Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial.

OBJECTIVES: To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity. DESIGN: Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898). SETTING: Eligible patients were randomized prior to surgery in a 1:1 ratio. PARTICIPANTS: Potential participants were 18 years or older undergoing planned cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more. INTERVENTIONS: Five thousand patients; those allocated to a restrictive transfusion group received a red blood cell (RBC) transfusion if the hemoglobin concentration (Hb) was less than 7.5 g/dL intraoperatively and/or postoperatively. Patients allocated to a liberal transfusion strategy received RBC transfusion if the Hb was less than 9.5 g/dL intraoperatively or postoperatively in the intensive care unit or less than 8.5 g/dL on the ward. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or new onset renal dysfunction requiring dialysis at hospital discharge or day 28, whichever comes first. The primary outcome was analyzed as a per-protocol analysis. The trial monitored adherence closely as adherence to the transfusion triggers is important in ensuring that measured outcomes reflect the transfusion strategy. CONCLUSION: By randomizing prior to surgery, the TRICS III trial captured the most acute reduction in hemoglobin during cardiopulmonary bypass.

Effect of pneumoperitoneum on renal tissue oxygenation and blood flow in a rat model.

OBJECTIVES: To determine the correlation between the renal blood flow (RBF) and tissue oxygenation (PO(2)) at varying intra-abdominal pressures (IAPs) and to compare the effects on renal blood flow from carbon dioxide-induced pneumoperitoneum. METHODS: Carbon dioxide pneumoperitoneum was established in Sprague-Dawley rats (n = 6). Licox oxygen/temperature tissue probes were laparoscopically inserted into the renal parenchyma, with the renal PO(2) and RBF recorded every 30 seconds while the IAP was gradually increased. Microprobes measuring the RBF, mean arterial pressures and serum pH were placed into the parenchyma to compare the effects of carbon dioxide pneumoperitoneum (n = 7) with that of open surgery (n = 6) and medical air pneumoperitoneum (n = 6). RESULTS: Renal PO(2) was inversely related to the IAP (P < .001). Despite the reduction in IAP, the renal PO(2) in the recovery phase was lower than at baseline (P = .045). The renal PO(2) and RBF changed in a virtually identical pattern at varying levels of IAP (P > .05). The RBF significantly declined with a pneumoperitoneal pressure of 15 and 20 mm Hg (P = .022), regardless of the gas used to create the pneumoperitoneum. A partial reversal of the RBF occurred with a decrease of the IAP. The RBF in the open surgical arm remained unchanged. Although both the serum pH and the mean arterial pressure were inversely proportional to the IAP (P < .001), the mean arterial pressure was depressed to the greatest extent in the medical air group (P = .02). CONCLUSIONS: These results have demonstrated that elevated IAP secondary to pneumoperitoneum causes significant renal hypoxia and decreased RBF. Additionally, this experiment has demonstrated the use of the Licox probes in monitoring the renal PO(2) and established a novel method for evaluating the effects of IAP on the kidney.

Impact of arterial and arteriovenous renal clamping with and without intrarenal cooling on renal oxygenation and temperature in a porcine model.

BACKGROUND: As laparoscopic partial nephrectomy increases in prominence, more needs to be understood about the combined effect of the pneumoperitoneum and renal ischemia during tumor resection. The purpose of this study is to investigate the effect of combined renal hilar clamping (arterial only versus arteriovenous) and retrograde intrarenal cooling on renal temperature and oxygenation in a porcine laparoscopic partial nephrectomy model. MATERIALS AND METHODS: Under general anesthesia, laparoscopic access with intra-abdominal pressure of 15 mm Hg to the left renal hilum was obtained. Licox tissue oxygenation and temperature probes were placed into the kidney transcutaneously; measurements were taken every 30 seconds. After establishing baseline readings, either the artery alone (n=18) or the artery and vein (n=18) were clamped for 30, 60 or 90 minutes (n=12 each). During vascular clamping, retrograde, intrarenal cooling was performed with ice cold saline infused via a percutaneously placed ureteric catheter in 18 pigs. Changes in renal pO2 and temperature were analyzed with repeated measures ANCOVA in SPSS 16. RESULTS: Retrograde cooling decreased renal parenchyma to 75.8% of baseline temperature (27.9 degrees C) within 15 minutes. There were no differences in cooling whether arterial or arteriovenous clamping was used (p=0.79). In uncooled animals, there was no significant difference in the decrease in renal pO2 during the clamp phase (p=0.18) or during the recovery phase (p=0.52). During the recovery phase, renal pO2 in uncooled animals was significantly higher than in those who received cooling (p=0.01). Animals who underwent hilar clamping for extended periods (60 and 90 min) had a slower recovery of renal pO2 to baseline than those with hilar clamping for 30 minutes (p=0.04) CONCLUSION: Retrograde intrarenal cooling can reliably cool the porcine kidney to 28 degrees C, regardless of whether arterial or arteriovenous clamping is used. Renal pO2 is not significantly different between animals that undergo artery only versus en bloc hilar clamping. Pigs that were provided with retrograde cooling had a slower return of pO2 to baseline following release of hilar clamps, possibly due to hypothermic vasospasm. Clamp durations greater than 60 minutes were also associated with slower return of renal oxygenation to baseline.

Effects of resuscitation fluid on neurologic physiology after cerebral trauma and hemorrhage.

BACKGROUND: The current standard of care for fluid resuscitation of hemorrhagic hypotensive patients involves the use of crystalloid solutions. Traumatic brain injury (TBI) is often associated with hemorrhage and hypotension, which can contribute significantly to morbidity and mortality. Guidelines for the choice of fluid resuscitation and the use of red blood cell transfusions are not yet clear in the context of brain injury. METHODS: Various fluid resuscitation strategies were evaluated in Sprague-Dawley rats using fresh blood, normal saline, hypertonic saline, and albumin fluid resuscitation protocols. Mean arterial blood pressure (MAP) and cerebral oximetry were assessed in hemorrhaged groups and the mean population spike amplitudes (PSA) from the hippocampus were examined in fluid percussion injured (FPI) animals subject to hemorrhage and fluid resuscitation. RESULTS: MAP in control animals, hemorrhage and hemorrhage + albumin treated groups was 82.4 +/- 1.5 mm Hg, 55.7 +/- 1.5 mm Hg, and 97.0 +/- 3.4 mm Hg, respectively. Arterial PaO2 was higher in albumin-treated animals relative to other fluid alternatives. Regional tissue oxygen tension (PbrO2) levels in hemorrhaged animals reached significantly higher levels in albumin treated group compared with in normal saline and hypertonic saline (p < 0.001, p = 0.034, respectively). After FPI+hemorrhage, PSA values in albumin- resuscitated animals were significantly higher than in normal saline-resuscitated animals (p = 0.012). CONCLUSIONS: The results of normal saline resuscitation, relative to other fluid alternatives, suggest that a re-evaluation of current treatment strategies in hemorrhagic hypotensive TBI patients is warranted. Albumin demonstrated the greatest beneficial effects on neurophysiology endpoints over crystalloid alternatives. These data suggests that albumin resuscitation may play an important role in the treatment of hemorrhagic hypotension and TBI.

Internal mammary lymph node (IMN) coverage by standard radiation tangent fields in patients showing IMN drainage on lymphoscintigraphy: therapeutic implications.

The purpose of this report is to evaluate the variability in coverage of the internal mammary nodal chain (IMN) by standard radiation tangential fields in those patients with medial drainage on lymphoscintigraphy. Twenty-two patients who showed lymphoscintigraphic IMN drainage underwent radiation simulation planned with computed tomography (CT). Standard tangent fields were placed and CT scans were reviewed to assess IMN inclusion and correlation with presternal fat thickness. Of the 22 patients who showed IMN drainage on lymphoscintigraphy, 10 (45%) had lateral primary lesions, 9 (41%) had medial lesions and 3 (14%) had subareolar lesions. Of these 22 women, 4 (19%) had the IMN completely within the standard tangent fields. Twelve women (55%) had only partial coverage of the IMN and the remaining 6 women (27%) had the IMN region completely outside. Presternal fat thickness greater than 10 mm was less likely associated with complete IMN coverage than fat thickness 10 mm or less, P = 0.001. Lymphoscintigram drainage to the IMN in breast cancer patients may suggest an increased risk of IMN involvement. Our data show that a majority (73%) of these patients had complete or partial incidental inclusion of the IMNs with standard tangents, which may in part explain the historically low IMN failure rate.