Opioids and premature biochemical recurrence of prostate cancer: a randomised prospective clinical trial.

BACKGROUND: Prostate cancer is one of the most prevalent neoplasms in male patients, and surgery is the main treatment. Opioids can have immune modulating effects, but their relation to cancer recurrence is unclear. We evaluated whether opioids used during prostatectomy can affect biochemical recurrence-free survival. METHODS: We randomised 146 patients with prostate cancer scheduled for prostatectomy into opioid-free anaesthesia or opioid-based anaesthesia groups. Baseline characteristics, perioperative data, and level of prostate-specific antigen every 6 months for 2 yr after surgery were recorded. Prostate-specific antigen >0.2 ng ml-1 was considered biochemical recurrence. A survival analysis compared time with biochemical recurrence between the groups, and a Cox regression was modelled to evaluate which variables affect biochemical recurrence-free survival. RESULTS: We observed 31 biochemical recurrence events: 17 in the opioid-free anaesthesia group and 14 in the opioid-based anaesthesia group. Biochemical recurrence-free survival was not statistically different between groups (P=0.54). Cox regression revealed that biochemical recurrence-free survival was shorter in cases of obesity (hazard ratio [HR] 1.63, confidence interval [CI] 0.16-3.10; p=0.03), high D'Amico risk (HR 1.58, CI 0.35-2.81; P=0.012), laparoscopic surgery (HR 1.6, CI 0.38-2.84; P=0.01), stage 3 tumour pathology (HR 1.60, CI 0.20-299) and N1 status (HR 1.34, CI 0.28-2.41), and positive surgical margins (HR 1.37, CI 0.50-2.24; P=0.002). The anaesthesia technique did not affect time to biochemical recurrence (HR -1.03, CI -2.65-0.49; P=0.18). CONCLUSIONS: Intraoperative opioid use did not modify biochemical recurrence rates and biochemical recurrence-free survival in patients with intermediate and high D'Amico risk prostate cancer undergoing radical prostatectomy. CLINICAL TRIAL REGISTRATION: NCT03212456.

S100B protein and neuron-specific enolase as predictors of postoperative cognitive dysfunction in aged dogs: a case-control study.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) may be related to brain injury. S100B protein and neuron-specific enolase (NSE) have been investigated as potential biochemical markers of neural cell injury in animals and humans. This study aimed to investigate the association between POCD, brain injury and serum concentrations of S100B and NSE after periodontal surgery in aged dogs. STUDY DESIGN: Prospective observational animal study. ANIMALS: A total of 24 male and female dogs undergoing periodontal surgery. METHODS: Dogs were separated into two groups based on age: control group, 10 dogs ≤ 8 years and aged group, 14 dogs > 8 years. Cognitive function was measured preoperatively and on the seventh postoperative day using the Canine Cognitive Dysfunction Rating scale and the Age-Related Cognitive and Affective Disorders scale. S100B protein and NSE serum concentrations were measured before and immediately after the surgery. RESULTS: POCD was not observed after surgery in the present study. Serum concentrations of S100B and NSE were increased postoperatively in the control group but not in the aged group (p = 0.04 and 0.03, respectively). Preoperative S100B serum concentrations were significantly higher in the aged group (p = 0.01). CONCLUSIONS: There was no association between POCD and high concentrations of S100B and NSE in dogs. However, increased postoperative serum concentrations of S100B and NSE were found in the control group after surgery, an effect that may indicate neural damage. CLINICAL RELEVANCE: The results suggest that anesthesia and oral surgery are associated with higher postoperative serum concentrations of S100B and NSE in dogs ≤ 8 years old, which may indicate neural damage. Serum concentrations of S100B were elevated in aged dogs before anesthesia, a finding that might be related to chronic preoperative brain damage.

Predictors and their prognostic value for no ROSC and mortality after a non-cardiac surgery intraoperative cardiac arrest: a retrospective cohort study.

Data on predictors of intraoperative cardiac arrest (ICA) outcomes are scarce in the literature. This study analysed predictors of poor outcome and their prognostic value after an ICA. Clinical and laboratory data before and 24 hours (h) after ICA were analysed as predictors for no return of spontaneous circulation (ROSC) and 24 h and 1-year mortality. Receiver operating characteristic curves for each predictor and sensitivity, specificity, positive and negative likelihood ratios, and post-test probability were calculated. A total of 167,574 anaesthetic procedures were performed, including 158 cases of ICAs. Based on the predictors for no ROSC, a threshold of 13 minutes of ICA yielded the highest area under curve (AUC) (0.867[0.80-0.93]), with a sensitivity and specificity of 78.4% [69.6-86.3%] and 89.3% [80.4-96.4%], respectively. For the 1-year mortality, the GCS without the verbal component 24 h after an ICA had the highest AUC (0.616 [0.792-0.956]), with a sensitivity of 79.3% [65.5-93.1%] and specificity of 86.1 [74.4-95.4]. ICA duration and GCS 24 h after the event had the best prognostic value for no ROSC and 1-year mortality. For 24 h mortality, no predictors had prognostic value.

Predictors of major complications after elective abdominal surgery in cancer patients.

BACKGROUND: Patients undergoing abdominal surgery for solid tumours frequently develop major postoperative complications, which negatively affect quality of life, costs of care and survival. Few studies have identified the determinants of perioperative complications in this group. METHODS: We performed a prospective observational study including all patients (age > 18) undergoing abdominal surgery for cancer at a single institution between June 2011 and August 2013. Patients undergoing emergency surgery, palliative procedures, or participating in other studies were excluded. Primary outcome was a composite of 30-day all-cause mortality and infectious, cardiovascular, respiratory, neurologic, renal and surgical complications. Univariate and multiple logistic regression analyses were performed to identify predictive factors for major perioperative adverse events. RESULTS: Of a total 308 included patients, 106 (34.4%) developed a major complication during the 30-day follow-up period. Independent predictors of postoperative major complications were: age (odds ratio [OR] 1.03 [95% CI 1.01-1.06], p = 0.012 per year), ASA (American Society of Anesthesiologists) physical status greater than or equal to 3 (OR 2.61 [95% CI 1.33-5.17], p = 0.003), a preoperative haemoglobin level lower than 12 g/dL (OR 2.13 [95% CI 1.21-4.07], p = 0.014), intraoperative use of colloids (OR 1.89, [95% CI 1.03-4.07], p = 0.047), total amount of intravenous fluids (OR 1.22 [95% CI 0.98-1.59], p = 0.106 per litre), intraoperative blood losses greater than 500 mL (2.07 [95% CI 1.00-4.31], p = 0.043), and hypotension needing vasopressor support (OR 4.68 [95% CI 1.55-27.72], p = 0.004). The model had good discrimination with the area under the ROC curve being 0.80 (95% CI 0.75-0.84, p < 0.001). CONCLUSIONS: Our findings suggest that a perioperative strategy aimed at reducing perioperative complications in cancer surgery should include treatment of preoperative anaemia and an optimal fluid strategy, avoiding fluid overload and intraoperative use of colloids.

S100B protein and neuron-specific enolase as predictors of cognitive dysfunction after coronary artery bypass graft surgery: A prospective observational study.

BACKGROUND: Postoperative cognitive dysfunction (POCD) may be related to the systemic inflammatory response and an increase in serum markers of brain injury such as S100B protein and neuron-specific enolase (NSE). OBJECTIVE: The study aims to evaluate the association between POCD and serum levels of S100B and NSE after coronary artery bypass grafting surgery (CABG). DESIGN: Prospective observational study. SETTING: Single university teaching hospital. PATIENTS: We investigated 88 patients undergoing CABG. MAIN OUTCOMES MEASURES: Cognitive function was measured preoperatively, and at the 21st and 180th postoperative days (i.e. 6 months after surgery). S100B protein and NSE serum levels were evaluated preoperatively, after induction of anaesthesia, at the end of surgery and at 6 and 24 h after surgery. RESULTS: The incidence of POCD was 26.1% at 21 days after surgery and 22.7% at 6 months after surgery. Increased serum levels of S100B protein and NSE were observed postoperatively and may indicate brain damage. CONCLUSION: Although serum levels of S100B protein and NSE are both significantly increased postoperatively, our findings indicate that serum levels of S100B protein may be more accurate than NSE in the detection of POCD after CABG. TRIAL REGISTRATION: NCT01550159.

Early fluid loading in acute respiratory distress syndrome with septic shock deteriorates lung aeration without impairing arterial oxygenation: a lung ultrasound observational study.

INTRODUCTION: The study was designed to assess the impact of fluid loading on lung aeration, oxygenation and hemodynamics in patients with septic shock and acute respiratory distress syndrome (ARDS). METHODS: During a 1-year period, a prospective observational study was performed in 32 patients with septic shock and ARDS. Cardiorespiratory parameters were measured using Swan Ganz (n = 29) or PiCCO catheters (n = 3). Lung aeration and regional pulmonary blood flows were measured using bedside transthoracic ultrasound. Measurements were performed before (T0), at the end of volume expansion (T1) and 40 minutes later (T2), consisting of 1-L of saline over 30 minutes during the first 48 h following onset of septic shock and ARDS. RESULTS: Lung ultrasound score increased by 23% at T2, from 13 at baseline to 16 (P < 0.001). Cardiac index and cardiac filling pressures increased significantly at T1 (P < 0.001) and returned to control values at T2. The increase in lung ultrasound score was statistically correlated with fluid loading-induced increase in cardiac index and was not associated with increase in pulmonary shunt or regional pulmonary blood flow. At T1, PaO2/FiO2 significantly increased (P < 0.005) from 144 (123 to 198) to 165 (128 to 226) and returned to control values at T2, whereas lung ultrasound score continued to increase. CONCLUSIONS: Early fluid loading transitorily improves hemodynamics and oxygenation and worsens lung aeration. Aeration changes can be detected at the bedside by transthoracic lung ultrasound, which may serve as a safeguard against excessive fluid loading.

Cardiac compression of lung lower lobes after coronary artery bypass graft with cardiopulmonary bypass.

BACKGROUND: Atelectasis is a major cause of hypoxemia after coronary artery bypass grafting (CABG) and is commonly ascribed to general anesthesia, high inspiratory oxygen concentration and cardiopulmonary bypass (CPB). The objective of this study was to evaluate the role of heart-induced pulmonary compression after CABG with CPB. METHODS: Seventeen patients without pre-operative cardiac failure who were scheduled for coronary artery bypass graft underwent pre- and postoperative thoracic computed tomography. The cardiac mass, the pressure exerted on the lungs by the right and left heart and the fraction of collapsed lower lobe segments below and outside of the heart limits were evaluated on a computed tomography section 1 cm above the diaphragmatic cupola. RESULTS: In the postoperative period, cardiac mass increased by 32% (117±31 g versus 155±35 g, p<0.001), leading to an increase in the pressure that was exerted on the lungs by the right (2.2±0.6 g.cm(-2) versus 3.2±1.2 g.cm(-2), p<0.05) and left heart (2.4±0.7 g.cm(-2) versus 4.2±1.8 g.cm(-2), p<0.001). The proportion of collapsed lung segments beneath the heart markedly increased [from 6.7% to 32.9% on the right side (p<0.001) and from 6.2% to 29% on the left side (p<0.001)], whereas the proportion of collapsed lung segments outside of the heart limits slightly increased [from 0.7% to 10.8% on the right side (p<0.001) and from 1.5% to 12.6% on the left side (p<0.001)]. CONCLUSION: The pressure that is exerted by the heart on the lungs increased postoperatively and contributed to the collapse of subjacent pulmonary segments.

Effects of positive end-expiratory pressure titration and recruitment maneuver on lung inflammation and hyperinflation in experimental acid aspiration-induced lung injury.

BACKGROUND: In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. METHODS: Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. RESULTS: Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. CONCLUSION: In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial.

CONTEXT: Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE: To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS: The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION: Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE: Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS: Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P = .002). CONCLUSION: Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01021631.

Potassium in hemorrhagic shock: a potential marker of tissue hypoxia.

BACKGROUND: This study was designed to evaluate serum potassium level variation in a porcine model of hemorrhagic shock (HS). METHODS: Eight pigs were studied in a controlled hemorrhage model of HS. Blood withdrawal began at a 50 mL/min to 70 mL/min rate, adjusted to reach a mean arterial pressure (MAP) level of 60 mm Hg in 10 minutes. When MAP reached 60 mm Hg, the blood withdrawal rate was adjusted to maintain a MAP decrease rate of 10 mm Hg every 2 minutes to 4 minutes. Arterial and mixed venous blood samples were collected at MAP levels of 60 mm Hg, 50 mm Hg, 40 mm Hg, 30 mm Hg, 20 mm Hg, and 10 mm Hg and analyzed for oxygen saturation, Po2, Pco2, potassium, lactate, bicarbonate, hemoglobin, pH, and standard base excess. RESULTS: Significant increase in serum potassium occurred early in all animals. The rate of rise in serum potassium and its levels accompanied the hemodynamic deterioration. Hyperkalemia (K >5 mmol/L) incidence was 12.5% at 60 mm Hg and 50 mm Hg, 62.5% at 40 mm Hg, 87.5% at 30 mm Hg, and 100% at 20 mm Hg. Strong correlations were found between potassium levels and lactate (R = 0.82), SvO2 (R = 0.87), DeltapH (R = 0.83), and DeltaPco2 (R = 0.82). CONCLUSIONS: Serum potassium increase accompanies the onset of HS. The rise in serum potassium was directly related to the hemodynamic deterioration of HS and strongly correlated with markers of tissue hypoxia.

Lung pathology in fatal novel human influenza A (H1N1) infection.

RATIONALE: There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection. OBJECTIVES: The autopsy findings of 21 Brazilian patients with confirmed S-OIV infection are presented. These patients died in the winter of the southern hemisphere 2009 pandemic, with acute respiratory failure. METHODS: Lung tissue was submitted to virologic and bacteriologic analysis with real-time reverse transcriptase polymerase chain reaction and electron microscopy. Expression of toll-like receptor (TLR)-3, IFN-gamma, tumor necrosis factor-alpha, CD8(+) T cells and granzyme B(+) cells in the lungs was investigated by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Patients were aged from 1 to 68 years (72% between 30 and 59 yr) and 12 were male. Sixteen patients had preexisting medical conditions. Diffuse alveolar damage was present in 20 individuals. In six patients, diffuse alveolar damage was associated with necrotizing bronchiolitis and in five with extensive hemorrhage. There was also a cytopathic effect in the bronchial and alveolar epithelial cells, as well as necrosis, epithelial hyperplasia, and squamous metaplasia of the large airways. There was marked expression of TLR-3 and IFN-gamma and a large number of CD8(+) T cells and granzyme B(+) cells within the lung tissue. Changes in other organs were mainly secondary to multiple organ failure. CONCLUSIONS: Autopsies have shown that the main pathological changes associated with S-OIV infection are localized to the lungs, where three distinct histological patterns can be identified. We also show evidence of ongoing pulmonary aberrant immune response. Our results reinforce the usefulness of autopsy in increasing the understanding of the novel human influenza A (H1N1) infection.

Low hematocrit levels increase intracranial pressure in an animal model of cryogenic brain injury.

BACKGROUND: Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over optimal fluid management for these patients. This study aimed to investigate the effects of acute hemodilution with hydroxyethyl starch (HES) or lactated Ringer's solution (LR) in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in dogs submitted to a cryogenic brain injury model. METHODS: Design--Prospective laboratory animal study. Setting--Research laboratory in a teaching hospital. Subjects--Thirty-five male mongrel dogs. Interventions--Animals were enrolled to five groups: control, hemodilution with LR or HES 6% to an hematocrit target of 27% or 35%. RESULTS: ICP and CPP levels were measured after cryogenic brain injury. Hemodilution promotes an increment of ICP levels, which decreases CPP when hematocrit target was estimated in 27% after hemodilution. However, no differences were observed regarding crystalloid or colloid solution used for hemodilution in ICP and CPP levels. CONCLUSIONS: Hemodilution to a low hematocrit level increases ICP and decreases CPP scores in dogs submitted to a cryogenic brain injury. These results suggest that excessive hemodilution to a hematocrit below 30% should be avoided in traumatic brain injury patients.

Comparison between intermittent and continuous measurement of cardiac output after acute normovolemic hemodilution in pigs.

Continuous cardiac output (CO) and mixed venous oxygen saturation (SvO2) determined through the pulmonary artery catheter may be helpful in monitoring hemodynamic conditions in critically ill patients. This study aimed to evaluate CO and SvO2 in a model of acute normovolemic hemodilution (ANH), analyzing the accuracy of the continuous versus intermittent method for CO and SvO2 measurement in pigs. Twenty-three pigs were enrolled to three groups: control, ANH with 6% hydroxyethyl starch (HES), or ANH with lactated Ringer's (LR) solution. After hemodilution, we showed that SvO2 was reduced in both groups, mainly in LR animals (P < 0.05). Regarding the evaluation of CO, we showed an increase in both groups submitted to ANH (P < 0.05). Through Bland-Altman analysis, we showed that the continuous CO catheter presented lower values than the intermittent method after hemodilution, mainly with HES (P < 0.001), and there was no difference in the measurement of SvO2. The ANH promoted a decrease in SvO2 and an increase in CO values, mainly in animals submitted to hemodilution with HES. The use of continuous and intermittent (laboratory) measurement of SvO2 showed clinical applicability and good agreement, an effect not reproduced by the CO measurement. New studies are needed to further investigate the agreement between the continuous and intermittent methods for the measurement of CO in adverse hemodynamic conditions such as ANH.

Heart transplantation in children: clinical outcome during the early postoperative period.

As improved understanding of transplant-related death should improve survival, we report a single center's experience with pediatric heart transplantation including potential risk factors and causes of death during the early postoperative period. This prospective longitudinal study involved 51 pediatric patients ranging in age from 12 days to 15.1 yr (median: 3 yr). The following pretransplant risk factors were evaluated: diagnosis, age at transplantation, recipient sex, weight and blood type, blood type match, donor/recipient sex match, weight ratio, ischemic time, recipient's status, requirement for mechanical ventilation or circulatory support, dialysis, or inotropic support at transplantation. We also determined the actuarial survival, clinical outcomes, and causes of death in this population. Survival was 86% during the early postoperative period (

The effects of abdominal opening on respiratory mechanics during general anesthesia in normal and morbidly obese patients: a comparative study.

Morbid obesity has a profound effect on respiratory mechanics and gas exchange. However, most studies were performed in morbidly obese patients before or after anesthesia. We tested the hypothesis that anesthesia and abdominal opening could modify the elastic and resistive properties of the respiratory system. Eleven morbidly obese and eight normal-weight patients scheduled for gastric binding and cancer treatment, respectively, under laparotomy were studied. Respiratory mechanics, partitioned into its lung and chest wall components, were investigated during surgery by means of the end-inspiratory inflation occlusion method and esophageal balloon at five time points. Static respiratory and lung compliance were markedly reduced in obese patients; on the contrary, static compliance of chest wall presented comparable values in both groups. Obese patients also presented higher resistances of the total respiratory system, lung and chest wall, as well as "additional" lung resistance. Mainly in obese patients, laparotomy provoked a significant increase in lung compliance and decrease in "additional" lung resistance 1 h after the peritoneum was opened, which returned to original values after the peritoneum had been closed (P < 0.005). In obese patients, low respiratory compliance and higher airway resistance were mainly determined by the lung component.