte units throughout the hospital stay), to create dose-response curves for transfusion volumes and in-hospital morbidity and mortality. Prehospital comorbidities were assessed in a risk-adjusted manner to identify the correlation with clinical outcomes. RESULTS: For patients receiving high- or very-high-dose transfusion, infections and thrombotic events were four to five times more prevalent than renal, respiratory, and ischemic events. Mortality increased linearly over the entire dose range, with a 10% increase for each 10 units of erythrocytes transfused and 50% mortality after 50 erythrocyte units. Independent predictors of mortality were transfusion dose (odds ratio [OR], 1.037; 95% CI, 1.029 to 1.044), the Charlson comorbidity index (OR, 1.209; 95% CI, 1.141 to 1.276), and a history of congestive heart failure (OR, 1.482; 95% CI, 1.062 to 2.063). CONCLUSIONS: Patients receiving high- or very-high-dose transfusion are at especially high risk for hospital-acquired infections and thrombotic events. Mortality increased linearly over the entire dose range and exceeded 50% after 50 erythrocyte units.

The Impact of Surgery and Stored Red Blood Cell Transfusions on Nitric Oxide Homeostasis.

BACKGROUND: Cell-free hemoglobin (Hb) forms in stored red blood cells (RBCs) as a result of hemolysis. Studies suggest that this cell-free Hb may decrease nitric oxide (NO) bioavailability, potentially leading to endothelial dysfunction, vascular injury, and multiorgan dysfunction after transfusion. We tested the hypothesis that moderate doses of stored RBC transfusions increase cell-free Hb and decrease NO availability in postoperative surgical patients. METHODS: Twenty-six patients undergoing multilevel spine fusion surgery were studied. We compared those who received no stored RBCs (n = 9) with those who received moderate amounts (6.1 ± 3.0 units) of stored RBCs over 3 perioperative days (n = 17). Percent hemolysis (cell-free Hb), RBC-NO (heme-NO), and plasma nitrite and nitrate were measured in samples from the stored RBC bags and from patients' blood, before and after surgery. RESULTS: Posttransfusion hemolysis was increased approximately 3.5-fold over preoperative levels (P = 0.0002) in blood samples collected immediately after surgery but not on postoperative days 1 to 3. Decreases in both heme-NO (by approximately 50%) and plasma nitrite (by approximately 40%) occurred postoperatively, both in nontransfused patients (P = 0.036 and P = 0.026, respectively) and transfused patients (P = 0.0068 and P = 0.003, respectively) and returned to preoperative baseline levels by postoperative day 2 or 3. Postoperative plasma nitrite and nitrate were decreased significantly in both groups, and this change was slower to return to baseline in the transfused patients, suggesting that blood loss and hemodilution from crystalloid administration contribute to this finding. CONCLUSIONS: The decrease in NO metabolites occurred irrespective of stored RBC transfusions, suggesting this decrease may be related to blood loss during surgery and hemodilution rather than to scavenging of NO or inhibition of NO synthesis by stored RBC transfusions.

2,3-Diphosphoglycerate Concentrations in Autologous Salvaged Versus Stored Red Blood Cells and in Surgical Patients After Transfusion.

BACKGROUND: Stored red blood cells (RBCs) are deficient in 2,3-diphosphoglycerate (2,3-DPG), but it is unclear how autologous salvaged blood (ASB) compares with stored blood and how rapidly 2,3-DPG levels return to normal after transfusion. Therefore, we compared levels of 2,3-DPG in stored versus ASB RBCs and in patients' blood after transfusion. METHODS: Twenty-four patients undergoing multilevel spine fusion surgery were enrolled. We measured 2,3-DPG and the oxyhemoglobin dissociation curve (P50) in samples taken from the ASB and stored blood bags before transfusion and in blood samples drawn from patients before and after transfusion. RESULTS: The mean storage duration for stored RBCs was 24 ± 8 days. Compared with fresh RBCs, stored RBCs had decreased 2,3-DPG levels (by approximately 90%; P < 0.0001) and a decreased P50 (by approximately 30%; P < 0.0001). However, ASB RBCs did not exhibit these changes. The mean 2,3-DPG concentration decreased by approximately 20% (P < 0.05) in postoperative blood sampled from patients who received 1 to 3 stored RBC units and by approximately 30% (P < 0.01) in those who received ≥4 stored RBC units. 2,3-DPG was unchanged in patients who received no stored blood or ASB alone. After surgery, 2,3-DPG levels recovered gradually over 3 postoperative days in patients who received stored RBCs. CONCLUSIONS: Stored RBCs, but not ASB RBCs, have decreased levels of 2,3-DPG and a left-shift in the oxyhemoglobin dissociation curve. Postoperatively, 2,3-DPG levels remain below preoperative baseline levels for up to 3 postoperative days in patients who receive stored RBCs but are unchanged in those who receive only ASB RBCs.

Continuous Intraoperative Cefazolin Infusion May Reduce Surgical Site Infections During Cardiac Surgical Procedures: A Propensity-Matched Analysis.

OBJECTIVES: The authors sought to determine whether an institutional transition from intermittent to continuous dosing of intraoperative antibiotics in cardiac surgery affected surgical site infection (SSI) outcomes. DESIGN: A retrospective chart review utilizing propensity matching. SETTING: A single academic, tertiary care hospital. PARTICIPANTS: One thousand one hundred seventy-nine patients undergoing coronary artery bypass grafting (CABG) and/or cardiac valvular surgery between April 2013 and November 2014 who received perioperative cefazolin. INTERVENTIONS: By method of cefazolin administration, patients were divided into an "intermittent-dosing" (ID) group and a "continuous-infusion" (CI) group. MEASUREMENTS AND MAIN RESULTS: Of the 1,179 patients who underwent cardiac surgery during the study period, 1:1 propensity score matching yielded 399 patients in each group. Rates of diabetes (33.6% ID v 33.8% CI, p = 0.94), coronary artery bypass (62.3% v 61.4%, p = 0.66), and bilateral internal mammary artery harvesting (6.0% v 8.3%, p = 0.22) were similar between groups. SSIs occurred in more ID patients than CI patients (2.3% v 0.5%, p = 0.03). This difference was driven by decreases in extremity and conduit harvest site SSIs (1.8% v 0.3%, p = 0.03), as there were no episodes of mediastinitis, and superficial sternal SSI rates did not differ (0.5% v 0.3%, p = 0.56). There also were significantly fewer episodes of pneumonia in the CI group (6.0% v 2.3%, p = 0.008). Intensive care unit and total lengths of stay did not differ. Thirty-day mortality was 2.8% in both groups (p = 1.00). CONCLUSIONS: As compared to ID regimens, CI cefazolin infusion may reduce post-cardiac surgery infectious complications. Further study in larger patient populations is needed.

New insights provided by a comparison of impaired deformability with erythrocyte oxidative stress for sickle cell disease.

Sickle cell disease (SCD) is associated with increase in oxidative stress and irreversible membrane changes that originates from the instability and polymerization of deoxygenated hemoglobin S (HbS). The relationship between erythrocyte membrane changes as assessed by a decrease in deformability and oxidative stress as assessed by an increase in heme degradation was investigated. The erythrocyte deformability and heme degradation for 27 subjects with SCD and 7 with sickle trait were compared with normal healthy adults. Changes in both deformability and heme degradation increased in the order of control to trait to non-crisis SCD to crisis SCD resulting in a very significantly negative correlation between deformability and heme degradation. However, a quantitative analysis of the changes in deformability and heme degradation for these different groups of subjects indicated that sickle trait had a much smaller effect on deformability than on heme degradation, while crisis affects deformability to a greater extent than heme degradation. These findings provide insights into the relative contributions of erythrocyte oxidative stress and membrane damage during the progression of SCD providing a better understanding of the pathophysiology of SCD.

Nitroprusside inhibits calcium-induced impairment of red blood cell deformability.

BACKGROUND: Red blood cell (RBC) deformation is critical for microvascular perfusion and oxygen delivery to tissues. Abnormalities in RBC deformability have been observed in aging, sickle cell disease, diabetes, and preeclampsia. Although nitric oxide (NO) prevents decreases in RBC deformability, the underlying mechanism is unknown. STUDY DESIGN AND METHODS: As an experimental model, we used ionophore A23187-mediated calcium influx in RBCs to reduce their deformability and investigated the role of NO donor sodium nitroprusside (SNP) and KCa3.1 (Gardos) channel blockers on RBC deformability (measured as elongation index [EI] by microfluidic ektacytometry). RBC intracellular Ca(2+) and extracellular K(+) were measured by inductively coupled plasma mass spectrometry and potassium ion selective electrode, respectively. RESULTS: SNP treatment of RBCs blocked the Ca(2+) (approx. 10 µmol/L)-induced decrease in RBC deformability (EI 0.34 ± 0.02 vs. 0.09 ± 0.01, control vs. Ca(2+) loaded, p < 0.001; and EI 0.37 ± 0.02 vs. 0.30 ± 0.01, SNP vs. SNP plus Ca(2+) loaded) as well as Ca(2+) influx and K(+) efflux. The SNP effect was similar to that observed after pharmacologic blockade of the KCa3.1 channel (with charybdotoxin or extracellular medium containing isotonic K(+) concentration). In RBCs from KCa3.1(-/-) mice, 10 µmol/L Ca(2+) loading did not decrease cellular deformability. A preliminary attempt to address the molecular mechanism of SNP protection suggests the involvement of cell surface thiols. CONCLUSION: Our results suggest that nitroprusside treatment of RBCs may protect them from intracellular calcium increase-mediated stiffness, which may occur during microvascular perfusion in diseased states, as well as during RBC storage.

Impaired red blood cell deformability after transfusion of stored allogeneic blood but not autologous salvaged blood in cardiac surgery patients.

BACKGROUND: Both cardiopulmonary bypass (CPB) and red blood cell (RBC) storage are associated with detrimental changes in RBC structure and function that may adversely affect tissue oxygen delivery. We tested the hypothesis that in cardiac surgery patients, RBC deformability and aggregation are minimally affected by CPB with autologous salvaged blood alone but are negatively affected by the addition of stored allogeneic blood. METHODS: In this prospective cohort study, 32 patients undergoing cardiac surgery with CPB were divided into 3 groups by transfusion status: autologous salvaged RBCs alone (Auto; n = 12), autologous salvaged RBCs + minimal (<5 units) stored allogeneic RBCs (Auto+Allo min; n = 10), and autologous salvaged RBCs + moderate (≥5 units) stored allogeneic RBCs (Auto+Allo mod; n = 10). Ektacytometry was used to measure RBC elongation index (deformability) and critical shear stress (aggregation) before, during, and for 3 days after surgery. RESULTS: In the Auto group, RBC elongation index did not change significantly from the preoperative baseline. In the Auto+Allo min group, mean elongation index decreased from 32.31 ± 0.02 (baseline) to 30.47 ± 0.02 (nadir on postoperative day 1) (P = 0.003, representing a 6% change). In the Auto+Allo mod group, mean elongation index decreased from 32.7 ± 0.02 (baseline) to 28.14 ± 0.01 (nadir on postoperative day 1) (P = 0.0001, representing a 14% change). Deformability then dose-dependently recovered toward baseline over the first 3 postoperative days. Changes in aggregation were unrelated to transfusion (no difference among groups). For the 3 groups combined, mean critical shear stress decreased from 359 ± 174 mPa to 170 ± 141 mPa (P = 0.01, representing a 54% change), with the nadir at the end of surgery and returned to baseline by postoperative day 1. CONCLUSIONS: In cardiac surgery patients, transfusion with stored allogeneic RBCs, but not autologous salvaged RBCs, is associated with a decrease in RBC cell membrane deformability that is dose-dependent and may persist beyond 3 postoperative days. These findings suggest that autologous salvaged RBCs may be of higher quality than stored RBCs, since the latter are subject to the so-called storage lesions.

Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels.

RATIONALE: Nitric oxide, the classic endothelium-derived relaxing factor (EDRF), acts through cyclic GMP and calcium without notably affecting membrane potential. A major component of EDRF activity derives from hyperpolarization and is termed endothelium-derived hyperpolarizing factor (EDHF). Hydrogen sulfide (H(2)S) is a prominent EDRF, since mice lacking its biosynthetic enzyme, cystathionine γ-lyase (CSE), display pronounced hypertension with deficient vasorelaxant responses to acetylcholine. OBJECTIVE: The purpose of this study was to determine if H(2)S is a major physiological EDHF. METHODS AND RESULTS: We now show that H(2)S is a major EDHF because in blood vessels of CSE-deleted mice, hyperpolarization is virtually abolished. H(2)S acts by covalently modifying (sulfhydrating) the ATP-sensitive potassium channel, as mutating the site of sulfhydration prevents H(2)S-elicited hyperpolarization. The endothelial intermediate conductance (IK(Ca)) and small conductance (SK(Ca)) potassium channels mediate in part the effects of H(2)S, as selective IK(Ca) and SK(Ca) channel inhibitors, charybdotoxin and apamin, inhibit glibenclamide-insensitive, H(2)S-induced vasorelaxation. CONCLUSIONS: H(2)S is a major EDHF that causes vascular endothelial and smooth muscle cell hyperpolarization and vasorelaxation by activating the ATP-sensitive, intermediate conductance and small conductance potassium channels through cysteine S-sulfhydration. Because EDHF activity is a principal determinant of vasorelaxation in numerous vascular beds, drugs influencing H(2)S biosynthesis offer therapeutic potential.

Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage duration.

BACKGROUND: Erythrocyte cell membranes undergo morphologic changes during storage, but it is unclear whether these changes are reversible. We assessed erythrocyte cell membrane deformability in patients before and after transfusion to determine the effects of storage duration and whether changes in deformability are reversible after transfusion. METHODS: Sixteen patients undergoing posterior spinal fusion surgery were studied. Erythrocyte deformability was compared between those who required moderate transfusion (≥ 5 units erythrocytes) and those who received minimal transfusion (0-4 units erythrocytes). Deformability was measured in samples drawn directly from the blood storage bags before transfusion and in samples drawn from patients before and after transfusion (over 3 postoperative days). In samples taken from the blood storage bags, we compared deformability of erythrocytes stored for a long duration (≥ 21 days), those stored for a shorter duration (<21 days), and cell-salvaged erythrocytes. Deformability was assessed quantitatively using the elongation index (EI) measured by ektacytometry, a method that determines the ability for the cell to elongate when exposed to shear stress. RESULTS: Erythrocyte deformability was significantly decreased from the preoperative baseline in patients after moderate transfusion (EI decreased by 12% ± 4% to 20% ± 6%; P = 0.03) but not after minimal transfusion (EI decreased by 3% ± 1% to 4% ± 1%; P = 0.68). These changes did not reverse over 3 postoperative days. Deformability was significantly less in erythrocytes stored for ≥ 21 days (EI = 0.28 ± 0.02) than in those stored for <21 days (EI = 0.33 ± 0.02; P = 0.001) or those drawn from patients preoperatively (EI = 0.33 ± 0.02; P = 0.001). Cell-salvaged erythrocytes had intermediate deformability (EI = 0.30 ± 0.03) that was greater than that of erythrocytes stored ≥ 21 days (P = 0.047), but less than that of erythrocytes stored <21 days (P = 0.03). CONCLUSIONS: The findings demonstrate that increased duration of erythrocyte storage is associated with decreased cell membrane deformability and that these changes are not readily reversible after transfusion.

Preoperative renin-angiotensin system inhibitors protect renal function in aging patients undergoing cardiac surgery.

BACKGROUND: Renal failure (RF) represents a major postoperative complication for elderly patients undergoing cardiac surgery. This observational cohort study examines effects of preoperative use of renin-angiotensin system (RAS) inhibitors on postoperative renal failure in aging patients undergoing cardiac surgery. METHODS AND RESULTS: We retrospectively analyzed a cohort of 1287 patients who underwent cardiac surgery at this institution (2003-2007). The patients included were ≥65 years old, scheduled for elective cardiac surgery, and without preexisting RF (defined by the criteria of the Society of Thoracic Surgeons as described in Method). Of all patients evaluated, 346 patients met the inclusion criteria and were divided into two groups: using (n = 122) or not using (n = 224) preoperative RAS inhibitors. A comparison of the two groups showed no significant differences in baseline parameters, including creatinine clearance, body mass index, history of diabetes and smoking, preoperative medicines (except that more patients with RAS inhibitors had a history of hypertension or congestive heart failure, fewer RAS inhibitor patients had chronic lung disease), in intraoperative perfusion and aortic cross-clamp time, and in postoperative complications and 30-d mortality. Multivariate logistic regression analysis demonstrated, however, that preoperative RAS inhibitors significantly and independently reduced the incidence of postoperative RF in the patients undergoing cardiac surgery compared with those not taking RAS inhibitors: 1.6% versus 7.6%, yielding an odds ratio of 0.19 (95 % CI 0.04-0.84, P = 0.029). CONCLUSIONS: Preoperative RAS inhibitors may have significant renoprotective effects for aging patients undergoing elective cardiac surgery.