Lysophosphatidic Acid Reduces Microregional Oxygen Supply/Consumption Balance after Cerebral Ischemia-Reperfusion.

BACKGROUND: Lysophosphatidic acid (LPA) is a small phospholipid-signaling molecule, which can alter responses to stress in the central nervous system. OBJECTIVE: We hypothesized that exogenous LPA would increase the size of infarct and reduce microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. METHODS: This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1 h and reperfusion for 2 h with or without LPA (1 mg/kg, at 30, 60, and 90 min after reperfusion). Regional cerebral blood flow was determined using a C14-iodoantipyrine autoradiographic technique. Regional small-vessel (20-60 µm in diameter) arterial and venous oxygen saturations were determined microspectrophotometrically. RESULTS: There were no significant hemodynamic or arterial blood gas differences between groups. The control ischemic-reperfused cortex had a similar O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex with many areas of low O2 saturation (43 of 80 veins with O2 saturation below 50%). LPA did not significantly alter cerebral blood flow, but it did significantly increase O2 extraction and consumption of the ischemic-reperfused region. It also significantly increased the number of small veins with low O2 saturations in the reperfused region (76 of 80 veins with O2 saturation below 50%). This was associated with a significantly increased cortical infarct size after LPA administration (11.4 ± 0.5% control vs. 16.4 ± 0.6% LPA). CONCLUSION: This suggests that LPA reduces cell survival and that it is associated with an increase in the number of small microregions with reduced local oxygen balance after cerebral ischemia-reperfusion.

Paravertebral Nerve Block With Liposomal Bupivacaine for Pain Control Following Video-Assisted Thoracoscopic Surgery and Thoracotomy.

BACKGROUND: Some surgeons have adopted the use of video-assisted thoracoscopic surgery (VATS) or robotic surgery to perform resections for lung cancer. VATS is associated with less pain and a decrease in pulmonary complications compared with open thoracotomies. Long-acting liposomal bupivacaine (LB) intercostal nerve blocks are reported to provide superior pain relief compared with epidural catheters in the first 3 d after a thoracotomy. This study examined whether LB improves pain after VATS and if it provides effective analgesia after a thoracotomy. MATERIALS AND METHODS: A retrospective review was performed on 151 consecutive patients undergoing a VATS or thoracotomy who received paravertebral nerve blocks. VATS patients received paravertebral nerve blocks with LB (VATS-LB) or 0.25% bupivacaine with epinephrine (BE; VATS-BE). Thoracotomy patients received paravertebral nerve blocks via LB injections. Pain scores, narcotic utilization, complications, and hospital length of stay were examined. RESULTS: Fifty patients underwent a VATS-LB, 53 underwent a VATS-BE, and 32 underwent a thoracotomy. Thoracotomy and VATS-LB patients had pain scores lower than VATS-BE patients in the first 48 h after surgery (P < 0.004). Opioid use was not significantly different between the thoracotomy and VATS-LB patients throughout the first 2 wk postoperatively. CONCLUSIONS: LB paravertebral blocks significantly improve postoperative pain in comparison with 0.25% BE blocks in VATS patients. LB paravertebral blocks also provide effective analgesia in patients undergoing thoracotomies.

Lysophosphatidic acid increased infarct size in the early stage of cerebral ischemia-reperfusion with increased BBB permeability.

BACKGROUND: We investigated whether exogenous lysophosphatidic acid (LPA), a phospholipid extracellular signaling molecule, would increase infarct size and blood-brain barrier (BBB) disruption during the early stage of cerebral ischemia-reperfusion, and whether it works through Akt-mTOR-S6K1 intracellular signaling. MATERIAL AND METHODS: Rats were given either vehicle or LPA 1 mg/kg iv three times during reperfusion after one hour of middle cerebral artery (MCA) occlusion. In another group, prior to administration of LPA, 30 mg/kg of PF-4708671, an S6K1 inhibitor, was injected. After one hour of MCA occlusion and two hours of reperfusion the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid and the volume of 3H-dextran distribution were determined to measure the degree of BBB disruption. At the same time, the size of infarct was determined and western blot analysis was performed to determine the levels of phosphorylated Akt (p-Akt) and phosphorylated S6 (pS6). RESULTS: LPA increased the Ki in the ischemic-reperfused cortex (+43%) when compared with Control rats and PF-4708671 pretreatment prevented the increase of Ki by LPA. LPA increased the percentage of cortical infarct out of total cortical area (+36%) and PF-4708671 pretreatment prevented the increase of the infarct size. Exogenous LPA did not significantly change the levels of p-Akt as well as pS6 in the ischemic-reperfused cortex. CONCLUSION: Our data demonstrate that the increase in BBB disruption could be one of the reasons of the increased infarct size by LPA. S6K1 may not be the major target of LPA. A decrease of LPA during early cerebral ischemia-reperfusion might be beneficial for neuronal survival.

Costs and outcomes after cardiac surgery in patients refusing transfusion compared with those who do not: a case-matched study.

BACKGROUND: Although numerous studies have demonstrated the feasibility of cardiac surgery for blood refusal patients, few studies match to controls, and fewer examine cost. This historical cohort study aims to compare costs and outcomes after cardiac surgery in Jehovah's Witness patients who refuse blood transfusion with a group of matched patients accepting transfusion. STUDY DESIGN AND METHODS: A retrospective database review was performed to find all patients having cardiac surgery who refused blood products from January 2005 to July 2012 at Duke University Medical Center. These 45 patients were closely matched 1:2 with controls who accepted transfusion based on characteristics likely to influence transfusion. Cost from day of surgery to hospital discharge and other outcome data (length of stay [LOS], discharge hemoglobin [Hb], acute kidney injury) were analyzed retrospectively. RESULTS: Forty-five Witnesses having cardiac surgery were temporally matched to two controls having the same surgery. Median euroSCORE was the same in both groups (6.0, p = 0.9981). In the matched-pairs comparison of cost, there was no significant difference in total cost for Witnesses and controls. There was no difference in intensive care unit LOS (median, 1 day, both groups) or total LOS (median, 9 days for Witnesses vs. 7 days for controls). Mean Hb at discharge was higher in Witnesses than in controls (11.7 g/dL vs. 9.8 g/dL, p < 0.001). Thirty-day mortality was zero in both groups. CONCLUSION: Utilizing applicable blood conservation measures, cardiac surgery may be performed with similar outcomes and cost from day of surgery to discharge compared to controls in select patients without blood transfusion.

The Optimal Angle of Head Rotation for Internal Jugular Cannulation as Determined by Ultrasound Evaluation.

OBJECTIVES: The aim of this study was to determine the degree of head rotation that creates the maximal anatomic separation between the right internal jugular vein and the carotid artery. DESIGN: Single-center prospective, observational cohort study. SETTING: University medical center. PARTICIPANTS: Fifty patients aged>21 years and undergoing cardiac surgery. INTERVENTIONS: An ultrasound machine equipped with a digital caliper was used to determine the relational anatomy of the internal jugular vein and the carotid artery, with patients in the Trendelenburg position at head angles of -15°, 0°,+15°,+30°,+45°,+60°,+75°, and+90°. MEASUREMENTS AND MAIN RESULTS: When examining the percentage of the internal jugular vein vertical diameter that is not overlapped by the carotid artery (vertically unencumbered), there was a difference between the head angle groups (p<0.01). Unencumbered vertical distance was different between+75° versus 0°, and+75° versus+15°. At+75°, 60.3%±5.3% of the internal jugular vein was unencumbered vertically, whereas at 0°, it was 37.2%±3.9%, and at+15° it was 40.3%±3.8%. Only 72% of the patients were able to position their head at+75°, and 54% of the subjects were able to position their head at+90°. CONCLUSION: The authors found the internal jugular vein becomes more vertically separated from the carotid artery at more extreme angles of contralateral head rotation.

Inhibition of serum and glucocorticoid regulated kinases by GSK650394 reduced infarct size in early cerebral ischemia-reperfusion with decreased BBB disruption.

Blood-brain barrier (BBB) disruption is one of the most important pathological changes following cerebral ischemia-reperfusion. We tested whether inhibition of the serum and glucocorticoid regulated kinase 1 (SGK1) would decrease BBB disruption and contribute to decreasing infarct size in the first few hours of cerebral ischemia-reperfusion within the thrombolysis therapy time window. After transient middle cerebral artery occlusion (MCAO), an SGK1 inhibitor GSK650394, or vehicle was administered into the lateral ventricle of rats. After one hour of MCAO and two hours of reperfusion, we determined BBB disruption using the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid, and also determined infarct size, phosphorylation of NDRG1, and MMP2 protein level. Ischemia-reperfusion increased (+34%, p < 0.05) and GSK650394 decreased (-25%, p < 0.05) the Ki in the ischemic-reperfused cortex. GSK650394 decreased the percentage of cortical infarct (-31%, p < 0.001). At the same time GSK650394 reduced NDRG1 phosphorylation and MMP2 protein level in the ischemic-reperfused cortex suggesting that SGK1 was inhibited by GSK650394 and that lower MMP2 could be one of the mechanisms of decreased BBB disruption. Collectively our data suggest that GSK650394 could be neuroprotective and one of the mechanisms of the neuroprotection could be decreased BBB disruption. SGK1 inhibition within the thrombolysis therapy time window might reduce cerebral ischemia-reperfusion injury.

Adhesion molecule L1 inhibition increases infarct size in cerebral ischemia-reperfusion without change in blood-brain barrier disruption.

OBJECTIVE: Neural cell adhesion molecule L1CAM (L1) is involved in neuroprotection. To investigate a possible neuroprotective effect of L1 during ischemia, we determined whether blocking L1 with an antagonistic antibody would worsen the outcome of focal cerebral ischemia-reperfusion and increase blood-brain barrier (BBB) disruption. METHODS: Transient middle cerebral artery occlusion (MCAO) was performed in anesthetized rats. Five µg of antagonistic mouse IgG monoclonal L1 antibody 324 or non-immune control mouse IgG was applied on the ischemic-reperfused cortex during one hour of MCAO and two hours of reperfusion. At two hours of reperfusion, BBB permeability, size of infarct using tetrazolium staining, number of TUNEL-labeled apoptotic cells, and immunohistochemistry for expression of PTEN and p53 were studied. RESULTS: The antagonistic L1 antibody 324 increased the percentage of cortical infarct area (+36%), but did not affect BBB permeability in the ischemic-reperfused cortex. The antagonistic L1 antibody increased number of apoptotic neurons and p53 expression, but decreased PTEN expression. CONCLUSION: Functional antagonism of L1 increases infarct size by increasing numbers of apoptotic neurons without affecting BBB permeability during the early stage of cerebral ischemia-reperfusion. Our data suggest that L1 affects primarily the brain parenchyma rather than BBB during early stages of cerebral ischemia-reperfusion and that endogenous brain L1 may be neuroprotective.

Early and intermediate outcomes for surgical management of infective endocarditis.

OBJECTIVE: The treatment of active infective endocarditis (IE) presents a clinical dilemma with uncertain outcomes. This study sets out to determine the early and intermediate outcomes of patients treated surgically for active IE at an academic medical center. METHODS: A retrospective chart review was conducted to identify patients who underwent surgical intervention for IE at our institution from July 1st, 2011 to June 30th, 2018. In-patient records were examined to determine etiology of disease, surgical intervention type, postoperative complications, length of stay (LOS), 30-day in-hospital mortality, and 1-year survival. RESULTS: Twenty-five patients underwent surgical intervention for active IE. The average age of the patients was 47 ± 14 years old and most of the patients were male (N = 15). The majority of the patients had the mitral valve replaced (N = 10), with the remaining patients having tricuspid (N = 8) and aortic (N = 7) valve replacements. The etiology varied and included intravenous drug use (IVDU), and presence of transvenous catheters. The 30-day in-hospital mortality was 4% with 1 patient death and the 1-year survival was 80%. The average LOS was 27 days ±15 and the longest LOS was 65 days. CONCLUSIONS: Surgical management of IE can be difficult and challenging however mortality can be minimized with acceptable morbidity. The most common complication was CVA. The average LOS is longer than traditional adult cardiac surgery procedures and the recurrence rate of valvular infection is not minimal especially if the underlying etiology is IVDU.

Ruptured Giant Coronary Artery Aneurysm With Coronary Artery to Pulmonary Artery Fistula Presenting as Cardiac Tamponade Diagnosed by Intraoperative Transesophageal Echocardiography: A Case Report.

A 63-year-old woman presented with cardiac tamponade because of a ruptured giant left anterior descending coronary artery aneurysm with a fistula to the main pulmonary artery. The diagnosis was made intraoperatively during an emergent subxiphoid pericardial window using transesophageal echocardiography and confirmed by intraoperative coronary angiography. Because of this prompt diagnosis, the patient was successfully managed with immediate surgical repair of the aneurysm and fistula.

The effect of preoperative liver dysfunction on cardiac surgery outcomes.

BACKGROUND: To determine the impact of preoperative Liver Dysfunction (LD) on outcomes after elective Coronary Artery Bypass Grafting (CABG) and Valvular surgery (VS). METHODS: The Nationwide Inpatient Sample (2002-2010) was queried to identify patients with LD who had elective CABG or VS utilizing ICD-9-CM diagnosis and procedure codes. These patients were matched with the similar patients without LD (controls) by propensity score matching. Chi-square and Wilcoxon rank sum tests were used for analysis. RESULTS: We identified 1197 patients with LD (CABG = 755; VS = 442) who were matched to 2394 controls. LD significantly increased hospital mortality after both CABG (OR = 5.19; 95%CI = 2.93-9.20) and VS (OR = 7.49; 95%CI = 3.12-17.96). Overall rates of complications after CABG with LD were greater than in non-complicated cases (OR = 1.73; 95%CI = 1.46-2.05). Among them, there was an increase in bleeding (OR = 1.81;95%CI = 1.44-2.28), respiratory (OR = 2.33;95%CI = 1.86-2.93), renal (OR = 2.79;95%CI = 2.04-3.81), and infectious (OR = 2.93;95%CI = 2.14-4.01) complications. In general, the rates of complications after VS with LD were also greater than in non-complicated cases (OR = 2.77;95%CI = 2.13-3.60), specifically for bleeding (OR = 3.07;95%CI = 2.17-4.34), respiratory (OR = 3.57;95%CI = 2.51-5.07), renal (OR = 4.40;95%CI = 2.80-6.92), and infectious (OR = 4.63;95%CI = 2.85-7.51) complications. The development of LD significantly increased mean hospital length of stay (LOS) and total hospital charges after both CABG (from7.0 ± 4.0 to 9.2 ± 9.1 days and from $100,265 ± 87,107 to $117,756 ± 99,320, respectively; P < 0.0001 for both) and VS (from 7.9 ± 5.0 to 11.4 ± 9.9 days and from $134,306 ± 114,216 to $176,620 ± 147,049, respectively; P < 0.0001 for both). CONCLUSIONS: LD worsened the outcomes after cardiac surgery. It increased rates of complications, hospital mortality, length of stay and total hospital charges after both procedures.

Increasing severity of aortic atherosclerosis in coronary artery bypass grafting patients evaluated by transesophageal echocardiography.

BACKGROUND: Atherosclerotic disease in coronary artery bypass grafting (CABG) patients is a potential contributor to complications in the perioperative periods. This study was undertaken to better define how the frequency of aortic atheromatous disease among patients coming for CABG has evolved over the last decade. METHODS: Data from elective patients coming for CABG who underwent transesophageal echocardiography (TEE) examinations following induction of anesthesia were obtained for the years 2002 and 2009. Aortas were graded according to the method of Kronzon, with the following interpretations: normal = grade I, intimal thickening = 2, atheroma of less than 5 mm = 3, atheroma of > 5 mm = 4, and any mobile atheroma = 5. The data of 124 patients who underwent comprehensive exam of the aorta by one cardiac anesthesiologist were gathered and assigned into two groups based on the year TEE was done. Student's t-test was used for statistical analysis. A P value < 0.05 was considered significant. The data were presented as mean ± SD. RESULTS: There was significant difference between group 2002 (2.05 ± 1.28) and group 2009 (2.59 ± 1.11) in atheroma grade (P = 0.013). CONCLUSIONS: Patients coming for CABG in group 2009 exhibited significantly higher grades of aortic atheroma on TEE, compared to group 2002. Understanding the risk of atheroma in the elderly CABG population may help in altering surgical approaches to lessen the risk of catastrophic stroke. Potential options needing further study include the off-pump approach and modification of cross-clamp site and technique as well as other modalities.

Lower incidence of hypo-magnesemia in surgical intensive care unit patients in 2011 versus 2001.

BACKGROUND: Hypo-magnesemia is described to occur in as many as 65% of intensive care unit (ICU) patients. Magnesium (Mg) is a cofactor in over 300 enzymatic reactions involving energy metabolism, protein, and nucleic acid synthesis. The membrane pump that creates the electrical gradient across the cell membrane is dependent on Mg, and it is important in the activity of electrically excitable tissues. Since Mg regulates the movement of calcium in smooth muscle cells, it is also important in peripheral vascular tone and blood pressure. Studies have linked hypo-magnesemia to multiple chronic diseases and to a higher mortality rate. METHODS: To explore trends within our own tertiary care surgical ICU, we sampled our patients' laboratory records in 2001 and in 2011. Hypo-magnesemia in our ICU is defined as an Mg less than 2.0 mg/dL. RESULTS: This retrospective review of all SICU patients from October to December revealed that there was a significant increase (P < 0.01) in the patients with their serum Mg level measured between 2001 (89%) and 2011 (95%). There was a significant decrease (P < 0.001) in patients with hypomagnesemia (< 2 mg/dL) between 2001 (47.5%) and 2011 (33.0%). On the other hand, there was a significant increase (P < 0.001) in patients with normal serum Mg level (> 2 mg/dL) between 2001 (52.5%) and 2011 (67.0%). CONCLUSIONS: There was not only more monitoring of Mg in 2011, but a lower incidence of hypo-Mg compared to 2001. Possible explanations include changing patterns of antibiotic and diuretic use, less amphotericin use, more frequent laboratory surveillance, and better trained ICU practitioners.

Development of a neural network model for predicting glucose levels in a surgical critical care setting.

Development of neural network models for the prediction of glucose levels in critically ill patients through the application of continuous glucose monitoring may provide enhanced patient outcomes. Here we demonstrate the utilization of a predictive model in real-time bedside monitoring. Such modeling may provide intelligent/directed therapy recommendations, guidance, and ultimately automation, in the near future as a means of providing optimal patient safety and care in the provision of insulin drips to prevent hyperglycemia and hypoglycemia.