Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis.

Cancer, currently the leading cause of death in the population aged less than 85 years, poses a significant global disease burden and is anticipated to continue to increase in incidence in both developed and developing nations. A substantial proportion of cancers are amenable to surgery, with more than 60% of patients undergoing tumour resection. Up to 80% of patients will receive anaesthesia for diagnostic, therapeutic or palliative intervention. Alarmingly, retrospective studies have implicated surgical stress in disease progression that is predominantly characterised by metastatic disease-the primary cause of cancer-associated mortality. Our understanding of the mechanisms of surgical stress and impact of perioperative interventions is, however, far from complete. Accumulating evidence from preclinical studies suggests that adrenergic-inflammatory pathways may contribute to cancer progression. Importantly, these pathways are amenable to modulation by adapting surgical (e.g. minimally invasive surgery) and anaesthetic technique (e.g. general vs. neuraxial anaesthesia). Disturbingly, drugs used for general anaesthesia (e.g. inhalational vs. intravenous anaesthesia and potentially opioid analgesia) may also affect behaviour of tumour cells and immune cells, suggesting that choice of anaesthetic agent may also be linked to adverse long-term cancer outcomes. Critically, current clinical practice guidelines on the use of anaesthetic techniques, anaesthetic agents and perioperative adjuvants (e.g. anti-inflammatory drugs) during cancer surgery do not take into account their potential effect on cancer outcomes due to a lack of robust prospective data. To help address this gap, we provide an up-to-date review of current clinical evidence supporting or refuting the role of perioperative stress, anaesthetic techniques and anaesthetic agents in cancer progression and review pre-clinical studies that provide insights into biological mechanisms.

Neuraxial Anesthesia Reduces Lymphatic Flow: Proof-of-Concept in First In-Human Study.

Dilation of lymphatic vessels may contribute to iatrogenic dissemination of cancer cells during surgery. We sought to determine whether neuraxial anesthesia reduces regional lymphatic flow. Using nuclear lymphoscintigraphy, 5 participants receiving spinal anesthesia for brachytherapy had lower extremity lymph flow at rest compared with flow under conditions of spinal anesthesia. Six limbs were analyzed. Four limbs were excluded because of failure to demonstrate lymph flow (1 patient, 2 limbs), colloid injection error (1 limb), and undiagnosed deep vein thrombosis (1 limb). All analyzed limbs showed reduced lymph flow washout from the pedal injection site (range 62%-100%) due to neuraxial anesthesia. Lymph flow was abolished in 3 limbs. We report proof-of-concept that neuraxial anesthesia reduces lymphatic flow through a likely mechanism of sympathectomy.

Ongoing provision of individual clinician performance data improves practice behavior.

BACKGROUND: Clinical practice guidelines summarize evidence from science and attempt to translate those findings into clinical practice. Pervasive and consistent adoption of these guidelines into daily provider practice has proven slow. METHODS: Using postoperative nausea and vomiting (PONV) prophylaxis guideline compliance as our metric, we compared the effects of continuing medical education (CME) alone (I), CME with a single snapshot of provider compliance (II), and ongoing reporting of provider compliance data without further CME (III). We retrospectively analyzed guideline compliance of 23,279 anesthetics at the University of Texas M.D. Anderson Cancer Center. Compliance was defined as a patient with 1 risk factor for PONV receiving at least 1 antiemetic, 2 risk factors receiving at least 2 antiemetics, and 3 risk factors receiving at least 3 antiemetics. Drugs of the same class were counted as single antiemetic administration. Propofol-based anesthetic techniques were counted as receiving 1 antiemetic. Patients with 0 risk factors for PONV were not included. We estimated the compliance rates for each of the 4 time periods of the study adjusting for multiple observations on the same clinician. Individual performance feedback was given once at 6 months after intervention I coincident with a refresher presentation on PONV (start of intervention II) and on an ongoing quarterly basis during intervention III. RESULTS: Compliance rates were not significantly influenced with CME (intervention I) compared with baseline behavior (54.5% vs 54.4%, P = 0.9140). Significant improvement occurred during the time period when CME was paired with performance data (intervention II) compared with intervention I (59.2% vs 54.4%, P = 0.0002). Further significant improvement occurred when data alone were presented (intervention III) compared with intervention II (65.1% vs 59.2%, P < 0.0001). For patients with 3 risk factors, we saw significant improvement in compliance rates during intervention III (P = 0.0002). In post hoc analysis of overtreatment, the percentage differences between the baseline and time period III decreased as the number of risk factors increased. CONCLUSIONS: We observed the greatest improvement in guideline compliance with ongoing personal performance feedback. Provider feedback can be an effective tool to modify clinical practice but can have unanticipated consequences.

Pulmonary artery catheter deviation on chest roentgenogram after cardiac operation: a sign of tamponade.

Tamponade after cardiac operations often does not manifest the classic clinical or even echocardiographic features of tamponade and may therefore be difficult to diagnose. We present 3 patients with cardiac tamponade in the early postoperative period in whom portable chest roentgenogram revealed marked leftward pulmonary artery catheter displacement at the level of the right atrium and superior vena cava due to adjacent hematoma. Awareness of this radiographic finding may allow immediate triage to a life-saving reoperation, obviating the need for further imaging or diagnostic delay.

The effect of an anatomically classified procedure on antiemetic administration in the postanesthesia care unit.

BACKGROUND: The effect of the type of surgical procedure on postoperative nausea and vomiting (PONV) rate has been debated in the literature. Our goal in this retrospective database study was to investigate the effect the type of surgical procedure (categorized and compared anatomically) has on antiemetic therapy within 2 h of admission to the postanesthesia care unit (PACU). METHODS: We retrospectively analyzed data for oncology surgeries (n = 18,109), from our automated anesthesia information system database. We classified the types of surgical procedures anatomically into seven categories, with the integumentary musculoskeletal and the superficial surgeries chosen as the referent group. Our analysis included nine other risk factors for each patient, such as gender, smoking status, history of PONV or motion sickness, duration of anesthesia, number of prophylactic antiemetics administered, intraoperative opioids, ketorolac, epidural use, and postoperative opioids. Multivariate logistic regression was used to assess the effect of the type of surgery on antiemetic administration within the first 2 h of PACU admission, while adjusting for the other risk factors. RESULTS: Compared with integumentary musculoskeletal and superficial surgeries, patients undergoing neurological (P < 0.0001), head or neck (P < 0.0001), and abdominal (P < 0.0001) surgeries were administered PACU antiemetic significantly more often, whereas patients undergoing thoracic surgeries were administered PACU antiemetic significantly less often (P = 0.02). Breast or axilla (P = 0.74) and endoscopic (P = 0.28) procedures did not differ from the referent category. Female, nonsmoker, history of PONV or motion sickness, anesthesia duration, and intraoperative and postoperative opioid administration were significantly associated with antiemetic administration during early PACU admission. CONCLUSIONS: Using our automated anesthesia information system database, we found that the type of surgery, when categorized anatomically, was associated with an increased frequency of early PACU antiemetic administration in our population.

A possible association between aprotinin and improved survival after radical surgery for mesothelioma.

BACKGROUND: Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy, an operation that does not use cardiopulmonary bypass. In this prospective, randomized, placebo-controlled, double-blind trial, the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation. METHODS: After appropriate statistical design and institutional review board approval, eligible patients who were scheduled for extrapleural pneumonectomy were randomized to receive either aprotinin or placebo during the operation. Blood loss and survival data were obtained from electronic medical records and surgical databases. RESULTS: Of 20 patients who were enrolled, 16 patients met criteria for blood loss analysis. Four patients were excluded from the blood loss analysis: Three patients were inoperable because of tumor spread and underwent limited surgery, and 1 patient died intraoperatively because of acute, massive hemorrhage. The mean blood loss was 769 mL with aprotinin versus 1832 mL with placebo (P = .05; Wilcoxon test). All 20 patients were included in survival analyses. All 9 patients who received placebo died. In contrast, 7 of 11 patients who received aprotinin remained alive at the time of the current report. Kaplan-Meier survival curves differed significantly between the 2 groups (P = .0004). A Bayesian multivariate survival analysis of 18 patients who had complete data available on 8 prognostic variables indicated a posterior probability of .99 that aprotinin was beneficial. CONCLUSIONS: Aprotinin decreased blood loss. After accounting for covariate effects, there was a significant comparative benefit with aprotinin in postoperative survival. This finding was unexpected and could not be considered conclusive because of the small size of the current study. A confirmatory study may be warranted.

Furosemide prevents apoptosis and associated gene expression in a rat model of surgical ischemic acute renal failure.

Recently, we demonstrated that furosemide improves renal hemodynamics and attenuates ischemia/reperfusion (I/R)-associated changes in angiogenesis-related gene expression. However, the effect of furosemide on I/R-induced apoptosis is not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that furosemide attenuates I/R-induced apoptosis. Male Sprague-Dawley rats anesthetized with urethane (50 mg/kg) were randomly allocated into four groups (n = 6 each): sham operated saline infusion, sham operated with furosemide (30 microg/kg/hr) infusion, unilateral renal ischemia (1 hr) followed by six hours of reperfusion, and I/R with furosemide infusion. Apoptosis was measured in kidney samples and compared between groups using ANOVA with Bonferroni correction. Apoptosis-related gene expression was assessed using microarray analysis and validated with RT-PCR. Phosphorylation of Akt was analyzed using ELISA, and data were compared between groups using the Mann Whitney U test. Compared to the control group, I/R significantly (p < 0.001) induced apoptosis in both the cortex and medulla. Similarly, microarray analysis revealed that I/R induced (< or = two-fold increase compared to control group) 73 apoptosis-related genes. Phosphorylation of Akt was significantly (p < 0.05) downregulated after I/R. Treatment with furosemide significantly (p < 0.001) reduced I/R-induced apoptosis in both the cortex and medulla and attenuated the expression of 72 I/R-induced apoptosis-related genes. Compared to the I/R group, furosemide significantly (p < 0.01) upregulated the phosphorylation of Akt. These data suggest that a low dose furosemide infusion may attenuate I/R-induced apoptosis and associated gene transcription, and imply a possible novel molecular basis for the mechanism of action of furosemide in acute renal failure.

Long-term outcome of patients with perioperative myocardial infarction as diagnosed by troponin I after routine surgical coronary artery revascularization.

OBJECTIVE: Diagnosis of perioperative myocardial infarction (P-MI) after coronary artery bypass graft (CABG) surgery traditionally relied on a combination of electrocardiographic and enzyme assay changes. Patients with Q-wave P-MIs who survive to hospital discharge have a poorer long-term prognosis. Troponin assays are more sensitive and specific for detecting minor P-MI, with an increased incidence of P-MI being reported. This study investigated if P-MI after CABG surgery, as defined by troponin-I isozyme (cTn-I), correlated with long-term outcome. DESIGN: A prospective, observational study. SETTING: A single-institution, cardiothoracic specialty hospital. PARTICIPANTS: Seventy patients undergoing elective CABG surgery. INTERVENTIONS: Patients (n = 70) were stratified into low-risk and high-risk groups according to the absence (cTn-I <15 microg/L) or presence (cTn-I >or=15 microg/L) of P-MI after CABG surgery. Patients with (n = 24) and without (n = 46) P-MI were then followed for 3 years after CABG surgery to determine the impact of cTn-I-defined P-MI on long-term outcome. MEASUREMENTS AND MAIN RESULTS: Most patients felt that their quality of life and activity index had improved and that their symptoms of angina had lessened at 12-month follow-up. However, cardiovascular event-free survival was significantly less in patients with P-MI (p = 0.01) 3 years postoperatively. The incidence for cardiovascular events was 0.24 versus 0.65 (p = 0.049) in those patients without and with P-MI, respectively. The hazard ratio (2.9; 95% confidence interval, 1.3-9.4) for cardiovascular incidents was also significantly greater in patients with P-MI. More specifically, the incidence of arrhythmia was 2.4% versus 26.1% (p < 0.01), and the incidence of vascular events was 4.9% versus 26.1% (p = 0.02) in patients without and with P-MI, respectively. CONCLUSIONS: It was shown that P-MI as defined by cTn-I is associated with an increased long-term incidence of adverse cardiovascular events. An elevated peak cTn-I level (>or=15 microg/L) identified patients at increased risk but did not have a powerful positive predictive value for either cardiovascular (48%) or vascular (26%) complications. However, a peak cTn-I <15 microg/L was a negative predictor of adverse vascular outcome (95%). This may have implications for postoperative patient follow-up.

The comparison and validity of troponin I assay systems in diagnosing myocardial ischemic injury after surgical coronary revascularization.

OBJECTIVE: A prospective observational study was conducted to test the agreement between 2 commercially available automated cardiac troponin-I immunoassay systems (Opus Plus, Behring Diagnostics UK Ltd, Hounslow, UK; AxSYM, Abbott Laboratories, Abbott Park, IL) and to determine a normal reference range and threshold value indicative of perioperative myocardial infarction (PMI) after elective coronary artery bypass graft (CABG) surgery for the Opus Plus system. DESIGN: Prospective, observational study. Setting : Single institution, cardiothoracic specialty hospital. PARTICIPANTS: Seventy patients undergoing elective CABG surgery. INTERVENTIONS: After institutional review board approval, patients received standardized anesthetic, surgical, and myocardial preservation techniques. Serial electrocardiographs, creatine kinase-MB, troponin-I, and perioperative outcome data were collected. Correlation between the immunoassay systems was tested using 124 duplicate samples from the first 18 patients. The normal reference range and threshold value indicative of PMI were tested for the Opus Plus system using duplicate samples from all 70 patients. MEASUREMENTS AND MAIN RESULTS: Peak troponin-I concentrations (median [interquartile range]) differed significantly when measured by the Opus Plus and AxSYM immunoassay systems (5.61 [3.20-22.35] microg/L v 46.50 [14.55-70.95] microg/L, respectively; p < 0.001). There was clear proportional bias that was corrected with log transformation of the raw data. By using confidence interval and receiver operating characteristic curve analysis, the authors showed that a value > or =15 mug/L was indicative of PMI (Opus Plus system) and accordingly report a 35.7% (2.9% Q-wave) overall incidence of PMI in this study population (n = 70). CONCLUSIONS: These data highlight differences between commercially available troponin-I assay systems. The authors recommend that each institution establish a local reference range and threshold indicative of perioperative myocardial infarction for its specific patient population and assay system and provide sample methodology.

Myocardial protection using fructose-1,6-diphosphate during coronary artery bypass graft surgery: a randomized, placebo-controlled clinical trial.

UNLABELLED: In vitro and in vivo studies suggest that fructose-1,6-diphosphate (FDP), an intermediary glycolytic pathway metabolite, ameliorates ischemic tissue injury through increased high-energy phosphate levels and may therefore have cardioprotective properties in patients undergoing coronary artery bypass graft (CABG) surgery. We designed a randomized, placebo-controlled, double-blinded, sequential-cohort, dose-ranging safety study to test 5 FDP dosage regimens in patients (n = 120; 60 FDP, 60 control) undergoing CABG surgery. Of these dosage regimens, 3 produced no benefit, 1 produced improved cardiac function, and 1 required adjustment as a result of metabolic acidosis. This suggests that we achieved the intended effect of a dose-ranging study. The expected response was observed in patients treated with 250 mg/kg FDP IV before surgery and 2.5 mM FDP as a cardioplegic additive (n = 15). These patients had lower serum creatine kinase-MB levels 2, 4, and 6 h after reperfusion (P < 0.05), fewer perioperative myocardial infarctions (P < 0.05), and improved postoperative cardiac function, as evidenced by higher left ventricular stroke work index (LVSWI) 6, 12, and 16 h (P < 0.01) and cardiac index (CI) at 12 and 16 h (P < 0.05) after reperfusion. Overall efficacy of FDP was tested across all regimens that included IV FDP (n = 88; 44 FDP, 44 control) using 2 (FDP versus placebo) x 3 (dose size) factorial analyses. Area-under-curve (AUC) analysis demonstrated a significant increase in CI (AUC-16h, P = 0.013) and LVSWI (AUC-16h, P = 0.003) and reduction in CK-MB levels (AUC-16h, P < 0.05) in FDP-treated patients. The internal consistency of this dataset suggests that FDP may provide myocardial protection in CABG surgery and supports previous laboratory and clinical studies of FDP in ischemic heart disease. IMPLICATIONS: Fructose-1,6-diphosphate (FDP) may increase high-energy phosphate levels under anaerobic conditions and therefore ameliorate ischemic injury. A dose-ranging safety study for FDP was conducted in patients undergoing coronary artery surgery. Preischemic provision of FDP significantly improved cardiac function and reduced perioperative ischemic injury. These myocardial protective effects may improve patient outcome after cardiac surgery.

Venous thromboembolism in the intensive care unit.

Most ICU patients have a significant number of risk factors for VTE. The high incidence of DVT in the ICU population and the recognition of a high incidence of PE at autopsy confirm this. We have alluded to the difficulty of clinical diagnosis of VTE and the need for diagnostic investigations. We have reviewed currently available diagnostic investigations with regard to their sensitivity and specificity and their practicability in ICU patients, and have formulated recommended diagnostic algorithms (Figs. 4 and 5). The most important factor in the management of VTE is prevention. In the ICU, all patients are at high risk for VTE, and therefore, at a minimum should receive subcutaneous prophylactic heparin unless it is contraindicated. Alternative methods of prophylaxis are available, and should be considered for patients who have contraindications to heparin.

Coronary revascularization: a procedure in transition from on-pump to off-pump? The role of glucose-insulin-potassium revisited in a randomized, placebo-controlled study.

OBJECTIVE: To investigate an optimized glucose-insulin-potassium (GIK) solution regimen as an alternate myocardial protective strategy in off-pump coronary artery bypass graft (OP-CAB) surgery and as a supplement to conventional coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized, placebo-controlled. SETTING: Single institution, cardiothoracic specialty hospital. PARTICIPANTS: Forty-four patients scheduled for elective multivessel coronary artery surgery using either conventional CPB (n = 22) or OP-CAB techniques (n = 22). INTERVENTIONS: Preischemic, ischemic, and postischemic administration of GIK solution was carried out, optimally dosed to ensure nonesterified fatty acid (NEFA) suppression, and supplemented with magnesium, a glycolytic enzymatic cofactor. MEASUREMENTS AND MAIN RESULTS: GIK solution therapy reduced plasma NEFA levels (p < 0.001) in OP-CAB surgery and CPB groups but failed to affect the incidence of non-Q wave perioperative myocardial infarction, incidence of postoperative atrial fibrillation, incidence of postoperative infection, reduction in creatinine clearance, or duration of postoperative intensive care unit or hospital length of stay. After adjusting for GIK solution therapy, OP-CAB surgery resulted in significantly less ischemic injury (troponin I >15 microg/L, 19.0% v 91.3%; p = 0.0001) and reduced postoperative infections (14.3% v 43.5%; p = 0.049). CONCLUSION: GIK solution therapy achieved NEFA suppression and an insignificant trend toward reduced biochemical parameters of ischemic injury in OP-CAB surgery and CPB groups, but no major clinical benefit (perioperative myocardial infarction, intensive care unit length of stay, or hospital length of stay) was shown after elective CABG surgery in low-risk patients. Compared with CPB, OP-CAB surgery significantly reduced ischemic injury and postoperative infections.

Successful repair of intraoperative aortic dissection detected by transesophageal echocardiography.

Aortic dissection is a rare but devastating complication of cardiac surgery. Early intraoperative diagnosis and management are essential for a favorable outcome. We describe the case of a 69-year-old man with worsening dyspnea who was admitted for mitral valve replacement having previously had a mitral valve repair. Precardiopulmonary bypass transesophageal echocardiography confirmed mitral regurgitation and showed mild atherosclerotic changes in the descending aorta. Following successful replacement of the mitral valve, an attempt to wean from cardiopulmonary bypass failed. This was characterized by acute onset hypovolemia. The transesophageal echocardiography showed the presence of features of acute aortic dissection involving only the descending aorta without identifying the entry point. The tear was successfully repaired by direct suture within the lumen.