Andrew L. Rosenberg

Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function.

Background:The authors investigated the incidence and risk factors for postoperative acute renal failure after major noncardiac surgery among patients with previously normal renal function. Methods:Adult patients undergoing major noncardiac surgery with a preoperative calculated creatinine clearance of 80 ml/min or greater were included in a prospective, observational study at a single tertiary care university hospital. Patients were followed for the development of acute renal failure (defined as a calculated creatinine clearance of 50 ml/min or less) within the first 7 postoperative days. Patient preoperative characteristics and intraoperative anesthetic management were evaluated for associations with acute renal failure. Thirty-day, 60-day, and 1-yr all-cause mortality was also evaluated. Results:A total of 65,043 cases between 2003 and 2006 were reviewed. Of these, 15,102 patients met the inclusion criteria; 121 patients developed acute renal failure (0.8%), and 14 required renal replacement therapy (0.1%). Seven independent preoperative predictors were identified (P < 0.05): age, emergent surgery, liver disease, body mass index, high-risk surgery, peripheral vascular occlusive disease, and chronic obstructive pulmonary disease necessitating chronic bronchodilator therapy. Several intraoperative management variables were independent predictors of acute renal failure: total vasopressor dose administered, use of a vasopressor infusion, and diuretic administration. Acute renal failure was associated with increased 30-day, 60-day, and 1-yr all-cause mortality. Conclusions:Several preoperative predictors previously reported to be associated with acute renal failure after cardiac surgery were also found to be associated with acute renal failure after noncardiac surgery. The use of vasopressor and diuretics is also associated with acute renal failure.

Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set.

Background:The authors sought to identify the incidence, risk factors, and mortality impact of acute kidney injury (AKI) after general surgery using a large and representative national clinical data set. Methods:The 2005–2006 American College of Surgeons– National Surgical Quality Improvement Program participant use data file is a compilation of outcome data from general surgery procedures performed in 121 US medical centers. The primary outcome was AKI within 30 days, defined as an increase in serum creatinine of at least 2 mg/dl or acute renal failure necessitating dialysis. A variety of patient comorbidities and operative characteristics were evaluated as possible predictors of AKI. A logistic regression full model fit was used to create an AKI model and risk index. Thirty-day mortality among patients with and without AKI was compared. Results:Of 152,244 operations reviewed, 75,952 met the inclusion criteria, and 762 (1.0%) were complicated by AKI. The authors identified 11 independent preoperative predictors: age 56 yr or older, male sex, emergency surgery, intraperitoneal surgery, diabetes mellitus necessitating oral therapy, diabetes mellitus necessitating insulin therapy, active congestive heart failure, ascites, hypertension, mild preoperative renal insufficiency, and moderate preoperative renal insufficiency. The c statistic for a simplified risk index was 0.80 in the derivation and validation cohorts. Class V patients (six or more risk factors) had a 9% incidence of AKI. Overall, patients experiencing AKI had an eightfold increase in 30-day mortality. Conclusions:Approximately 1% of general surgery cases are complicated by AKI. The authors have developed a robust risk index based on easily identified preoperative comorbidities and patient characteristics.

Review of A Large Clinical Series: Association of Cumulative Fluid Balance on Outcome in Acute Lung Injury: A Retrospective Review of the ARDSnet Tidal Volume Study Cohort:

Objective: To evaluate the independent influence of fluid balance on outcomes for patients with acute lung injury. Design: Secondary analysis of a prospective cohort study conducted between March 1996 and March 1999. Setting: The study involved 10 academic clinical centers (with 24 hospitals and 75 Intensive Care Units). Patients: All patients for whom fluid balance data existed (844) from the 902 patients enrolled in the National Heart Lung Blood Institutes ARDS Network ventilator-tidal volume trial. Interventions: The study had no interventions. Measurements/Results: On the first day of study enrollment, 683 patients were, on average, more than 3.5 L in positive fluid balance compared to 161 patients in negative fluid balance (P < .001). Cumulative negative fluid balance on day 4 of the study was associated with an independently lower hospital mortality (OR, 0.50; 95% CI, 0.28-0.89; P < .001) more ventilator and intensive care unit—free days. Conclusions: Negative cumulative fluid balance at day 4 of acute lung injury is associated with significantly lower mortality, independent of other measures of severity of illness.

Who bounces back? Physiologic and other predictors of intensive care unit readmission.

ObjectiveTo determine the influence of changes in acute physiology scores (APS) and other patient characteristics on predicting intensive care unit (ICU) readmission. DesignSecondary analysis of a prospective cohort study. SettingSingle large university medical intensive care unit. PatientsA total of 4,684 consecutive admissions from Janu-ary 1, 1994, to April 1, 1998, to the medical ICU. InterventionsNone. Measurements and Main Results The independent influence of patient characteristics, including daily APS, admission diagnosis, treatment status, and admission location, on ICU readmission was evaluated using logistic regression. After accounting for first ICU admission deaths, 3,310 patients were “at-risk” for ICU readmission and 317 were readmitted (9.6%). Hospital mortality was five times higher (43% vs. 8%;p < .0001), and length of stay was two times longer (16 ± 16 vs. 32 ± 28 days;p < .001) in readmitted patients. Mean discharge APS was significantly higher in the readmitted group compared with the not readmitted group (43 ± 19 vs. 34 ± 18;p > .01). Significant independent predictors of ICU readmission included discharge APS >40 (odds ratio [OR] 2.1; 95% confidence interval [CI] 1.6–2.7;p < .0001), admission to the ICU from a general medicine ward (Floor) (OR 1.9; 95% CI 1.4–2.6;p < .0001), and transfer to the ICU from other hospital (Transfer) (OR 1.7; 95% CI 1.3–2.3;p < .01). The overall model calibration and discrimination were (H-L &khgr;2 = 3.8, df = 8;p = .85) and (receiver operating characteristic 0.67), respectively. ConclusionsPatients readmitted to medical ICUs have significantly higher hospital lengths of stay and mortality. ICU readmissions may be more common among patients who respond poorly to treatment as measured by increased severity of illness at first ICU discharge and failure of prior therapy at another hospital or on a general medicine unit. Tertiary care ICUs may have higher than expected readmission rates and mortalities, even when accounting for severity of illness, if they care for significant numbers of transferred patients.

Cytotoxicity of Local Anesthetics in Human Neuronal Cells

BACKGROUND: In addition to inhibiting the excitation conduction process in peripheral nerves, local anesthetics (LAs) cause toxic effects on the central nervous system, cardiovascular system, neuromuscular junction, and cell metabolism. Different postoperative neurological complications are ascribed to the cytotoxicity of LAs, but the underlying mechanisms remain unclear. Because the clinical concentrations of LAs far exceed their EC50 for inhibiting ion channel activity, ion channel block alone might not be sufficient to explain LA-induced cell death. However, it may contribute to cell death in combination with other actions. In this study, we compared the cytotoxicity of six frequently used LAs and will discuss the possible mechanism(s) underlying their toxicity. METHODS: In human SH-SY5Y neuroblastoma cells, viability upon exposure to six LAs (bupivacaine, ropivacaine, mepivacaine, lidocaine, procaine, and chloroprocaine) was quantitatively determined by the MTT-(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetra-odium bromide) colorimetry assay and qualitatively confirmed by fluorescence imaging, using the LIVE/DEAD® assay reagents (calcein/AM and ethidium homodimer-1). In addition, apoptotic activity was assessed by measuring the activation of caspase-3/-7 by imaging using a fluorescent caspase inhibitor (FLICA™). Furthermore, LA effects on depolarization- and carbachol-stimulated intracellular Ca2+-responses were also evaluated. RESULTS: 1) After a 10-min treatment, all six LAs decreased cell viability in a concentration-dependent fashion. Their killing potency was procaine ≤ mepivacaine < lidocaine < chloroprocaine < ropivacaine < bupivacaine (based on LD50, the concentration at which 50% of cells were dead). Among these six LAs, only bupivacaine and lidocaine killed all cells with increasing concentration. 2) Both bupivacaine and lidocaine activated caspase-3/-7. Caspase activation required higher levels of lidocaine than bupivacaine. Moreover, the caspase activation by bupivacaine was slower than by lidocaine. Lidocaine at high concentrations caused an immediate caspase activation, but did not cause significant caspase activation at concentrations lower than 10 mM. 3) Procaine and chloroprocaine concentration-dependently inhibited the cytosolic Ca2+-response evoked by depolarization or receptor-activation in a similar manner as a previous observation made with bupivacaine, ropivacaine, mepivacaine, and lidocaine. None of the LAs caused a significant increase in the basal and Ca2+-evoked cytosolic Ca2+-level. CONCLUSION: LAs can cause rapid cell death, which is primarily due to necrosis. Lidocaine and bupivacaine can trigger apoptosis with either increased time of exposure or increased concentration. These effects might be related to postoperative neurologic injury. Lidocaine, linked to the highest incidence of transient neurological symptoms, was not the most toxic LA, whereas bupivacaine, a drug causing a very low incidence of transient neurological symptoms, was the most toxic LA in our cell model. This suggests that cytotoxicity-induced nerve injury might have different mechanisms for different LAs and different target(s) other than neurons.

Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery.

Background:The authors sought to determine the incidence and risk factors for perioperative cardiac adverse events (CAEs) after noncardiac surgery using detailed preoperative and intraoperative hemodynamic data. Methods:The authors conducted a prospective observational study at a single university hospital from 2002 to 2006. All American College of Surgeons–National Surgical Quality Improvement Program patients undergoing general, vascular, and urological surgery were included. The CAE outcome definition included cardiac arrest, non-ST elevation myocardial infarction, Q-wave myocardial infarction, and new clinically significant cardiac dysrhythmia within the first 30 postoperative days. Results:Four years of data demonstrated that of 7,740 noncardiac operations, 83 patients (1.1%) experienced a CAE within 30 days. Nine independent predictors were identified (P ≤ 0.05): age ≥ 68, body mass index ≥ 30, emergent surgery, previous coronary intervention or cardiac surgery, active congestive heart failure, cerebrovascular disease, hypertension, operative duration ≥ 3.8 h, and the administration of 1 or more units of packed red blood cells intraoperatively. The c-statistic of this model was 0.81 ± 0.02. Univariate analysis demonstrated that high-risk patients experiencing a CAE were more likely to experience an episode of mean arterial pressure < 50 mmHg (6% vs. 24%, P = 0.02), experience an episode of 40% decrease in mean arterial pressure (26% vs. 53%, P = 0.01), and an episode of heart rate > 100 (22% vs. 34%, P = 0.05). Conclusions:In comparison with current risk stratification indices, the inclusion of intraoperative elements improves the ability to predict a perioperative CAE after noncardiac surgery.

Recent innovations in intensive care unit risk-prediction models

During the past 20 years, ICU risk-prediction models have undergone significant development, validation, and refinement. Among the general ICU severity of illness scoring systems, the Acute Physiology and Chronic Health Evaluation (APACHE), Mortality Prediction Model (MPM), and the Simplified Acute Physiology Score (SAPS) have become the most accepted and used. To risk-adjust patients with longer, more severe illnesses like sepsis and acute respiratory distress syndrome, several models of organ dysfunction or failure have become available, including the Multiple Organ Dysfunction Score (MODS), the Sequential Organ Failure Assessment (SOFA), and the Logistic Organ Dysfunction Score (LODS). Recent innovations in risk adjustment include automatic physiology and diagnostic variable retrieval and the use of artificial intelligence. These innovations have the potential of extending the uses of case-mix and severity-of-illness adjustment in the areas of clinical research, patient care, and administration. The challenges facing intensivists in the next few years are to further develop these models so that they can be used throughout the IUC stay to assess quality of care and to extend them to more specific patient groups such as the elderly and patients with chronic ICU courses.

A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury*

Rationale:Despite recent advances in critical care and ventilator management, acute lung injury and acute respiratory distress syndrome continue to cause significant morbidity and mortality. Granulocyte-macrophage colony stimulating factor may be beneficial for patients with acute respiratory distress syndrome. Objectives:To determine whether intravenous infusion of granulocyte-macrophage colony stimulating factor would improve clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome. Design:A randomized, double-blind, placebo-controlled clinical trial of human recombinant granulocyte-macrophage colony stimulating factor vs. placebo. The primary outcome was days alive and breathing without mechanical ventilatory support within the first 28 days after randomization. Secondary outcomes included mortality and organ failure-free days. Setting:Medical and surgical intensive care units at three academic medical centers. Patients:One hundred thirty individuals with acute lung injury of at least 3 days duration were enrolled, out of a planned cohort of 200 subjects. Interventions:Patients were randomized to receive human recombinant granulocyte-macrophage colony stimulating factor (64 subjects, 250 &mgr;g/M2) or placebo (66 subjects) by intravenous infusion daily for 14 days. Patients received mechanical ventilation using a lung-protective protocol. Measurements and Main Results:There was no difference in ventilator-free days between groups (10.7 ± 10.3 days placebo vs. 10.8 ± 10.5 days granulocyte-macrophage colony stimulating factor, p = .82). Differences in 28-day mortality (23% in placebo vs. 17% in patients receiving granulocyte-macrophage colony stimulating factor (p = .31) and organ failure-free days (12.8 ± 11.3 days placebo vs. 15.7 ± 11.9 days granulocyte-macrophage colony stimulating factor, p = .16) were not statistically significant. There were similar numbers of serious adverse events in each group. Conclusions:In a randomized phase II trial, granulocyte-macrophage colony stimulating factor treatment did not increase the number of ventilator-free days in patients with acute lung injury/acute respiratory distress syndrome. A larger trial would be required to determine whether treatment with granulocyte-macrophage colony stimulating factor might alter important clinical outcomes, such as mortality or multiorgan failure. (ClinicalTrials.gov number, NCT00201409 [ClinicalTrials.gov]).

Optimal Head Rotation for Internal Jugular Vein Cannulation When Relying on External Landmarks

External anatomic landmarks have traditionally been used to approximate the location of the neck blood vessels to optimize central venous cannulation of the internal jugular vein (IJV) while avoiding the common carotid artery (CCA). Head rotation affects vessel orientation, but most landmark techniques do not specify its optimal degree. We simulated catheter insertion via both an anterior and central approach to the right IJV using an ultrasound probe held in the manner of a syringe and needle in 49 volunteers. Increased head rotation from 0°, 15°, 30°, 45°, and 60° to the left of midline was associated with higher probability of a simulated needle contacting the IJV and the CCA. For both approaches, the risk of CCA contact was <10% for head rotations of ≤45°. Increased body surface area (BSA) and body mass index (BMI) were associated with more CCA contact at head rotations of 45° or 60°. To optimize IJV contact while reducing the likelihood of inadvertent contact with the CCA, the head should be rotated no more than 30° in patients with high BMI or BSA, but it may be turned to 60° if BMI or BSA is low.

The importance of bacterial sepsis in intensive care unit patients with acquired immunodeficiency syndrome: implications for future care in the age of increasing antiretroviral resistance.

ObjectiveTo describe the clinical characteristics and outcomes of patients with acquired immunodeficiency syndrome (AIDS) admitted to the intensive care unit (ICU). DesignAn observational cohort study with retrospective chart review. SettingICU of an urban university medical center. PatientsConsecutive ICU admissions of patients with AIDS at an urban university medical center between December 1993 and June 1996. InterventionsNone. Measurements and Main Results For each patient, we recorded ICU admission diagnosis, clinical characteristics, and outcome. Among 129 ICU admissions of patients with AIDS, 102 (79%) were admitted for infections, of which (45%) had infections caused by bacteria. Pseudomonas aeruginosa, Staphylococcus aureus, and other enteric pathogens were the most frequent isolates. Pneumonia accounted for 65% of 102 admissions for infections. Overall hospital mortality was 54%, but mortality was higher (68%) for patients with bacterial sepsis. Neutropenia was associated with differences in unadjusted survival rates, whereas CD4 counts were not. Independent predictors of hospital mortality included increasing acute physiology scores and severity of sepsis. ConclusionsIn our ICU, among patients with AIDS, sepsis resulting from bacterial infection is now a more frequent cause of admission than Pneumocystis carinii pneumonia. Severity of illness and the presence of severe sepsis were the clinical predictors most associated with increased mortality. Patients who are not receiving or responding to highly active antiretroviral therapy may become as likely to be admitted to an ICU with a treatable bacterial infection as with classic opportunistic infections. Therefore, broad-spectrum empirical antibacterial therapy is particularly important when the etiology of infection is uncertain.