A novel two-stage approach to the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome.

OBJECTIVE: To present the early results of a new technique for the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome. PATIENTS AND METHODS: The first stage involves transdiaphragmatic debulking of the right heart, inferior vena cava (IVC) and hepatic veins via median sternotomy, followed by a purse-string suture placed in the IVC below the hepatic veins. The second stage is performed separately and involves en bloc resection of the affected kidney, and IVC and vascular reconstruction via an abdominal incision. RESULTS: Three of five patients presented with clinical Budd-Chiari syndrome; two had radiological features only. The median time between surgical procedures was 12 days (IQR 13 days). Four of the five patients had a R0 resection. While all five patients successfully completed both operative stages, one patient died 22 days after the second stage. Of the remaining four, all survive with no disease recurrence. CONCLUSION: While we continue to compile longer-term data for a larger follow-up series, these preliminary findings show the feasibility of this technique and support the development of this programme of surgery.

Associations Between Nonanemic Iron Deficiency and Postoperative Outcomes in Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Preoperative screening for iron deficiency is a part of patient blood management protocols. This systematic review, meta-analysis, and meta-regression reviews the association between nonanemic iron deficiency and postoperative outcomes in patients undergoing cardiac surgery. We aimed to determine whether preoperative screening for nonanemic iron deficiency should be recommended in patients undergoing cardiac surgery. METHODS: Electronic databases MEDLINE (Ovid), Embase (Ovid), and Scopus were searched from inception until December 9, 2022. Studies were considered for inclusion if they (1) used an observational study design; (2) enrolled adult patients undergoing cardiac surgery; and (3) included an iron-deficient and iron-replete group, defined using serum ferritin and/or transferrin saturation. The primary outcome was the length of acute hospital stay. Secondary outcomes included length of intensive care unit stay, requirement for allogeneic red blood cell transfusion, number of red blood cell units transfused, days alive and at home at postoperative days 30 and 90, all-cause postoperative complications, postoperative infection, mortality, and hospital readmission. Meta-regression was performed to assess the effects of study and patient-level factors on the associations between nonanemic iron deficiency and specific outcomes. Individual study quality was assessed using the Risk of Bias in Non-Randomized Studies of Exposures (ROBINS-E) tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to determine the quality of evidence for each outcome. RESULTS: Eight studies (2683 patients) were included. No significant association was observed between nonanemic iron deficiency and any of the primary or secondary outcomes except for an increased requirement for allogeneic red blood cell transfusion (odds ratio [OR], 1.39 [95% confidence interval, CI, 1.16-1.68; P < .001; I2 2.8%]). Meta-regression did not identify any potential sources of heterogeneity to explain variation in individual study results. The quality of evidence was rated as "low" or "very low" for all outcomes. CONCLUSIONS: Few high-quality studies are available to assess associations between nonanemic iron deficiency and outcomes after cardiac surgery. Acknowledging these limitations, the presence of preoperative nonanemic iron deficiency was not associated with a change in the primary outcome of length of hospital stay, or any patient-centered secondary outcome compared to those without iron deficiency. There was an association with increased requirement for allogeneic red blood cell transfusion, but this did not impact the reported patient-centered outcomes.

Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2 ), and, in some protocols, brain tissue PO2 , by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2 , rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg-1 min-1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO2 , but increased renal cortical and medullary PO2 . Increasing blood haemoglobin concentration increased rSO2 , but not renal PO2 . We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.

Associations between postoperative anaemia and unplanned readmission to hospital after major surgery: a retrospective cohort study†.

BACKGROUND: Anaemia following major surgery may be associated with unplanned readmission to hospital. However, the severity-response relationship between the degree of anaemia at discharge and the risk of unplanned readmission is poorly defined. We aimed to describe the severity-response relationship between haemoglobin concentration at the time of discharge and the risk of unplanned readmission in a cohort of patients undergoing different types of major surgery. METHODS: We performed a retrospective cohort study in a single tertiary health service, including all patients who underwent major surgery (orthopaedic, abdominal, cardiac or thoracic) between 1 May 2011 and 1 February 2022. The primary outcome was unplanned readmission to hospital in the 90 days following discharge after the index surgical procedure. These complex, non-linear relationships were modelled with restricted cubic splines. RESULTS: We identified 22,134 patients and included 14,635 in the primary analysis, of whom 1804 (12%) experienced at least one unplanned readmission. The odds of unplanned readmission rose when the discharge haemoglobin concentration was < 100 g.l-1 (p < 0.001). On subgroup analysis, the haemoglobin threshold below which odds of readmission began to increase appeared to be higher in patients undergoing emergency surgery (110 g.l-1; p < 0.001) compared with elective surgery. Declining discharge haemoglobin concentration was associated with increased odds ratios (95%CI) of unplanned readmission in patients undergoing orthopaedic (1.08 (1.01-1.15), p = 0.03), abdominal (1.13 (1.07-1.19), p < 0.001) and thoracic (1.12 (1.01-1.24), p = 0.03) procedures, but not cardiac surgery (1.09 (0.99-1.19), p = 0.07). CONCLUSIONS: Our findings suggest that a haemoglobin concentration < 100 g.l-1 following elective procedures and < 110 g.l-1 following emergency procedures, at the time of hospital discharge after major surgery, was associated with unplanned readmission. Future interventional trials that aim to treat postoperative anaemia and reduce unplanned readmission should include patients with discharge haemoglobin below these thresholds.

Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial.

BACKGROUND: The role of the renin-angiotensin-aldosterone axis in vasoplegia after cardiac surgery remains unclear. We tested the hypothesis that, compared with norepinephrine, infusion of angiotensin II titrated to achieve similar mean arterial pressure (MAP) would suppress plasma renin concentration (PRC) while maintaining aldosterone levels. METHODS: In a double-blind, randomised controlled trial, subjects received either an infusion of angiotensin II or norepinephrine to maintain MAP 70-80 mm Hg from induction of anaesthesia. We compared PRC, aldosterone, dipeptidyl peptidase-3, and angiotensin-converting enzyme 2 activity between treatment groups, before surgery, on ICU admission, and 24 h after surgery. RESULTS: In 60 patients (11.7% female; mean age 68 yr [11 yr]), norepinephrine increased median PRC at ICU admission (median difference [MD] 46 [inter-quartile range, IQR, 3-88] µU ml-1; P<0.001) but angiotensin II did not (MD -3 [IQR -62 to 35] µU ml-1; P=0.36). Aldosterone levels increased with both. The aldosterone:PRC ratio did not change with norepinephrine (MD -0.01 [IQR -0.14 to 0.03] µU ml-1 per ng dl-1, P=0.76) but increased with angiotensin II (MD 0.05 [IQR 0.004-0.26] µU ml-1 per ng dl-1, P<0.001). The upper quartile of PRC before surgery was associated with higher vasopressor requirements when norepinephrine was used to maintain MAP, but not angiotensin II. Dipeptidyl peptidase-3 levels and angiotensin-converting enzyme 2 activities were similar at all time points. CONCLUSIONS: Angiotensin II suppressed renin release while maintaining aldosterone levels compared with norepinephrine. Higher plasma renin concentration before surgery was associated with greater vasopressor requirement for norepinephrine, but not angiotensin II. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry-ACTRN12621000195853 23/02/2021.

A protocol for a prospective, multicentre observational study to determine if nonanaemic iron deficiency worsens postoperative outcome in patients undergoing elective surgery for resection of colorectal cancer: The NATO study.

BACKGROUND: Preoperative absolute and functional iron deficiency anaemia is associated with poor postoperative outcomes in patients undergoing surgery for colorectal cancer. It is biologically plausible that "early", or "nonanaemic" iron deficiency may also be associated with worse postoperative outcomes in similar cohorts, albeit at lesser severity than that seen for anaemia. The evidence supporting this assertion is of low quality. METHODS: We have designed a prospective, observational study to delineate associations between preoperative non-anaemic iron deficiency and postoperative outcomes after surgery for colorectal cancer. Patients without anaemia, undergoing elective surgery for colorectal cancer will be allocated to an iron replete or an iron deficient group based on preoperative transferrin saturation. The primary outcome is days alive and at home on postoperative day 90. Secondary outcomes include days alive and at home on postoperative day 30, length of hospital stay, readmission to acute care, postoperative complications, health-related quality of life scores, quality of postoperative recovery, and requirement for allogeneic blood transfusion. The planned sample size is 422 patients, which has 80% power to detect a two-day difference in the primary outcome. The study commenced in May 2019. CONCLUSION: The results of this study will provide patients and clinicians with high-quality evidence concerning associations between nonanaemic iron deficiency and patient-centred outcomes after surgery for colorectal cancer. The study will be conducted in multiple urban and rural centres across Australia and New Zealand. The results will be highly generalisable to contemporary surgical practice and should be rapidly translated.

Associations Between Systemic and Cerebral Inflammation in an Ovine Model of Cardiopulmonary Bypass.

BACKGROUND: Intraoperative inflammation may contribute to postoperative neurocognitive disorders after cardiac surgery requiring cardiopulmonary bypass (CPB). However, the relative contributions of general anesthesia (GA), surgical site injury, and CPB are unclear. METHODS: In adult female sheep, we investigated (1) the temporal profile of proinflammatory and anti-inflammatory cytokines and (2) the extent of microglia activation across major cerebral cortical regions during GA and surgical trauma with and without CPB (N = 5/group). Sheep were studied while conscious, during GA and surgical trauma, with and without CPB. RESULTS: Plasma tumor necrosis factor-alpha (mean [95% confidence intervals], 3.7 [2.5-4.9] vs 1.6 [0.8-2.3] ng/mL; P = .0004) and interleukin-6 levels (4.4 [3.0-5.8] vs 1.6 [0.8-2.3] ng/mL; P = .029) were significantly higher at 1.5 hours, with a further increase in interleukin-6 at 3 hours (7.0 [3.7-10.3] vs 1.8 [1.1-2.6] ng/mL; P < .0001) in animals undergoing CPB compared with those that did not. Although cerebral oxygen saturation was preserved throughout CPB, there was pronounced neuroinflammation as characterized by greater microglia circularity within the frontal cortex of sheep that underwent CPB compared with those that did not (0.34 [0.32-0.37] vs 0.30 [0.29-0.32]; P = .029). Moreover, microglia had fewer branches within the parietal (7.7 [6.5-8.9] vs 10.9 [9.4-12.5]; P = .001) and temporal (7.8 [7.2-8.3] vs 9.9 [8.2-11.7]; P = .020) cortices in sheep that underwent CPB compared with those that did not. CONCLUSIONS: CPB enhanced the release of proinflammatory cytokines beyond that initiated by GA and surgical trauma. This systemic inflammation was associated with microglial activation across 3 major cerebral cortical regions, with a phagocytic microglia phenotype within the frontal cortex, and an inflammatory microglia phenotype within the parietal and temporal cortices. These data provide direct histopathological evidence of CPB-induced neuroinflammation in a large animal model and provide further mechanistic data on how CPB-induced cerebral inflammation might drive postoperative neurocognitive disorders in humans.

Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial.

BACKGROUND: The dose of protamine required following cardiopulmonary bypass (CPB) is often determined by the dose of heparin required pre-CPB, expressed as a fixed ratio. Dosing based on mathematical models of heparin clearance is postulated to improve protamine dosing precision and coagulation. We hypothesised that protamine dosing based on a 2-compartment model would improve thromboelastography (TEG) parameters and reduce the dose of protamine administered, relative to a fixed ratio. METHODS AND FINDINGS: We undertook a 2-stage, adaptive randomised controlled trial, allocating 228 participants to receive protamine dosed according to a mathematical model of heparin clearance or a fixed ratio of 1 mg of protamine for every 100 IU of heparin required to establish anticoagulation pre-CPB. A planned, blinded interim analysis was undertaken after the recruitment of 50% of the study cohort. Following this, the randomisation ratio was adapted from 1:1 to 1:1.33 to increase recruitment to the superior arm while maintaining study power. At the conclusion of trial recruitment, we had randomised 121 patients to the intervention arm and 107 patients to the control arm. The primary endpoint was kaolin TEG r-time measured 3 minutes after protamine administration at the end of CPB. Secondary endpoints included ratio of kaolin TEG r-time pre-CPB to the same metric following protamine administration, requirement for allogeneic red cell transfusion, intercostal catheter drainage at 4 hours postoperatively, and the requirement for reoperation due to bleeding. The trial was listed on a clinical trial registry (ClinicalTrials.gov Identifier: NCT03532594). Participants were recruited between April 2018 and August 2019. Those in the intervention/model group had a shorter mean kaolin r-time (6.58 [SD 2.50] vs. 8.08 [SD 3.98] minutes; p = 0.0016) post-CPB. The post-protamine thromboelastogram of the model group was closer to pre-CPB parameters (median pre-CPB to post-protamine kaolin r-time ratio 0.96 [IQR 0.78-1.14] vs. 0.75 [IQR 0.57-0.99]; p < 0.001). We found no evidence of a difference in median mediastinal/pleural drainage at 4 hours postoperatively (140 [IQR 75-245] vs. 135 [IQR 94-222] mL; p = 0.85) or requirement (as a binary outcome) for packed red blood cell transfusion at 24 hours postoperatively (19 [15.8%] vs. 14 [13.1%] p = 0.69). Those in the model group had a lower median protamine dose (180 [IQR 160-210] vs. 280 [IQR 250-300] mg; p < 0.001). Important limitations of this study include an unblinded design and lack of generalisability to certain populations deliberately excluded from the study (specifically children, patients with a total body weight >120 kg, and patients requiring therapeutic hypothermia to <28°C). CONCLUSIONS: Using a mathematical model to guide protamine dosing in patients following CPB improved TEG r-time and reduced the dose administered relative to a fixed ratio. No differences were detected in postoperative mediastinal/pleural drainage or red blood cell transfusion requirement in our cohort of low-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov Unique identifier NCT03532594.

30-Day Outcomes Post Veno-Arterial Extra Corporeal Membrane Oxygenation (VA-ECMO) After Cardiac Surgery and Predictors of Survival.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is sometimes needed for post-cardiotomy cardiogenic shock (PCCS). There is little data regarding outcomes in the Australian context, particularly in a non-cardiac transplant centre. Our aim was to report on 30-day outcomes after patients with PCCS treated with VA-ECMO in an Australian non-cardiac transplant tertiary centre, and to determine risk factors for non-survival in this population. METHODS: A retrospective analysis was performed on all adults treated with VA-ECMO for PCCS between August 2001 and September 2016 at our centre. Univariate analysis with adjustment for multiplicity identified risk factors for non-survival. Area under the receiver operating characteristics (AUROC) method was used to assess their predictive value. RESULTS: We identified 64 patients out of 5,502 open-heart surgery cases of which three patients did not meet inclusion criteria. Mean (SD) age was 63 (14) years. Survival to hospital discharge or 30 days post VA-ECMO occurred in 27/61 (44%) patients. VA-ECMO was able to be weaned in 44/61 patients (72%); 54/61 patients (89%) had at least one major complication. Prior to VA-ECMO initiation, no statistically significant differences between survivors and non-survivors could be determined. After VA-ECMO initiation, only 24-hour nadir lactate and 48-hour nadir lactate levels were significantly different between survivors and non-survivors (1.50 mmol/L vs 3.20 mmol/L p=0.001; and 1.20 mmol/L vs. 1.90 mmol/L p=0.001 respectively). For mortality prediction, 24- and 48-hour nadir lactate levels had AUROCs of 0.775 and 0.782, respectively. CONCLUSIONS: VA-ECMO is associated with acceptable survival rates but significant morbidity. Nadir lactate levels in the first 24 and 48 hours after VA-ECMO initiation may be useful in predicting early survival.

Intravenous iron therapy for non-anaemic, iron-deficient adults.

BACKGROUND: Iron deficiency is one of the most common nutritional deficiencies, and has a number of physiological manifestations. Early, or non-anaemic iron deficiency can result in fatigue and diminished exercise capacity. Oral iron preparations have a high incidence of intolerable side effects, and are ineffective in certain forms of iron deficiency. Consequently, intravenous iron preparations are increasingly used in the treatment of non-anaemic iron deficiency. The newer, more stable iron preparations in particular purport to have a lower incidence of side effects, and are now used across a range of different patient populations. OBJECTIVES: To assess the effects of intravenous iron therapy in the treatment of adults with non-anaemic iron deficiency. SEARCH METHODS: On 18 October 2019 we electronically searched CENTRAL, MEDLINE, Embase, two further databases and two trials registries 2019. We handsearched the references of full-text extracted studies, and contacted relevant study authors for additional data. SELECTION CRITERIA: We included randomised controlled trials that compared any intravenous iron preparation to placebo in adults. We excluded other forms of comparison such as oral iron versus placebo, intramuscular iron versus placebo, or intravenous iron studies where other iron preparations were used as the comparator. We also excluded studies involving erythropoietin therapy or obstetric populations. DATA COLLECTION AND ANALYSIS: Two review authors screened references for eligibility, extracted data and assessed risk of bias. We resolved differences in opinion through discussion and consensus, and where necessary, involved a third review author to adjudicate disputes. We contacted study authors to request additional data where appropriate. The primary outcome measures were haemoglobin concentration at the end of follow-up, and quality-of-life scores at end of follow-up. Secondary outcome measures were serum ferritin, peak oxygen consumption (as measured by cardiopulmonary exercise testing), adverse effects (graded as mild to moderate and severe) and bacterial infection. We pooled data for continuous outcomes, which we then reported as mean differences (MDs) with 95% confidence intervals (CIs). We reported quality-of-life metrics as standardised mean difference (SMD), and then converted them back into a more familiar measure, the Piper Fatigue Scale. We analysed dichotomous outcomes as risk ratios (RRs). Given an expected degree of heterogeneity, we used a random-effects model for all outcomes. We performed the analysis with the software package Review Manager 5. MAIN RESULTS: This review includes 11 studies with 1074 participants. Outcome metrics for which data were available (haemoglobin concentration, quality-of-life scores, serum ferritin, peak oxygen consumption and mild to moderate adverse effects) were similar across the included studies. The incidence of severe adverse events across all studies was zero. None of the studies measured bacterial infection as a specific outcome metric. Substantial heterogeneity influenced the results of the meta-analysis, arising from differing patient populations, definitions of iron deficiency, iron preparations and dosing regimens, and time to end of follow-up. Consequently, many outcomes are reported with small group sizes and wide confidence intervals, with a subsequent downgrading in the quality of evidence. The level of bias in many included studies was high, further reducing confidence in the robustness of the results. We found that intravenous iron therapy may lead to a small increase in haemoglobin concentration of limited clinical significance compared to placebo (MD 3.04 g/L, 95% CI 0.65 to 5.42; I2 = 42%; 8 studies, 548 participants; low-quality evidence). Quality-of-life scores (Piper Fatigue Scale MD 0.73, 95% CI 0.29 to 1.18; I2 = 0%; studies = 3) and peak oxygen consumption (MD 2.77 mL/kg/min, 95% CI -0.89 to 6.43; I2 = 36%; 2 studies, 32 participants) were associated with very low-quality evidence, and we remain uncertain about the role of intravenous iron for these metrics. We were unable to present pooled estimates for the outcomes of serum ferritin at the end of follow-up or mild to moderate adverse effects due to extreme statistical heterogeneity. Ultimately, despite the results of the meta-analysis, the low- or very low-quality evidence for all outcomes precludes any meaningful interpretation of results beyond suggesting that further research is needed. We performed a Trial Sequential Analysis for all major outcomes, none of which could be said to have reached a necessary effect size. AUTHORS' CONCLUSIONS: Current evidence is insufficient to show benefit of intravenous iron preparations for the treatment of non-anaemic iron deficiency across a variety of patient populations, beyond stating that it may result in a small, clinically insignificant increase in haemoglobin concentration. However, the certainty for even this outcome remains limited. Robust data for the effectiveness of intravenous iron for non-anaemic iron deficiency is still lacking, and larger studies are required to assess the effect of this therapy on laboratory, patient-centric, and adverse-effect outcomes.

Global Cardioplegia Practices: Results from the Global Cardiopulmonary Bypass Survey.

Despite the ubiquitous use of cardioplegia in cardiac surgery, there is a lack of agreement on various aspects of cardioplegia practice. To discover current cardioplegia practices throughout the world, we undertook a global survey to document contemporary cardiopulmonary bypass practices. A 16-question, Internet-based survey was distributed by regional specialist societies, targeting adult cardiac anesthesiologists. Ten questions concerned caseload and cardioplegia practices, the remaining questions examined anticoagulation and pump-priming practices. The survey was available in English, Spanish, and Portuguese. The survey was launched in June 2015 and remained open until May 2016. A total of 923 responses were analyzed, summarizing practice in Europe (269), North America (334), South America (215), and Australia/New Zealand (105). Inter-regional responses differed for all questions asked (p < .001). In all regions other than South America, blood cardioplegia was the common arrest technique used. The most commonly used cardioplegia solutions were: St. Thomas, Bretschneider, and University of Wisconsin with significant regional variation. The use of additives (most commonly glucose, glutamate, tris-hydroxymethyl aminomethane, and aspartate) varied significantly. This survey has revealed significant variation in international practice with regards to myocardial protection, and is a reminder that there is no clear consensus on the use of cardioplegia. It is unclear why regional practice groups made the choices they have and the clinical impact remains unclear.

The effect of protamine dosing variation on bleeding and transfusion after heparinisation for cardiopulmonary bypass.

INTRODUCTION: Accurate dosing of protamine reversal following on-pump cardiac surgical procedures is challenging, with both excessive and inadequate administration recognised to increase bleeding risk. We aimed to examine the relationship between three ratios for heparin reversal and markers of haemostasis. METHODS: A retrospective analysis of a prospectively collected database was undertaken at a single tertiary cardiac unit, reviewing all cases of on-pump coronary artery bypass grafts and single valve replacements from 01/01/2011 to 31/12/2015. The ratio between total intra-operative heparin and protamine was stratified to three groups (low: ≤0.6 mg per 100 IU of heparin, moderate: 0.6-1.0 and high: >1.0) and related to the primary outcome of red blood cell (RBC) transfusion, with secondary outcomes being the number of units transfused, the haemoglobin differential and mediastinal drain output at 4 hours. RESULTS: Of the 803 patients identified, 338 received a blood transfusion, with 1035 units being used. Eighteen percent of individuals (145) received a low ratio, 50% (404) received a moderate ratio and 32% (254) a high ratio. Using the moderate group as a reference, the low dose group was 56.5% less likely to have received a RBC transfusion (OR 0.435; 95% CI 0.270:0.703 p=0.001) while the high dose group carried a 241% increased association with transfusion (OR 3.412; 95% CI 2.399:4.853 p<0.001). For those transfused, a lower protamine:heparin ratio was associated with a lower number of units transfused, lesser haemoglobin differential and less mediastinal drain output. CONCLUSION: Higher doses of intra-operative protamine relative to heparin are associated with greater risk of transfusion and post-operative bleeding.

Pump Priming Practices and Anticoagulation in Cardiac Surgery: Results From the Global Cardiopulmonary Bypass Survey.

BACKGROUND: Regional patterns of practice in cardiopulmonary bypass remain poorly understood with conflicting evidence regarding the best choices in pump priming preferences with respect to colloid and crystalloid and different types of fluid within these categories. In light of the variation in the literature, we hypothesized there would be considerable regional differences in cardiopulmonary bypass practice, particularly with respect to the type of fluid used to prime the extracorporeal circuit. METHODS: A 16-question, Internet-based survey was distributed by various regional specialist societies, targeting adult cardiac anesthesiologists. One question was directly relevant to activated clotting time and 5 concerned pump priming choices with respect to crystalloid and colloid types and additives. The remaining questions concerned cardioplegia choices. The survey remained open from June 2015 to May 2016. RESULTS: A total of 923 responses were analyzed. Estimated response rates from Europe, North America, Australia/New Zealand, and South America were 19.77%, 8.06%, 16.30%, and 1.68%, respectively. The majority of respondents worldwide considered an activated clotting time of <400 seconds as unsafe for bypass (92.5%). Crystalloid as a sole fluid type remains the most common priming solution worldwide (38.1%) although combinations with colloid (23.8%) were also popular. Retrograde autologous priming was used by 17.9% of respondents. Heparin was the most frequently used prime additive (43.0%) followed by mannitol (35.2%). Variation was demonstrated within some of these categories reflective of differences in regional practices. CONCLUSIONS: Differences exist in some specific areas between regional cardiopulmonary bypass techniques with respect to pump priming and anticoagulation practices. The significance of these differences with respect to patient outcome is uncertain and requires further study.

Intubated Versus Nonintubated General Anesthesia for Video-Assisted Thoracoscopic Surgery-A Case-Control Study.

OBJECTIVE: General anesthesia with endobronchial intubation and one-lung positive-pressure ventilation always has been considered mandatory for thoracic surgery. Recently, there has been interest in nonintubated techniques for video-assisted thoracoscopic surgery (VATS) in awake and sedated patients. The authors' center developed a nonintubated technique with spontaneous ventilation with the patient under general anesthesia using a supraglottic airway device. The authors believe that this was the first study to compare a nonintubated general anesthetic technique with an intubated general anesthetic technique for VATS. DESIGN: Retrospective, observational study. SETTING: Specialist cardiothoracic hospital in the United Kingdom. PARTICIPANTS: All patients who underwent elective minor VATS over 8 months (n = 73). INTERVENTIONS: A nonintubated general anesthetic technique with spontaneous ventilation via a supraglottic airway device was used for minor VATS procedures. This was compared with a case-matched intubated group. MEASUREMENTS AND MAIN RESULTS: Both groups had comparable baseline characteristics and surgical procedures. The anesthetic time was shorter in the nonintubated group (13.6±8.3 v 24.1±10.9 minutes, p<0.001). Surgical operating time and feasibility were similar. Intraoperatively, there were increases in end-tidal carbon dioxide (59.1±12.9 v 41.8±4.6, p<0.001) and respiratory rate (17.8±5.6 v 13.5±2.0, p<0.001) in the nonintubated group. Fewer patients in the nonintubated group had moderate-severe pain during recovery (19.4% v 48.4%, p = 0.02) and pain on discharge to the ward (25.8% v 61.3%, p = 0.004). There was a trend toward shorter recovery times, reduced oxygen requirement, and shorter hospital stays in the nonintubated group. CONCLUSIONS: A nonintubated general anesthetic technique is a feasible alternative to intubated general anesthesia for minor VATS procedures.

Pilot validation of an individualised pharmacokinetic algorithm for protamine dosing after systemic heparinisation for cardiopulmonary bypass.

INTRODUCTION: This manuscript represents a pilot study assessing the feasibility of a single-compartment, individualised, pharmacokinetic algorithm for protamine dosing after cardiopulmonary bypass. METHODS: A pilot cohort study in a specialist NHS cardiothoracic hospital targeting patients undergoing elective cardiac surgery using cardiopulmonary bypass. Patients received protamine doses according to a pharmacokinetic algorithm (n = 30) or using an empirical, fixed-dose model (n = 30). Categorical differences between the groups were evaluated using the Chi-squared test or Fisher's exact test. Continuous data was analysed using a paired Student's t-test for parametric data and the paired samples Wilcoxon test for non-parametric data. RESULTS: Patients who had protamine dosing according to the algorithm demonstrated a lower protamine requirement post-bypass relative to empirical management as measured by absolute dose (243 ± 49mg vs. 305 ± 34.7mg; p<0.001) and the heparin to protamine ratio (0.79 ± 0.12 vs. 1.1 ± 0.15; p<0.001). There was no difference in the pre- to post-bypass activated clotting time (ACT) ratio (1.05 ± 0.12 vs. 1.02 ± 0.15; p=0.9). Patients who received protamine according to the algorithm had no significant difference in transfusion requirement (13.3% vs. 30.0%; p=0.21). CONCLUSIONS: This study showed that an individualized pharmacokinetic algorithm for the reversal of heparin after cardiopulmonary bypass is feasible in comparison with a fixed dosing strategy and may reduce the protamine requirement following on-pump cardiac surgery.