José Rodolfo Rocco

Prognosis of Critically Ill Patients With Cancer and Acute Renal Dysfunction

PURPOSE To evaluate the outcomes of critically ill patients with cancer and acute renal dysfunction. PATIENTS AND METHODS Prospective cohort study conducted at a 10-bed oncologic medical-surgical intensive care unit (ICU) over a 56-month period. RESULTS Of 975 patients, 309 (32%) had renal dysfunction and were studied. Their mean age was 60.9 +/- 15.9 years; 233 patients (75%) had solid tumors and 76 (25%) had hematologic malignancies. During the ICU stay, 98 patients (32%) received dialysis. Renal dysfunction was multifactorial in 56% of the patients, and the main associated factors were shock/ischemia (72%) and sepsis (63%). Overall hospital and 6-month mortality rates were 64% and 73%, respectively. Among patients who required dialysis, mortality rates were lower in patients who received dialysis on the first day of ICU in comparison with those who required it thereafter. In a multivariable Cox model, age more than 60 years, uncontrolled cancer, impaired performance status, and more than two associated organ failures were associated with increased 6-month mortality. Renal function was completely re-established in 82% and partially re-established in 12%, and only 6% of survivors required chronic dialysis. CONCLUSION Acute renal dysfunction is frequent in critically ill patients with cancer. Although mortality rates are high, selected patients can benefit from ICU care and advanced organ support. When evaluating prognosis and the appropriateness of dialysis in these patients, older age, functional capacity, cancer status and the severity of associated organ failures are important variables to take into consideration.

Characteristics and outcomes of cancer patients requiring mechanical ventilatory support for >24 hrs*

Objectives:To describe the characteristics of a large cohort of cancer patients receiving mechanical ventilation for >24 hrs and to identify clinical features predictive of in-hospital death. Design:Prospective cohort study. Setting:Ten-bed oncologic medical-surgical intensive care unit. Patients:A total of 463 consecutive patients were included over a 45-month period. Interventions:None. Measurements and Main Results:Data were collected on the day of admission to the intensive care unit. The intensive care unit and hospital mortality rates were 50% and 64%, respectively. There were 359 (78%) patients with solid tumors and 104 (22%) with hematologic malignancies; 35 (8%) patients had leukopenia. Sepsis (63%), coma (15%), invasion or compression by tumor (11%), pulmonary embolism (7%), and cardiopulmonary arrest (6%) were the main reasons for mechanical ventilation. The independent unfavorable risk factors for mortality were older age (odds ratio, 3.09; 95% confidence interval, 1.61–5.93, for patients 40–70 yrs old, and odds ratio, 9.26; 95% confidence interval, 4.16–20.58, for patients >70 yrs old); performance status 3–4 (odds ratio, 2.51; 95% confidence interval, 1.40–4.51); cancer recurrence/progression (odds ratio, 3.43; 95% confidence interval, 1.81–6.53); Pao2/Fio2 ratio <150 (odds ratio, 2.64; 95% confidence interval, 1.40–4.99); Sequential Organ Failure Assessment score (excluding respiratory domain, each 4 points; odds ratio, 2.34; 95% confidence interval, 1.70–3.24); and airway/pulmonary invasion or compression by tumor as a reason for mechanical ventilation (odds ratio, 5.73; 95% confidence interval, 1.92–17.08). Conclusions:Severity of acute organ failures, poor performance status, cancer status, and older age were the main determinants of mortality. The appropriate use of such easily available clinical characteristics may avoid forgoing intensive care for patients with a chance of survival.

Performance of six severity-of-illness scores in cancer patients requiring admission to the intensive care unit: a prospective observational study

IntroductionThe aim of this study was to evaluate the performance of five general severity-of-illness scores (Acute Physiology and Chronic Health Evaluation II and III-J, the Simplified Acute Physiology Score II, and the Mortality Probability Models at admission and at 24 hours of intensive care unit [ICU] stay), and to validate a specific score – the ICU Cancer Mortality Model (CMM) – in cancer patients requiring admission to the ICU.MethodsA prospective observational cohort study was performed in an oncological medical/surgical ICU in a Brazilian cancer centre. Data were collected over the first 24 hours of ICU stay. Discrimination was assessed by area under the receiver operating characteristic curves and calibration was done using Hosmer–Lemeshow goodness-of-fit H-tests.ResultsA total of 1257 consecutive patients were included over a 39-month period, and 715 (56.9%) were scheduled surgical patients. The observed hospital mortality was 28.6%. Two performance analyses were carried out: in the first analysis all patients were studied; and in the second, scheduled surgical patients were excluded in order to better compare CMM and general prognostic scores. The results of the two analyses were similar. Discrimination was good for all of the six studied models and best for Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation III-J. However, calibration was uniformly insufficient (P < 0.001). General scores significantly underestimated mortality (in comparison with the observed mortality); this was in contrast to the CMM, which tended to overestimate mortality.ConclusionNone of the model scores accurately predicted outcome in the present group of critically ill cancer patients. In addition, there was no advantage of CMM over the other general models.

Prevalência e prognóstico dos pacientes com pneumonia associada à ventilação mecânica em um hospital universitário

OBJECTIVE To determine the prevalence of ventilator-associated pneumonia in an intensive care unit, as well as to identify related factors and characterize patient evolution. METHODS This study evaluated 278 patients on mechanical ventilation for more than 24 hours in a university hospital. RESULTS Ventilator-associated pneumonia developed in 38.1% of the patients, translating to 35.7 cases/1000 ventilator-days: 45.3% were caused by gram-negative agents (Pseudomonas aeruginosa accounting for 22%); and multidrug resistant organisms were identified in 43.4%. In the ventilator-associated pneumonia group, time on mechanical ventilation, time to mechanical ventilation weaning, hospital stays and intensive care unit stays were all longer (p < 0.001). In addition, atelectasis, acute respiratory distress syndrome, pneumothorax, sinusitis, tracheobronchitis and infection with multidrug resistant organisms were more common in the ventilator-associated pneumonia group (p < 0.05). Mortality rates in the intensive care unit were comparable to those observed in the hospital infirmary. Associations between ventilator-associated pneumonia and various factors are expressed as odds ratios and 95% confidence intervals: acute sinusitis (38.8; 3.4-441); > 10 days on mechanical ventilation (7.7; 4.1-14.2); immunosuppression (4.3; 1.3-14.3); acute respiratory distress syndrome (3.5; 1.4-9.0); atelectasis (3.0; 1.2-7.3); cardiac arrest (0.18; 0.05-0.66); and upper gastrointestinal tract bleeding (0.07; 0.009-0.62). The variables found to be associated with in-hospital death were as follows: chronic renal failure (26.1; 1.9-350.7); previous intensive care unit admission (15.6; 1.6-152.0); simplified acute physiologic score II > 50 (11.9; 3.4-42.0); and age > 55 years (4.4; 1.6-12.3). CONCLUSION Ventilator-associated pneumonia increased the time on mechanical ventilation and the number of complications, as well as the length of intensive care unit and hospital stays, but did not affect mortality rates.

Bronchopulmonary dysplasia prediction model for 7-day-old infants

Objective: To develop a predictive model capable of identifying which premature infants have the greatest probability of presenting bronchopulmonary dysplasia (BPD), based on assessment at the end of their first week of life. Methods: Data were collected retrospectively from January 1998 to July 2001, and prospectively from August 2001 to July 2003. All children born at the institution with gestational age < 34 weeks and birth weight < 1,500 gwere included. The principal risk factors for BPD were subjected to univariate analysis followed by logistic regression. Significant variables were used to construct a formula to calculate the probability of BPD. The model was calibrated and its discriminative power assessed using receiver operating characteristic (ROC) curves. Between August 2003 and July 2005 the model was then applied to a different population for validation. Results: The sample comprised 247 children, of whom 68 developed BPD, classified as follows: mild = 35 (51.4%), moderate = 20 (29.4%) and severe = 8 (11.7 %). Four variables maintained significance with relation to BPD: gestational age .. 30 weeks, persistent ductus arteriosus, mechanical ventilation > 2 days and loss of > 15% of birth weight on the 7th day of life. Where patients exhibited all of these variables, the model had a 93.7% probability of being correct. Themodelwas further validated when using another sample of 61 newborns; similar figures were obtained. Conclusions: At the end of the first week of life, the predictive model developed from our populationwas capable of identifying newborn infants at increased risk of developing BPD with a high degree of sensitivity.

Colonization with methicillin‐resistant Staphylococcus aureus after liver transplantation

Methicillin‐resistant Staphylococcus aureus (MRSA) is a frequent cause of infection after orthotopic liver transplantation (OLT). Colonization with MRSA is associated with a higher risk of infection. Previous studies have shown a high prevalence of MRSA colonization among OLT candidates. However, the risk of colonization with MRSA after OLT is still unclear. The objective of this study was to estimate the incidence and the factors associated with colonization with MRSA after OLT. This was a prospective cohort study including patients submitted to OLT between the years 2000 and 2002. Surveillance cultures of nasal swab specimens were performed within the 1st 72 hours of hospital admission and, subsequently, on weeks 2, 6, 13, and 26. Patients whose baseline cultures revealed nasal carriage of MRSA were excluded. A total of 60 patients were included in the study. The median follow‐up was 72 days. A total of 9 patients (15%) became colonized. In multiple logistic regression analyses, the use of a urinary catheter for ≥5 days (P = .006), postoperative bleeding at the surgical site (P = .009), and preoperative use of fluoroquinolones (P = .08) were associated with a higher risk of colonization. Patients without any of these risk factors did not become colonized. In conclusion, nasal carriage of MRSA is frequently acquired after OLT. Periodic postoperative screening for MRSA carriage should be an integral component in programs designed to reduce nosocomial MRSA transmission in these patients. Further studies are needed to set up and validate a predictive model that could allow targeting postoperative screening to high‐risk OLT recipients. (Liver Transpl 2005;11:203–209.)

Delirium in postoperative nonventilated intensive care patients: risk factors and outcomes

BackgroundDelirium features can vary greatly depending on the postoperative population studied; however, most studies focus only on high-risk patients. Describing the impact of delirium and risk factors in mixed populations can help in the development of preventive actions.MethodsThe occurrence of delirium was evaluated prospectively in 465 consecutive nonventilated postoperative patients admitted to a surgical intensive care unit (SICU) using the confusion assessment method (CAM). Patients with and without delirium were compared. A multiple logistic regression was performed to identify the main risk factors for delirium in the first 24 h of admission to the SICU and the main predictors of outcomes.ResultsDelirium was diagnosed in 43 (9.2%) individuals and was more frequent on the second and third days of admission. The presence of delirium resulted in longer lengths of SICU and hospital stays [6 days (3–13) vs. 2 days (1–3), p < 0.001 and 26 days (12–39) vs. 6 days (3–13), p <0.001, respectively], as well as higher hospital and SICU mortality rates [16.3% vs. 4.0%, p = 0.004 and 6.5% vs. 1.7%, p = 0.042, respectively]. The risk factors for delirium were age (odds ratio (OR), 1.04 [1.02-1.07]), Acute Physiologic Score (APS; OR, 1.11 [1.04-1.2]), emergency surgery (OR, 8.05 [3.58-18.06]), the use of benzodiazepines (OR, 2.28 [1.04-5.00]), and trauma (OR, 6.16 [4.1-6.5]).ConclusionsDelirium negatively impacts postoperative nonventilated patients. Risk factors can be used to detect high-risk patients in a mixed population of SICU patients.

Modulation of the renin–angiotensin–aldosterone system in sepsis: a new therapeutic approach?

Importance of the field: Severe sepsis is characterized by relative hypotension associated with a high cardiac output, peripheral vasodilation, and organ dysfunction. The renin–angiotensin–aldosterone system (RAAS) is primarily activated to increase blood pressure, but recently potential pro-inflammatory effects of angiotensin II have attracted interest because of the reported association between angiotensin II levels and organ failure and mortality in sepsis. RAAS antagonists could represent a new therapeutic option in this setting. Areas covered in this review: The role of RAAS activation in severe sepsis and septic shock, and the potential benefits (and risks) of using RAAS antagonists. What the reader will gain: Insight into RAAS function in severe sepsis and the potential for RAAS inhibitors to be used as an adjunctive therapy in patients with severe sepsis, with discussion of promising results from animal models of sepsis. Take home message: Use of RAAS antagonists is an emerging therapeutic option in severe sepsis because these agents may reduce endothelial damage, organ failure, and mortality. However, timing of administration of RAAS antagonists is important because reduced RAAS function may contribute to refractive hypotension later on in septic shock and benefits of RAAS antagonists seem to be restricted to the early phases of sepsis.

Adrenal function testing in patients with septic shock

IntroductionAdrenal failure (AF) is associated with increased mortality in septic patients. Nonetheless, there is no agreement regarding the best diagnostic criteria for AF. We compared the diagnosis of AF considering different baseline total cortisol cutoff values and Δmax values after low (1 μg) and high (249 μg) doses of corticotropin, we analyzed the impact of serum albumin on AF identification and we correlated laboratorial AF with norepinephrine removal.MethodsA prospective noninterventional study was performed in an intensive care unit from May 2002 to May 2005, including septic shock patients over 18 years old without previous steroid usage. After measurement of serum albumin and baseline total cortisol, the patients were sequentially submitted to 1 μg and 249 μg corticotropin tests with a 60-minute interval between doses. Post-stimuli cortisol levels were drawn 60 minutes after each test (cortisol 60 and cortisol 120). The cortisol 60 and cortisol 120 values minus baseline were called Δmax1 and Δmax249, respectively. Adrenal failure was defined as Δmax249 ≤ 9 μg/dl or baseline cortisol ≤ 10 μg/dl. Other baseline cortisol cutoff values referred to as AF in other studies (≤15, ≤20, ≤25 and ≤34 μg/dl) were compared with Δmax249 ≤ 9 μg/dl and serum albumin influence. Norepinephrine removal was compared with the baseline cortisol values and Δmax249 values.ResultsWe enrolled 102 patients (43 male). AF was diagnosed in 22.5% (23/102). Patients with albumin ≤2.5 g/dl presented a lower baseline total cortisol level (15.5 μg/dl vs 22.4 μg/dl, P = 0.04) and a higher frequency of baseline cortisol ≤25 μg/dl (84% vs 58.3%, P = 0.05) than those with albumin > 2.5 g/dl. The Δmax249 levels and Δmax249 ≤ 9, however, were not affected by serum albumin (14.5 μg/dl vs 18.8 μg/dl, P = 0.48 and 24% vs 25%, P = 1.0). Baseline cortisol ≤ 23.6 μg/dl was the most accurate diagnostic threshold to determine norepinephrine removal according to the receiver operating characteristic curve.ConclusionAF was identified in 22.5% of the studied population. Since Δmax249 ≤ 9 μg/dl results were not affected by serum albumin and since the baseline serum total cortisol varied directly with albumin levels, we propose that Δmax249 ≤ 9 μg/dl, which means Δmax after high corticotropin dose may be a better option for AF diagnosis whenever measurement of free cortisol is not available. Baseline cortisol ≤23.6 μg/dl was the best value for predicting norepinephrine removal in patients without corticosteroid treatment.

Sublingual microcirculatory effects of enalaprilat in an ovine model of septic shock.

Severe sepsis is frequently associated with microcirculatory abnormalities despite seemingly adequate hemodynamic resuscitation. As increased serum angiotensin II levels may play a role in this dysfunction, we evaluated the microcirculatory effects of enalaprilat in an experimental model of septic shock. One hour after injection of 1.5 g/kg body weight of feces into the abdominal cavity, 16 adult female anesthetized, mechanically ventilated sheep were randomized to receive 2.5 mg enalaprilat or saline. When fluid-resistant hypotension (mean arterial pressure, <65 mmHg) developed, norepinephrine was given up to a maximal dose of 3 &mgr;g·kg−1·min−1. The sublingual microcirculation was evaluated using sidestream dark-field videomicroscopy. A cutoff of 20 &mgr;m was used to differentiate small and large vessels. Experiments were pursued until the sheeps spontaneous death or for a maximum of 30 h. There were progressive and significant reductions in the proportion of small perfused vessels and in the microvascular flow index for small vessels (both P < 0.01 for trend) during shock and the first 2 h of norepinephrine infusion in the placebo group, which were prevented by the administration of enalaprilat. There were no differences between treated and placebo groups in global hemodynamic variables, time to shock or median survival time (21.8 [18.6-28.8] vs. 22.9 [21.8-30.0] h; P = 0.45). However, oxygen exchange was worse (PaO2/FiO2 ratio, 224 [128-297] vs. 332 [187-450]; P < 0.05), and creatinine concentrations increased more in the treated group (from 0.51 [0.42-0.75] to 1.19 [0.64-1.50] mg·dL−1; P = 0.04) than in the control group (from 0.55 [0.45-0.62] to 0.78 [0.46-1.78] mg·dL−1; P = 0.12), Enalaprilat therefore prevented the worsening of sublingual microcirculatory variables in this fluid-resuscitated, hyperdynamic model of septic shock, without significant effect on arterial pressure, but with a possible deleterious effect on renal and lung function.