Impact of the COVID-19 Pandemic on the Outcomes of Patients Undergoing Oncological Surgeries: CORONAL Study.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on postoperative recovery from oncology surgeries should be understood for the clinical decision-making. Therefore, this study was designed to evaluate the postoperative cumulative 28-day mortality and the morbidity of surgical oncology patients during the COVID-19 pandemic. METHODS: This retrospective cohort study included patients consecutively admitted to intensive care units (ICU) of three centres for postoperative care of oncologic surgeries between March to June 2019 (first phase) and March to June 2020 (second phase). The primary outcome was cumulative 28-day postoperative mortality. Secondary outcomes were postoperative organic dysfunction and the incidence of clinical complications. Because of the possibility of imbalance between groups, adjusted analyses were performed: Cox proportional hazards model (primary outcome) and multiple logistic regression model (secondary outcomes). RESULTS: After screening 328 patients, 291 were included. The proportional hazard of cumulative 28-day mortality was higher in the second phase than that in the first phase in the Cox model, with the adjusted hazard ratio of 4.35 (95% confidence interval [CI] 2.15-8.82). The adjusted incidences of respiratory complications (odds ratio [OR] 5.35; 95% CI 1.42-20.11) and pulmonary infections (OR 1.53; 95% CI 1.08-2.17) were higher in the second phase. However, the adjusted incidence of other infections was lower in the second phase (OR 0.78; 95% CI 0.67-0.91). CONCLUSIONS: Surgical oncology patients who underwent postoperative care in the intensive care unit during the COVID-19 pandemic had higher hazard of 28-day mortality. Furthermore, these patients had higher odds of respiratory complications and pulmonary infections. Trials registration The study is registered in the Brazilian Registry of Clinical Trials under the code RBR-8ygjpqm, UTN code U1111-1293-5414.

Predicting short-term outcomes in brain-injured patients: a comprehensive approach with transcranial Doppler and intracranial compliance assessment.

Neurocritical patients frequently exhibit abnormalities in cerebral hemodynamics (CH) and/or intracranial compliance (ICC), all of which significantly impact their clinical outcomes. Transcranial Doppler (TCD) and the cranial micro-deformation sensor (B4C) are valuable techniques for assessing CH and ICC, respectively. However, there is a scarcity of data regarding the predictive value of these techniques in determining patient outcomes. We prospectively included neurocritical patients undergoing intracranial pressure (ICP) monitoring within the first 5 days of hospital admission for TCD and B4C assessments. Comprehensive clinical data were collected alongside parameters obtained from TCD (including the estimated ICP [eICP] and estimated cerebral perfusion pressure [eCPP]) and B4C (measured as the P2/P1 ratio). These parameters were evaluated individually as well as in combination. The short-term outcomes (STO) of interest were the therapy intensity levels (TIL) for ICP management recommended by the Seattle International Brain Injury Consensus Conference, as TIL 0 (STO 1), TIL 1-3 (STO 2) and death (STO 3), at the seventh day after last data collection. The dataset was randomly separated in test and training samples, area under the curve (AUC) was used to represent the noninvasive techniques ability on the STO prediction and association with ICP. A total of 98 patients were included, with 67% having experienced severe traumatic brain injury and 15% subarachnoid hemorrhage, whilst the remaining patients had ischemic or hemorrhagic stroke. ICP, P2/P1, and eCPP demonstrated the highest ability to predict early mortality (p = 0.02, p = 0.02, and p = 0.006, respectively). P2/P1 was the only parameter significant for the prediction of STO 1 (p = 0.03). Combining B4C and TCD parameters, the highest AUC was 0.85 to predict death (STO 3), using P2/P1 + eCPP, whereas AUC was 0.72 to identify ICP > 20 mmHg using P2/P1 + eICP. The combined noninvasive neuromonitoring approach using eCPP and P2/P1 ratio demonstrated improved performance in predicting outcomes during the early phase after acute brain injury. The correlation with intracranial hypertension was moderate, by means of eICP and P2/P1 ratio. These results support the need for interpretation of this information in the ICU and warrant further investigations for the definition of therapy strategies using ancillary tests.

Can a Therapeutic Strategy for Hypotension Improve Cerebral Perfusion and Oxygenation in an Experimental Model of Hemorrhagic Shock and Severe Traumatic Brain Injury?

BACKGROUND: Restoration of brain tissue perfusion is a determining factor in the neurological evolution of patients with traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of HS without neurological damage, it was observed that the use of fluids or vasoactive drugs was effective in restoring brain perfusion; however, only terlipressin promoted restoration of cerebral oxygenation and lower expression of edema and apoptosis markers. It is unclear whether the use of vasopressor drugs is effective and beneficial during situations of TBI. The objective of this study is to compare the effects of resuscitation with saline solution and terlipressin on cerebral perfusion and oxygenation in a model of TBI and HS. METHODS: Thirty-two pigs weighing 20-30 kg were randomly allocated into four groups: control (no treatment), saline (60 ml/kg of 0.9% NaCl), terlipressin (2 mg of terlipressin), and saline plus terlipressin (20 ml/kg of 0.9% NaCl + 2 mg of terlipressin). Brain injury was induced by lateral fluid percussion, and HS was induced through pressure-controlled bleeding, aiming at a mean arterial pressure (MAP) of 40 mmHg. After 30 min of circulatory shock, resuscitation strategies were initiated according to the group. The systemic and cerebral hemodynamic and oxygenation parameters, lactate levels, and hemoglobin levels were evaluated. The data were subjected to analysis of variance for repeated measures. The significance level established for statistical analysis was p < 0.05. RESULTS: The terlipressin and saline plus terlipressin groups showed an increase in MAP that lasted until the end of the experiment (p < 0.05). There was a notable increase in intracranial pressure in all groups after starting treatment for shock. Cerebral perfusion pressure and cerebral oximetry showed no improvement after hemodynamic recovery in any group. The groups that received saline at resuscitation had the lowest hemoglobin concentrations after treatment. CONCLUSIONS: The treatment of hypotension in HS with saline and/or terlipressin cannot restore cerebral perfusion or oxygenation in experimental models of HS and severe TBI. Elevated MAP raises intracranial pressure owing to brain autoregulation dysfunction caused by TBI.

Critical Closing Pressure and Cerebrovascular Resistance Responses to Intracranial Pressure Variations in Neurocritical Patients.

BACKGROUND: Critical closing pressure (CrCP) and resistance-area product (RAP) have been conceived as compasses to optimize cerebral perfusion pressure (CPP) and monitor cerebrovascular resistance, respectively. However, for patients with acute brain injury (ABI), the impact of intracranial pressure (ICP) variability on these variables is poorly understood. The present study evaluates the effects of a controlled ICP variation on CrCP and RAP among patients with ABI. METHODS: Consecutive neurocritical patients with ICP monitoring were included along with transcranial Doppler and invasive arterial blood pressure monitoring. Internal jugular veins compression was performed for 60 s for the elevation of intracranial blood volume and ICP. Patients were separated in groups according to previous intracranial hypertension severity, with either no skull opening (Sk1), neurosurgical mass lesions evacuation, or decompressive craniectomy (DC) (patients with DC [Sk3]). RESULTS: Among 98 included patients, the correlation between change (Δ) in ICP and the corresponding ΔCrCP was strong (group Sk1 r = 0.643 [p = 0.0007], group with neurosurgical mass lesions evacuation r = 0.732 [p < 0.0001], and group Sk3 r = 0.580 [p = 0.003], respectively). Patients from group Sk3 presented a significantly higher ΔRAP (p = 0.005); however, for this group, a higher response in mean arterial pressure (change in mean arterial pressure p = 0.034) was observed. Exclusively, group Sk1 disclosed reduction in ICP before internal jugular veins compression withholding. CONCLUSIONS: This study elucidates that CrCP reliably changes in accordance with ICP, being useful to indicate ideal CPP in neurocritical settings. In the early days after DC, cerebrovascular resistance seems to remain elevated, despite exacerbated arterial blood pressure responses in efforts to maintain CPP stable. Patients with ABI with no need of surgical procedures appear to remain with more effective ICP compensatory mechanisms when compared with those who underwent neurosurgical interventions.

Noninvasive intracranial pressure waveforms for estimation of intracranial hypertension and outcome prediction in acute brain-injured patients.

Analysis of intracranial pressure waveforms (ICPW) provides information on intracranial compliance. We aimed to assess the correlation between noninvasive ICPW (NICPW) and invasively measured intracranial pressure (ICP) and to assess the NICPW prognostic value in this population. In this cohort, acute brain-injured (ABI) patients were included within 5 days from admission in six Intensive Care Units. Mean ICP (mICP) values and the P2/P1 ratio derived from NICPW were analyzed and correlated with outcome, which was defined as: (a) early death (ED); survivors on spontaneous breathing (SB) or survivors on mechanical ventilation (MV) at 7 days from inclusion. Intracranial hypertension (IHT) was defined by ICP > 20 mmHg. A total of 72 patients were included (mean age 39, 68% TBI). mICP and P2/P1 values were significantly correlated (r = 0.49, p < 0.001). P2/P1 ratio was significantly higher in patients with IHT and had an area under the receiving operator curve (AUROC) to predict IHT of 0.88 (95% CI 0.78-0.98). mICP and P2/P1 ratio was also significantly higher for ED group (n = 10) than the other groups. The AUROC of P2/P1 to predict ED was 0.71 [95% CI 0.53-0.87], and the threshold P2/P1 > 1.2 showed a sensitivity of 60% [95% CI 31-83%] and a specificity of 69% [95% CI 57-79%]. Similar results were observed when decompressive craniectomy patients were excluded. In this study, P2/P1 derived from noninvasive ICPW assessment was well correlated with IHT. This information seems to be as associated with ABI patients outcomes as ICP.Trial registration: NCT03144219, Registered 01 May 2017 Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03144219 .

Liver transplant recipients infected with SARS-CoV-2 in the early postoperative period: Lessons from a single center in the epicenter of the pandemic.

The impact of coronavirus disease-19 (COVID-19) in liver recipients remains largely unknown. Most data derive from small retrospective series of patients transplanted years ago. We aimed to report a single-center case series of five consecutive patients in the early postoperative period of deceased-donor liver transplantation who developed nosocomial COVID-19. Two patients presented important respiratory discomfort and eventually died. One was 69 years old and had severe coronary disease. She rapidly worsened after COVID-19 diagnosis on 9th postoperative day. The other was 67 years old with non-alcoholic steatohepatitis, who experienced prolonged postoperative course, complicated with cytomegalovirus infection and kidney failure. He was diagnosed on 36th postoperative day and remained on mechanical ventilation for 20 days, ultimately succumbing of secondary bacterial infection. The third, fourth, and fifth patients were diagnosed on 10th, 11th, and 18th postoperative day, respectively, and presented satisfactory clinical evolution. These last two patients were severely immunosuppressed, since one underwent steroid bolus for acute cellular rejection and another also used anti-thymocyte globulin for treating steroid-resistant rejection. Our novel experience highlights that COVID-19 may negatively impact the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID-19 nosocomial spread in the early postoperative period.

The effects of acute kidney injury in a multicenter cohort of high-risk surgical patients.

BACKGROUND AND OBJECTIVES: Patients who develop post-operative acute kidney injury (AKI) have a poor prognosis, especially when undergoing high-risk surgery. Therefore, the objective of this study was to evaluate the outcome of patients with AKI acquired after non-cardiac surgery and the possible risk factors for this complication. METHODS: A multicenter, prospective cohort study with patients admitted to intensive care units (ICUs) after non-cardiac surgery was conducted to assess whether they developed AKI. The patients who developed AKI were then compared to non-AKI patients. RESULTS: A total of 29 ICUs participated, of which 904 high-risk surgical patients were involved in the study. The occurrence of AKI in the post-operative period was 15.8%, and the mortality rate of post-operative AKI patients at 28 days was 27.6%. AKI was strongly associated with 28-day mortality (OR = 2.91; 95% CI 1.51-5.62; p = 0.001), and a higher length of ICU and hospital stay (p < 0.001). Independent factors for the risk of developing AKI were pre-operative anemia (OR = 7.01; 95% CI 1.69-29.07), elective surgery (OR = 0.45; 95% CI 0.21-0.97), SAPS 3 (OR = 1.04; 95% CI 1.02-1.06), post-operative vasopressor use (OR = 2.47; 95% CI 1.34-4.55), post-operative infection (OR = 8.82; 95% CI 2.43-32.05) and the need for reoperation (OR= 7.15; 95% CI 2.58-19.79). CONCLUSION: AKI was associated with the risk of death in surgical patients and those with anemia before surgery, who had a higher SAPS 3, needed a post-operative vasopressor, or had a post-operative infection or needed reoperation were more likely to develop AKI post-operatively.

Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.

Importance: Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective: To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants: Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions: Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures: The primary end point was 90-day survival. Results: Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11; P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance: Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration: ClinicalTrials.gov Identifier: NCT02875873.

Impact of perioperative hemodynamic optimization therapies in surgical patients: economic study and meta-analysis.

BACKGROUND: Several studies suggest that hemodynamic optimization therapies can reduce complications, the length of hospital stay and costs. However, Brazilian data are scarce. Therefore, the objective of this analysis was to evaluate whether the improvement demonstrated by hemodynamic optimization therapy in surgical patients could result in lower costs from the perspective of the Brazilian public unified health system. METHODS: A meta-analysis was performed comparing surgical patients who underwent hemodynamic optimization therapy (intervention) with patients who underwent standard therapy (control) in terms of complications and hospital costs. The cost-effectiveness analysis evaluated the clinical and financial benefits of hemodynamic optimization protocols for surgical patients. The analysis considered the clinical outcomes of randomized studies published in the last 20 years that involved surgeries and hemodynamic optimization therapy. Indirect costs (equipment depreciation, estate and management activities) were not included in the analysis. RESULTS: A total of 21 clinical trials with a total of 4872 surgical patients were selected. Comparison of the intervention and control groups showed lower rates of infectious (RR = 0.66; 95% CI = 0.58-0.74), renal (RR = 0.68; 95% CI = 0.54-0.87), and cardiovascular (RR = 0.87; 95% CI = 0.76-0.99) complications and a nonstatistically significant lower rate of respiratory complications (RR = 0.82; 95% CI = 0.67-1.02). There was no difference in mortality (RR = 1.02; 95% CI = 0.80-1.3) between groups. In the analysis of total costs, the intervention group showed a cost reduction of R$396,024.83-BRL ($90,161.38-USD) for every 1000 patients treated compared to the control group. The patients in the intervention group showed greater effectiveness, with 1.0 fewer days in the intensive care unit and hospital. In addition, there were 333 fewer patients with complications, with a consequent reduction of R$1,630,341.47-BRL ($371,173.27-USD) for every 1000 patients treated. CONCLUSIONS: Hemodynamic optimization therapy is cost-effective and would increase the efficiency of and decrease the burden of the Brazilian public health system.

Early detection of acute kidney injury in the perioperative period of liver transplant with neutrophil gelatinase-associated lipocalin.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients undergoing liver transplant (LT) and is associated with high morbidity and mortality. We aim to evaluate the pattern of urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) elevation during the perioperative period of LT and to assess it as a prognostic marker for AKI progression, need for dialysis and mortality. METHODS: We assessed NGAL levels before induction of anesthesia, after portal reperfusion and at 6, 18, 24, and 48 h after surgery. Patients were monitored daily during the first week after LT. RESULTS: Of 100 enrolled patients undergoing liver transplant, 59 developed severe AKI based on the KDIGO serum creatinine (sCr) criterion; 34 were dialysed, and 21 died within 60 days after LT. Applying a cut-off value of 136 ng/ml, UNGAL values 6 h after surgery was a good predictor of AKI development within 7 days after surgery, having a positive predictive value (PPV) of 80% with an AUC of 0.76 (95% CI 0.67-0.86). PNGAL at 18 h after LT was also a good predictor of AKI in the first week, having a PPV of 81% and AUC of 0.74 (95% CI 0.60-0.88). Based on PNGAL and UNGAL cut-off criteria levels, time to AKI diagnosis was 28 and 23 h earlier than by sCr, respectively. The best times to assess the need for dialysis were 18 h after LT by PNGAL and 06 h after LT by UNGAL. CONCLUSION: In conclusion, the plasma and urine NGAL elevation pattern in the perioperative period of the liver transplant can predict AKI diagnosis earlier. UNGAL was an early independent predictor of AKI development and need for dialysis. Further studies are needed to assess whether the clinical use of biomarkers can improve patient outcomes. TRIAL REGISTRATION: Registered at Clinical Trials ( clinicaltrials.gov ) in March 24th, 2014 by title "Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)" and identifier NCT02095431, retrospectively registered.

Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases.

BACKGROUND: Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVE: The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS: Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS: In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913). MAIN CONCLUSIONS: YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

A pragmatic multi-center trial of goal-directed fluid management based on pulse pressure variation monitoring during high-risk surgery.

BACKGROUND: Intraoperative fluid therapy guided by mechanical ventilation-induced pulse-pressure variation (PPV) may improve outcomes after major surgery. We tested this hypothesis in a multi-center study. METHODS: The patients were included in two periods: a first control period (control group; n = 147) in which intraoperative fluids were given according to clinical judgment. After a training period, intraoperative fluid management was titrated to maintain PPV < 10% in 109 surgical patients (PPV group). We performed 1:1 propensity score matching to ensure the groups were comparable with regard to age, weight, duration of surgery, and type of operation. The primary endpoint was postoperative hospital length of stay. RESULTS: After matching, 84 patients remained in each group. Baseline characteristics, surgical procedure duration and physiological parameters evaluated at the start of surgery were similar between the groups. The volume of crystalloids (4500 mL [3200-6500 mL] versus 5000 mL [3750-8862 mL]; P = 0.01), the number of blood units infused during the surgery (1.7 U [0.9-2.0 U] versus 2.0 U [1.7-2.6 U]; P = 0.01), the fraction of patients transfused (13.1% versus 32.1%; P = 0.003) and the number of patients receiving mechanical ventilation at 24 h (3.2% versus 9.7%; P = 0.027) were smaller postoperatively in PPV group. Intraoperative PPV-based improved the composite outcome of postoperative complications OR 0.59 [95% CI 0.35-0.99] and reduced the postoperative hospital length of stay (8 days [6-14 days] versus 11 days [7-18 days]; P = 0.01). CONCLUSIONS: In high-risk surgeries, PPV-directed volume loading improved postoperative outcomes and decreased the postoperative hospital length of stay. TRIAL REGISTRATION: ClinicalTrials.gov Identifier; retrospectively registered- NCT03128190.

Lung Perfusion and Ventilation During Cardiopulmonary Bypass Reduces Early Structural Damage to Pulmonary Parenchyma.

BACKGROUND: It is unclear whether maintaining pulmonary perfusion and ventilation during cardiopulmonary bypass (CPB) reduces pulmonary inflammatory tissue injury compared with standard CPB where the lungs are not ventilated and are minimally perfused. In this study, we tested the hypothesis that maintenance of lung perfusion and ventilation during CPB decreases regional lung inflammation, which may result in less pulmonary structural damage. METHODS: Twenty-seven pigs were randomly allocated into a control group only submitted to sternotomy (n = 8), a standard CPB group (n = 9), or a lung perfusion group (n = 10), in which lung perfusion and ventilation were maintained during CPB. Hemodynamics, gas exchanges, respiratory mechanics, and systemic interleukins (ILs) were determined at baseline (T0), at the end of 90 minutes of CPB (T90), and 180 minutes after CPB (T180). Bronchoalveolar lavage (BAL) ILs were obtained at T0 and T180. Dorsal and ventral left lung tissue samples were examined for optical and electron microscopy. RESULTS: At T90, there was a transient reduction in PaO2/FIO2 in CPB (126 ± 64 mm Hg) compared with the control and lung perfusion groups (296 ± 46 and 244 ± 57 mm Hg; P < 0.001), returning to baseline at T180. Serum ILs were not different among the groups throughout the study, whereas there were significant increases in BAL IL-6 (P < 0.001), IL-8 (P < 0.001), and IL-10 (P < 0.001) in both CPB and lung perfusion groups compared with the control group. Polymorphonuclear counts within the lung tissue were smaller in the lung perfusion group than in the CPB group (P = 0.006). Electron microscopy demonstrated extrusion of surfactant vesicles into the alveolar spaces and thickening of the alveolar septa in the CPB group, whereas alveolar and capillary histoarchitecture was better preserved in the lung perfusion group. CONCLUSIONS: Maintenance of lung perfusion and ventilation during CPB attenuated early histologic signs of pulmonary inflammation and injury compared with standard CPB. Although increased compared with control animals, there were no differences in serum or BAL IL in animals receiving lung ventilation and perfusion during CPB compared with standard CPB.

Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock.

INTRODUCTION: We investigated whether treatment with terlipressin during recovery from hypotension due to haemorrhagic shock (HS) is effective in restoring cerebral perfusion pressure (CPP) and brain tissue markers of water balance, oxidative stress and apoptosis. METHODS: In this randomised controlled study, animals undergoing HS (target mean arterial pressure (MAP) 40 mmHg for 30 minutes) were randomised to receive lactated Ringer's solution (LR group; n =14; volume equal to three times the volume bled), terlipressin (TERLI group; n =14; 2-mg bolus), no treatment (HAEMO group; n =12) or sham (n =6). CPP, systemic haemodynamics (thermodilution technique) and blood gas analyses were registered at baseline, shock and 5, 30, 60 (T60), 90 and 120 minutes after treatment (T120). After the animals were killed, brain tissue samples were obtained to measure markers of water balance (aquaporin-4 (AQP4)), Na(+)-K(+)-2Cl(-) co-transporter (NKCC1)), oxidative stress (thiobarbituric acid reactive substances (TBARS) and manganese superoxide dismutase (MnSOD)) and apoptotic damage (Bcl-x and Bax). RESULTS: Despite the HS-induced decrease in cardiac output (CO) and hyperlactataemia, resuscitation with terlipressin recovered MAP and resulted in restoration of CPP and in cerebral protection expressed by normalisation of AQP4, NKCC1, TBARS and MnSOD expression and Bcl-x/Bax ratio at T60 and T120 compared with sham animals. In the LR group, CO and blood lactate levels were recovered, but the CPP and MAP were significantly decreased and TBARS levels and AQP4, NKCC1 and MnSOD expression and Bcl-x/Bax ratio were significantly increased at T60 and T120 compared with the sham group. CONCLUSIONS: During recovery from HS-induced hypotension, terlipressin was effective in normalising CPP and cerebral markers of water balance, oxidative damage and apoptosis. The role of this pressor agent on brain perfusion in HS requires further investigation.

Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 µg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 µg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline.

Evaluation of Simplified Acute Physiology Score 3 performance: a systematic review of external validation studies.

INTRODUCTION: Simplified Acute Physiology Score 3 (SAPS 3) was the first critical care prognostic model developed from worldwide data. We aimed to systematically review studies that assessed the prognostic performance of SAPS 3 general and customized models for predicting hospital mortality in adult patients admitted to the ICU. METHODS: Medline, Lilacs, Scielo and Google Scholar were searched to identify studies which assessed calibration and discrimination of general and customized SAPS 3 equations. Additionally, we decided to evaluate the correlation between trial size (number of included patients) and the Hosmer-Lemeshow (H-L) statistics value of the SAPS 3 models. RESULTS: A total of 28 studies were included. Of these, 11 studies (42.8%) did not find statistically significant mis-calibration for the SAPS 3 general equation. There was a positive correlation between number of included patients and higher H-L statistics, that is, a statistically significant mis-calibration of the model (r = 0.747, P <0.001). Customized equations for major geographic regions did not have statistically significant departures from perfect calibration in 9 of 19 studies. Five studies (17.9%) developed a regional customization and in all of them this new model was not statistically different from a perfect calibration for their populations. Discrimination was at least very good in 24 studies (85.7%). CONCLUSIONS: Statistically significant departure from perfect calibration for the SAPS 3 general equation was common in validation studies and was correlated with larger studies, as should be expected, since H-L statistics (both C and H) are strongly dependent on sample size This finding was also present when major geographic customized equations were evaluated. Local customizations, on the other hand, improved SAPS 3 calibration. Discrimination was almost always very good or excellent, which gives excellent perspectives for local customization when a precise local estimate is needed.

Improving perioperative care in low-resource settings with goal-directed therapy: a narrative review.

Perioperative Goal-Directed Therapy (PGDT) has significantly showed to decrease complications and risk of death in high-risk patients according to numerous meta-analyses. The main goal of PGDT is to individualize the therapy with fluids, inotropes, and vasopressors, during and after surgery, according to patients' needs in order to prevent organic dysfunction development. In this opinion paper we aimed to focus a discussion on possible alternatives to invasive hemodynamic monitoring in low resource settings.

Catecholamine concentration as a predictor of mortality in emergency surgical patients.

BACKGROUND: Trauma and emergency surgery are major causes of morbidity and mortality. The objective of this study was to determine whether serum levels of epinephrine and norepinephrine are associated with aging and mortality. METHODS: This was a prospective observational cohort study conducted in a surgical critical care unit. We included 90 patients who were admitted for postoperative care, because of major trauma, or both. We collected demographic and clinical variables, as well as serum levels of epinephrine and norepinephrine. RESULTS: For patients in the > 60-year age group, the use of vasoactive drugs was found to be associated with an undetectable epinephrine level (OR [95% CI] = 6.36 [1.12, 36.08]), p = 0.05). For the patients with undetectable epinephrine levels, the in-hospital mortality was higher among those with a norepinephrine level ≥ 2006.5 pg/mL (OR [95% CI] = 4.00 [1.27, 12.58]), p = 0.03). CONCLUSIONS: There is an association between age and mortality. Undetectable serum epinephrine, which is more common in older patients, could contribute to poor outcomes. The use of epinephrine might improve the clinical prognosis in older surgical patients with shock.

Adverse events leading to intensive care unit admission in a low-and-middle-income-country: A prospective cohort study and a systematic review.

INTRODUCTION: Adverse events (AE) are frequent in critical care and could be even more prevalent in LMIC due to a shortage of ICU beds and Human resources. There is limited data on how relevant AE are among the reasons for ICU admission, being all of which published by High-Income-Countries services. Our main goal is to describe the rate of adverse events-related ICU admissions and their preventability in a LMIC scenario, comparing our results with previous data. METHODS: This was a prospective cohort study, during a one-year period, in two general ICUs from a tertiary public academic hospital. Our exposure of interest was ICU admission related to an AE in adult patients, we further characterized their preventability and clinical outcomes. We also performed a systematic review to identify and compare previous published data on ICU admissions due to AE. RESULTS: Among all ICU admissions, 12.1% were related to an AE (9.8% caused by an AE, 2.3% related but not directly caused by an AE). These ICU admissions were not associated with a higher risk of death, but most of them were potentially preventable (70.9% of preventability rate, representing 8.6% of all ICU admissions). The meta-analysis resulted in a proportion of ICU admissions due to AE of 11% (95% CI 6%-16%), with a preventability rate of 54% (95% CI 42%-66%). CONCLUSIONS: In this prospective cohort, adverse events were a relevant reason for ICU admission. This result is consistent with data retrieved from non-LMIC as shown in our meta-analysis. The high preventability rate described reinforces that quality and safety programs could work as a tool to optimize scarce resources.