Choosing immunomodulating therapies for the treatment of COVID-19: recommendations based on placebo-controlled trial evidence.

BACKGROUND: Immunomodulatory therapy has been extensively studied in randomized clinical trials for the treatment of patients hospitalized for COVID-19 with inconsistent findings. Guideline committees, reviewing the same clinical trial data, have generated different recommendations for immunomodulatory therapy. OBJECTIVES: We hypothesize that trial design differences, specifically whether the study utilized an open-label or placebo-controlled design, accounted for the inconsistent mortality effects reported in clinical trials of immunomodulator therapies for COVID-19. SOURCES: We reviewed COVID-19 treatment guidelines (World Health Organization [WHO], Infectious Diseases Society of America [IDSA] and The National Institutes of Health [NIH]) and identified the meta-analyses associated with glucocorticoids, IL-6 inhibitors, JAK kinase inhibitors, and complement C5a inhibitors that were available to the guideline authors at the time recommendations were either made or updated. CONTENT: We identified a meta-analysis for each of the immunomodulator classes that are included in current COVID-19 treatment guidelines: glucocorticoids [WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, et al. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: A meta-analysis. JAMA. 2021;326:499-518] (cited 419), IL-6 antagonists [WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, et al. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: A meta-analysis. JAMA. 2021;326:499-518] (cited 419), JAK inhibitors [Kramer A, Prinz C, Fichtner F, Fischer AL, Thieme V, Grundeis F, et al. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022;6:CD015209] (cited 34), and complement C5a inhibitors [Tsai CL, Lai CC, Chen CY, Lee HS. The efficacy and safety of complement C5a inhibitors for patients with severe COVID-19: A systematic review and meta-analysis. Expert Rev Anti Infect Ther. 2023;21:77-86] (cited 1). Using the same randomized clinical trials, we evaluated the four meta-analyses accounting for trial design: placebo-controlled or open-label. Glucocorticoids (Risk Ratio [RR] 0.91 [95% CI, 0.49-1.69]), IL-6 inhibitors sarilumab (RR 1.17 [95% CI, 0.96-01.43]), and tocilizumab (RR 0.95 [95% CI, 0.76-1.19]) did not reduce mortality in placebo-controlled trials, whereas baricitinib did confer a large survival benefit (RR 0.65 [95% CI, 0.52-0.81]). The complement C5a inhibitor, vilobelimab, also reduced mortality in a single placebo-controlled trial (RR 0.76 [95% CI, 0.57-1.0]). IMPLICATIONS: Placebo-controlled trial evidence indicates that baricitinib should be the first choice immunomodulator for patients hospitalized for COVID-19 who require any form of oxygen support-low- or high-flow oxygen, non-invasive or invasive ventilation. Vilobelimab warrants study in a large placebo-controlled trial. Treatment guidelines for future pandemics should prioritize the results of placebo-controlled trials.

Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial.

PURPOSE: Trials of tocilizumab in patients with severe COVID-19 pneumonia have demonstrated mixed results, and the role of tocilizumab in combination with other treatments is uncertain. Here we evaluated whether tocilizumab plus remdesivir provides greater benefit than remdesivir alone in patients with severe COVID-19 pneumonia. METHODS: This randomized, double-blind, placebo-controlled, multicenter trial included patients hospitalized with severe COVID-19 pneumonia requiring > 6 L/min supplemental oxygen. Patients were randomly assigned (2:1 ratio) to receive tocilizumab 8 mg/kg or placebo intravenously plus ≤ 10 days of remdesivir. The primary outcome was time from randomization to hospital discharge or "ready for discharge" (defined as category 1, assessed by the investigator on a 7-category ordinal scale of clinical status) to day 28. Patients were followed for 60 days. RESULTS: Among 649 enrolled patients, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. 566 patients (88.2%) received corticosteroids during the trial to day 28. Median time from randomization to hospital discharge or "ready for discharge" was 14 (95% CI 12-15) days with tocilizumab plus remdesivir and 14 (95% CI 11-16) days with placebo plus remdesivir [log-rank P = 0.74; Cox proportional hazards ratio 0.97 (95% CI 0.78-1.19)]. Serious adverse events occurred in 128 (29.8%) tocilizumab plus remdesivir and 72 (33.8%) placebo plus remdesivir patients; 78 (18.2%) and 42 (19.7%) patients, respectively, died by day 28. CONCLUSIONS: Tocilizumab plus remdesivir did not shorten time to hospital discharge or "ready for discharge" to day 28 compared with placebo plus remdesivir in patients with severe COVID-19 pneumonia.

Intra-abdominal hypertension, fluid balance, and adverse outcomes after orthotopic liver transplantation.

BACKGROUND: Intra-abdominal hypertension (IAH) is frequently encountered in critically ill surgical patients. We aimed to evaluate the incidence of IAH after orthotopic liver transplant (OLT) and its impact on organ function, hospital length-of-stay (LOS), and death. METHODS: This prospective, observational, cohort study evaluated consecutive adult patients admitted in the ICU after undergoing OLT. Intra-abdominal pressure (IAP) was measured every 4-6 h for 3 days. Worsening IAP was defined as a gradual increase in IAP over a period of time. Daily fluid balance was the daily sum of all intakes minus the output. RESULTS: IAH was observed in 48% of the patients within the first 3 days after ICU admission, while ACS was diagnosed in 15%. Patients with IAH had a higher positive fluid balance at day 1 (1764 mL [812-2733 mL] vs. 1301 mL [241-1904 mL], p = 0.025). Worsening IAH was associated with fewer days free of organ dysfunction. IAH within 72 h after ICU admission was independently associated with a composite outcome of death or a longer ICU LOS (odds ratio 2.9; CI 95% 1.02-8.25, p = 0.043). CONCLUSION: After OLT, nearly half of the patients presented IAH, that was associated with unfavorable outcomes.

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.

Perioperative hemodynamic management 4.0.

Postoperative complications within 30 days represent the third leading cause of death in the world. Multiple solutions have been proposed to tackle the clinical and economic burden of postoperative complications. They include the optimal fluid and hemodynamic management of patients undergoing major surgery. Technological innovations and a better understanding of cardiovascular physiology underlie the evolution of perioperative hemodynamic management, ranging from the mere normalization of heart rate, blood pressure, and central venous pressure to oxygen delivery maximization with a pulmonary artery catheter and individualized fluid management with esophageal Doppler or pulse contour methods. The concept of personalized hemodynamic management recently emerged and may soon become a reality, because of new technologies enabling noninvasive measurement of cardiac output, not only during and after but also before surgery. The monitoring of microcirculation and tissue perfusion may help to fine tune this approach. Importantly, mortality within 30 days after surgery is 1000 times higher than intraoperative mortality. Therefore, continuous ward monitoring with wireless and wearable sensors may be the next major opportunity to improve patient safety.

Current research priorities in perioperative intensive care medicine.

INTRODUCTION: Surgical treatments are offered to more patients than ever before, and increasingly to older patients with chronic disease. High-risk patients frequently require critical care either in the immediate postoperative period or after developing complications. The purpose of this review was to identify and prioritise themes for future research in perioperative intensive care medicine. METHODS: We undertook a priority setting process (PSP). A panel was convened, drawn from experts representing a wide geographical area, plus a patient representative. The panel was asked to suggest and prioritise key uncertainties and future research questions in the field of perioperative intensive care through a modified Delphi process. Clinical trial registries were searched for on-going research. A proposed "Population, Intervention, Comparator, Outcome" (PICO) structure for each question was provided. RESULTS: Ten key uncertainties and future areas of research were identified as priorities and ranked. Appropriate intravenous fluid and blood component therapy, use of critical care resources, prevention of delirium and respiratory management featured prominently. CONCLUSION: Admissions following surgery contribute a substantial proportion of critical care workload. Studies aimed at improving care in this group could have a large impact on patient-centred outcomes and optimum use of healthcare resources. In particular, the optimum use of critical care resources in this group is an area that requires urgent research.

Outcomes for patients with cancer admitted to the ICU requiring ventilatory support: results from a prospective multicenter study.

BACKGROUND: This study was undertaken to evaluate the clinical characteristics and outcomes of patients with cancer requiring nonpalliative ventilatory support. METHODS: This was a secondary analysis of a prospective cohort study conducted in 28 Brazilian ICUs evaluating adult patients with cancer requiring invasive mechanical ventilation (MV) or noninvasive ventilation (NIV) during the first 48 h of their ICU stay. We used logistic regression to identify the variables associated with hospital mortality. RESULTS: Of 717 patients, 263 (37%) (solid tumors = 227; hematologic malignancies = 36) received ventilatory support. NIV was initially used in 85 patients (32%), and 178 (68%) received MV. Additionally, NIV followed by MV occurred in 45 patients (53%). Hospital mortality rates were 67% in all patients, 40% in patients receiving NIV only, 69% when NIV was followed by MV, and 73% in patients receiving MV only (P < .001). Adjusting for the type of admission, newly diagnosed malignancy (OR, 3.59; 95% CI, 1.28-10.10), recurrent or progressive malignancy (OR, 3.67; 95% CI, 1.25-10.81), tumoral airway involvement (OR, 4.04; 95% CI, 1.30-12.56), performance status (PS) 2 to 4 (OR, 2.39; 95% CI, 1.24-4.59), NIV followed by MV (OR, 3.00; 95% CI, 1.09-8.18), MV as initial ventilatory strategy (OR, 3.53; 95% CI, 1.45-8.60), and Sequential Organ Failure Assessment score (each point except the respiratory domain) (OR, 1.15; 95% CI, 1.03-1.29) were associated with hospital mortality. Hospital survival in patients with good PS and nonprogressive malignancy and without tumoral airway involvement was 53%. Conversely, patients with poor functional capacity and cancer progression had unfavorable outcomes. CONCLUSIONS: Patients with cancer with good PS and nonprogressive disease requiring ventilatory support should receive full intensive care, because one-half of these patients survive. On the other hand, provision of palliative care should be considered the main goal for patients with poor PS and progressive underlying malignancy.

Optimizing perioperative hemodynamics: what is new?

PURPOSE OF REVIEW: Using perioperative goal-directed therapy (GDT) or peroperative hemodynamic optimization significantly reduces postoperative complications and risk of death in patients undergoing noncardiac major surgeries. In this review, we discuss the main changes in the field of perioperative optimization over the last few years. RECENT FINDINGS: One of the key aspects that has changed in the last decade is the shift from invasive monitoring with pulmonary artery catheters (PACs) to less or minimally invasive monitoring systems. The evaluation of intravascular fluid volume deficits has also changed dramatically from the use of static indices to the assessment of fluid responsiveness using either dynamic indices or functional hemodynamic. Finally, attention has been directed toward more restrictive strategies of crystalloids as maintenance fluids. SUMMARY: GDT is safe and more likely to tailor the amount of fluids given to the amount of fluids actually needed. This approach includes assessment of fluid responsiveness and, if necessary, the use of inotropes; moreover, this approach can be coupled with a restrictive strategy for maintenance fluids. These strategies have been increasingly incorporated into protocols for perioperative hemodynamic optimization in high-risk patients undergoing major surgery, resulting in more appropriate use of fluids, vasopressors, and inotropes.

Restrictive strategy of intraoperative fluid maintenance during optimization of oxygen delivery decreases major complications after high-risk surgery.

INTRODUCTION: Optimal fluid management is crucial for patients who undergo major and prolonged surgery. Persistent hypovolemia is associated with complications, but fluid overload is also harmful. We evaluated the effects of a restrictive versus conventional strategy of crystalloid administration during goal-directed therapy in high-risk surgical patients. METHODS: We conducted a prospective, randomized, controlled study of high-risk patients undergoing major surgery. For fluid maintenance during surgery, the restrictive group received 4 ml/kg/hour and the conventional group received 12 ml/kg/hour of Ringer's lactate solution. A minimally invasive technique (the LiDCO monitoring system) was used to continuously monitor stroke volume and oxygen delivery index (DO2I) in both groups. Dobutamine was administered as necessary, and fluid challenges were used to test fluid responsiveness to achieve the best possible DO2I during surgery and for 8 hours postoperatively. RESULTS: Eighty-eight patients were included. The patients' median age was 69 years. The conventional treatment group received a significantly greater amount of lactated Ringer's solution (mean ± standard deviation (SD): 4, 335 ± 1, 546 ml) than the restrictive group (mean ± SD: 2, 301 ± 1, 064 ml) (P < 0.001). Temporal patterns of DO2I were similar between the two groups. The restrictive group had a 52% lower rate of major postoperative complications than the conventional group (20.0% vs 41.9%, relative risk = 0.48, 95% confidence interval = 0.24 to 0.94; P = 0.046). CONCLUSIONS: A restrictive strategy of fluid maintenance during optimization of oxygen delivery reduces major complications in older patients with coexistent pathologies who undergo major surgery. TRIAL REGISTRATION: ISRCTN: ISRCTN94984995.

Early determinants of death due to multiple organ failure after noncardiac surgery in high-risk patients.

BACKGROUND: Prediction of perioperative cardiac complications is important in the medical management of patients undergoing noncardiac surgery. However, these patients frequently die as a consequence of primary or secondary multiple organ failure (MOF), often as a result of sepsis. We investigated the early perioperative risk factors for in-hospital death due to MOF in surgical patients. METHODS: This was a prospective, multicenter, observational cohort study performed in 21 Brazilian intensive care units (ICUs). Adult patients undergoing noncardiac surgery who were admitted to the ICU within 24 hours after operation were evaluated. MOF was characterized by the presence of at least 2 organ failures. To determine the relative risk (RR) of in-hospital death due to MOF, we performed a logistic regression multivariate analysis. RESULTS: A total of 587 patients were included (mean age, 62.4 ± 17 years). ICU and hospital mortality rates were 15% and 20.6%, respectively. The main cause of death was MOF (53%). Peritonitis (RR 4.17, 95% confidence interval [CI] 1.38-12.6), diabetes (RR 3.63, 95% CI 1.17-11.2), unplanned surgery (RR 3.62, 95% CI 1.18-11.0), age (RR 1.04, 95% CI 1 0.01-1.08), and elevated serum lactate concentrations (RR 1.52, 95% CI 1.14-2.02), a high central venous pressure (RR 1.12, 95% CI 1.04-1.22), a fast heart rate (RR 3.63, 95% CI 1.17-11.2) and pH (RR 0.04, 95% CI 0.0005-0.38) on the day of admission were independent predictors of death due to MOF. CONCLUSIONS: MOF is the main cause of death after surgery in high-risk patients. Awareness of the risk factors for death due to MOF may be important in risk stratification and can suggest routes for therapy.

Polymorphisms IL10-819 and TLR-2 are potentially associated with sepsis in Brazilian patients.

Genetic variation in immune response is probably involved in the progression of sepsis and mortality in septic patients. However, findings in the literature are sometimes conflicting or their significance is uncertain. Thus, we investigated the possible association between 12 polymorphisms located in the interleukin-6 (IL6), IL10, TLR-2, Toll-like receptor-4 (TLR-4), tumor necrosis factor-α and tumor necrosis factor-ß (lymphotoxin α--LTA) genes and sepsis. Critically ill patients classified with sepsis, severe sepsis and septic shock and 207 healthy volunteers were analyzed and genotyped. Seven of the nine polymorphisms showed similar distributions in allele frequencies between patients and controls. Interestingly, our data suggest that the IL10-819 and TLR-2 polymorphisms may be potential predictors of sepsis.

Polymorphisms IL10-819 and TLR-2 are potentially associated with sepsis in Brazilian patients

Genetic variation in immune response is probably involved in the progression of sepsis and mortality in septic patients. However, findings in the literature are sometimes conflicting or their significance is uncertain. Thus, we investigated the possible association between 12 polymorphisms located in the interleukin-6 (IL6), IL10, TLR-2, Toll-like receptor-4 (TLR-4), tumor necrosis factor-α and tumor necrosis factor-β (lymphotoxin α - LTA) genes and sepsis. Critically ill patients classified with sepsis, severe sepsis and septic shock and 207 healthy volunteers were analyzed and genotyped. Seven of the nine polymorphisms showed similar distributions in allele frequencies between patients and controls. Interestingly, our data suggest that the IL10-819 and TLR-2 polymorphisms may be potential predictors of sepsis.

Validation of four prognostic scores in patients with cancer admitted to Brazilian intensive care units: results from a prospective multicenter study.

OBJECTIVE: The aim of the present study was to validate the Simplified Acute Physiology Score II (SAPS II) and 3 (SAPS 3), the Mortality Probability Models III (MPM(0)-III), and the Cancer Mortality Model (CMM) in patients with cancer admitted to several intensive care units (ICU). DESIGN: Prospective multicenter cohort study. SETTING: Twenty-eight ICUs in Brazil. PATIENTS: Seven hundred and seventeen consecutive patients (solid tumors 93%; hematological malignancies 7%) included over a 2-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Discrimination was assessed by area under receiver operating characteristic (AROC) curves and calibration by Hosmer-Lemeshow goodness-of-fit test. The main reasons for ICU admission were postoperative care (57%), sepsis (15%) and respiratory failure (10%). The ICU and hospital mortality rates were 21 and 30%, respectively. When all 717 patients were evaluated, discrimination was superior for both SAPS II (AROC = 0.84) and SAPS 3 (AROC = 0.84) scores compared to CMM (AROC = 0.79) and MPM(0)-III (AROC = 0.71) scores (P < 0.05 in all comparisons). Calibration was better using CMM and the customized equation of SAPS 3 score for South American countries (CSA). MPM(0)-III, SAPS II and standard SAPS 3 scores underestimated mortality (standardized mortality ratio, SMR > 1), while CMM tended to overestimation (SMR = 0.48). However, using the SAPS 3 for CSA resulted in more precise estimations of the probability of death [SMR = 1.02 (95% confidence interval = 0.87-1.19)]. Similar results were observed when scheduled surgical patients were excluded. CONCLUSIONS: In this multicenter study, the customized equation of SAPS 3 score for CSA was found to be accurate in predicting outcomes in cancer patients requiring ICU admission.

Characteristics and outcomes of patients with cancer requiring admission to intensive care units: a prospective multicenter study.

OBJECTIVE: To evaluate the characteristics and outcomes of patients with cancer admitted to several intensive care units. Knowledge on patients with cancer requiring intensive care is mostly restricted to single-center studies. DESIGN: : Prospective, multicenter, cohort study. SETTING: Intensive care units from 28 hospitals in Brazil. PATIENTS: A total of 717 consecutive patients included over a 2-mo period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 667 (93%) patients with solid tumors and 50 (7%) patients had hematologic malignancies. The main reasons for intensive care unit admission were postoperative care (57%), sepsis (15%), and respiratory failure (10%). Overall hospital mortality rate was 30% and was higher in patients admitted because of medical complications (58%) than in emergency (37%) and scheduled (11%) surgical patients (p < .001). Adjusting for covariates other than the type of admission, the number of hospital days before intensive care unit admission (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.37), higher Sequential Organ Failure Assessment scores (OR, 1.25; 95% CI, 1.17-1.34), poor performance status (OR, 3.40; 95% CI, 2.19 -5.26), the need for mechanical ventilation (OR, 2.42; 95% CI, 1.51-3.87), and active underlying malignancy in recurrence or progression (OR, 2.42; 95% CI, 1.51-3.87) were associated with increased hospital mortality in multivariate analysis. CONCLUSIONS: This large multicenter study reports encouraging survival rates for patients with cancer requiring intensive care. In these patients, mortality was mostly dependent on the severity of organ failures, performance status, and need for mechanical ventilation rather than cancer-related characteristics, such as the type of malignancy or the presence of neutropenia.

Effects of dobutamine on gut mucosal nitric oxide production during endotoxic shock in rabbits.

BACKGROUND: Dobutamine is the agent of choice for increasing cardiac output during myocardial depression in humans with septic shock. Studies have shown that beta-adrenoceptor agonists influence nitric oxide generation, probably by modulating cyclic adenosine monophosphate. We investigated the effects of dobutamine on the systemic and luminal gut release of nitric oxide during endotoxic shock in rabbits. MATERIAL/METHODS: Twenty anesthetized and ventilated New Zealand rabbits received placebo or intravenous lipopolysaccharide with or without dobutamine (5 micro g/kg/min). Ultrasonic flow probes placed around the superior mesenteric artery and the abdominal aorta continuously estimated the flow. A segment from the ileum was isolated and perfused, and serum nitrate/nitrite levels were measured in the perfusate solution and the serum every hour. RESULTS: The mean arterial pressure decreased with statistical significance in the lipopolysaccharide group but not in the lipopolysaccharide/dobutamine group. The abdominal aortic flow decreased statistically significantly after lipopolysaccharide administration in both groups but recovered to baseline in the lipopolysaccharide/dobutamine group. The flow in the superior mesenteric artery was statistically significantly higher in the lipopolysaccharide/dobutamine group than in the lipopolysaccharide group at 2 hours. The serum nitrate/nitrite levels were higher in the lipopolysaccharide group and lower in the lipopolysaccharide/dobutamine group than those in the control group. The gut luminal perfusate serum nitrate/nitrite level was higher in the lipopolysaccharide group than in the lipopolysaccharide/dobutamine group. CONCLUSIONS: Dobutamine can decrease total and intestinal nitric oxide production in vivo. Those effects seem to be inversely proportional to the changes in blood flow.

Prospective, randomized trial comparing fluids and dobutamine optimization of oxygen delivery in high-risk surgical patients [ISRCTN42445141].

INTRODUCTION: Preventing perioperative tissue oxygen debt contributes to a better postoperative recovery. Whether the beneficial effects of fluids and inotropes during optimization of the oxygen delivery index (DO2I) in high-risk patients submitted to major surgeries are due to fluids, to inotropes, or to the combination of the two is not known. We aimed to investigate the effect of DO2I optimization with fluids or with fluids and dobutamine on the 60-day hospital mortality and incidence of complications. METHODS: A randomized and controlled trial was performed in 50 high-risk patients (elderly with coexistent pathologies) undergoing major elective surgery. Therapy consisted of pulmonary artery catheter-guided hemodynamic optimization during the operation and 24 hours postoperatively using either fluids alone (n = 25) or fluids and dobutamine (n = 25), aiming to achieve supranormal values (DO2I > 600 ml/minute/m2). RESULTS: The cardiovascular depression was an important component in the perioperative period in this group of patients. Cardiovascular complications in the postoperative period occurred significantly more frequently in the volume group (13/25, 52%) than in the dobutamine group (4/25, 16%) (relative risk, 3.25; 95% confidence interval, 1.22-8.60; P < 0.05). The 60-day mortality rates were 28% in the volume group and 8% in the dobutamine group (relative risk, 3.00; 95% confidence interval, 0.67-13.46; not significant). CONCLUSION: In patients with high risk of perioperative death, pulmonary artery catheter-guided hemodynamic optimization using dobutamine determines better outcomes, whereas fluids alone increase the incidence of postoperative complications.

Delayed hemodynamic monitoring with pulmonary artery catheter is a non-essential care in severe sepsis and septico shock

Objective: Prompt adequate antibiotic therapy, eradication of infection, fluids and vasoactive drugs are themain strategies for initial resuscitation of septic shock. Once initial resuscitative efforts are not effective,invasive hemodynamic monitoring (HM) with pulmonary artery catheter (PAC) has been frequently used toguide filling pressures and optimal doses of vasoactive agents. However, the evidence of benefit from PACuse in septic shock is still a matter of debate. We aimed to determine whether early compared to delayplacement of PAC could have influenced outcome.Methods: Retrospective analysis in a 24-bed general ICU tertiary care university hospital. From January 1999to December 2000, patients admitted with severe sepsis and septic shock and having a PAC inserted werestudied. Early invasive HM was defined whenever a PAC was placed in the first 48 hours, and delayedinvasive HM was placed more than 48 hours after the diagnosis of severe sepsis or septic shock. Organ failurewas defined as a SOFA score of > 3 points.Results. Among 104 patients submitted to invasive monitoring with PAC, 56 patients had sepsis. Fifty-twopatients with severe sepsis (5, 9.6 por cento) and septic shock (47, 90.4 por cento) were enrolled. Thirty-six patients (69 por cento) hadearly HM and 16 (21 por cento) delayed HM. Overall in-hospital mortality was 69 por cento. The groups had similar APACHEII score (18.6 ± 8.0, early HM; 18.5 ± 3.8, delayed HM), SOFA score (9.4 ± 3.2, early HM; 9.9 ± 4.4, delayed HM)and number of organs failure (1.6 ± 0.9, early HM; 1.8 ± 1.4, delayed HM) at the onset of severe sepsis/septicshock. The in-hospital mortality rate was significantly higher in delayed HM group (87.5 por cento) compared withearly HM (61.3 por cento) (RR: 0.70, CI 95 por cento 0.50-0.96, p < 0.05). Compared with delayed HM, early HM patientsreceived significantly higher amount of fluids (10.3 ± 3.6 L vs 6.8 ± 3.5 L, p = 0.002) within 48 hours from onsetof severe sepsis/septic shock.Conclusion. Delayed monitoring with PAC patients with severe sepsis/septic shock is associated with a veryhigh risk of death and might be considered a non-essential care.

Descompensaçäo cardíaca pós-intoxicaçäo exógena por estricnina: relato de caso / Cardiac descompensation from exogenous intoxication by strychnine: case report

Apresentamos o caso de um paciente intoxicado por estricnina que evoluiu com Insuficiência Cardíaca Congestiva diagnosticada através de ecocardiograma e parâmetros hemodinâmicos conseguidos através de cateter de Swan-Ganz. A intoxicaçao por estricnina nao é comumente encontrada devido à proibiçao de sua comercializaçao, especial atençao tem sido dada a esta droga devido ao seu uso na manufatura de drogas como a cocaína. Alguns autores mostram que a estricnina age sobre centros vasomotores alterando pressao arterial durante as convulsoes, outros mostraram arritmias durante as convulsoes, mas nao comprovaram a existência de cardiotoxidade pela estricnina. A monitorizaçao hemodinâmica foi de bastante auxílio neste caso nao só no sentido de guiar a terapêutica mas também no diagnóstico diferencial do edema pulmonar que, em se tratando de paciente hígido e jovem poderia facilmente ser rotulado como edema "nao cardiogênico". Embora a intoxicaçao por estricnina seja de altíssima mortalidade, com o suporte hemodinâmico e respiratório adequado proporcionamos uma recuperaçao total do paciente, sem seqüela neurológica, renal e pulmonar.