Search

Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design

Background Combination therapy with angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m 2 of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of ≥30 ml per minute per 1.73 m 2 if the initial estimated GFR was ≥60 ml per minute per 1.73 m 2 or a decline of ≥50% if the initial estimated GFR was

Summary Background and objectives This study examined the relationship between health-related quality of life and subsequent mortality among AKI survivors treated with renal replacement therapy. Design, setting, participants, & measurements Multivariable Cox regression models were used to assess the associations between Health Utilities Index Mark 3 (HUI3) and ambulation, emotion, cognition, and pain scores at 60 days and all-cause mortality at 1 year in 60-day AKI survivors (n=439 with evaluable HUI3 assessments) from a randomized multicenter study comparing less- with more-intensive renal replacement therapies. Results The median 60-day HUI3 index score was 0.32. Patients with evaluable HUI3 data who died between 60 days and 1 year (n=99) were more likely to have lower 60-day median HUI3 scores, higher comorbidity scores, and longer initial hospital stays, and they were more likely to be dialysis-dependent. A 0.1 higher HUI3 index score was associated with a 17% decrease (hazard ratio, 0.83; 95% confidence interval 0.77–0.89) in all-cause mortality after controlling for clinical risk factors. Similar associations were observed for HUI3 ambulation, emotion, cognition, and pain attribute scores. Conclusions Health-related quality of life measured by HUI3 is an independent predictor of mortality among survivors of AKI after adjusting for clinical risk variables. Poor ambulation and other health-related quality of life attributes are also associated with increased risk of death. Health-related quality of life may provide clinicians with additional information to help identify patients at high risk of mortality after AKI that required renal replacement therapy.

The optimal management of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain. The VA/NIH Acute Renal Failure Trail Network Study (ATN Study) tests the hypothesis that a strategy of intensive RRT will decrease 60-day all-cause mortality in critically ill patients with ARF. Dose separation between the two treatment arms is achieved by increasing the frequency of intermittent hemodialysis (IHD) and sustained low efficiency dialysis (SLED) treatments from three times per week to six times per week, and by increasing continuous venovenous hemodiafiltration (CVVHDF) effluent volume from 20 mL/kg/hr to 35 mL/kg/hr. In both treatment arms, subjects convert between IHD and CVVHDF or SLED as hemodynamic status changes over time. This strategy attempts to replicate the conversion between modalities of RRT that occurs in clinical practice. However, in order to implement this strategy, flexible criteria needed to be developed to provide a balance between the need for uniformity of treatment between groups and practitioner discretion regarding modality of RRT to maintain patient safety. In order to address safety and ethical issues similar to those raised by the Office of Human Research Protections in its review of the ARDS Network studies, a survey of practitioner practices was performed and observational data on the management of RRT in comparable critically ill patients with ARF managed outside of the research context is being collected prospectively. These data will help inform the study's DSMB and site IRB's of the relationship between the study's treatment arms and concurrent clinical practice.

Background. Chronically ill older adults constitute a population vulnerable for complications associated with influenza. Study of their immunity to influenza virus may help design better strategies to stimulate protective immune responses. Methods. Immunogenicity of influenza vaccines and immune protection from natural influenza were assessed in older adults with chronic obstructive pulmonary disease as part of a vaccine efficacy trial. Subjects received either trivalent inactivated influenza virus vaccine (TVV) intramuscularly and trivalent live cold-adapted influenza virus vaccine (CAIV-T; n = 1107) intranasally (inl) or TVV and placebo inl (P; n = 1108). Results. In the subsets of study subjects assessed, serum hemagglutination inhibition (HAI) and nasal-wash antihemagglutinin (HA) immunoglobulin (Ig) A and IgG antibody levels and anti-influenza virus CD8 + cytotoxic T lymphocyte activity increased after immunization. Mean postimmunization nasal-wash IgA antibody levels to influenza A H3/HA and B HA were statistically higher in the TVV+CAIV-T group (n = 957) than in the TVV + P group (n = 951). Postimmunization serum HAI and nasal-wash IgA antibodies to influenza A/H3N2 and B viruses were associated with a reduced relative risk for natural influenza infection. Conclusions. TVV + CAIV-T appeared more immunogenic than TVV + P, but the observed difference may be clinically unimportant. Anti-influenza serum and nasal-wash antibodies were associated with immune protection.

Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopidogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos [hazard ratio, 1.98; 95% confidence interval (CI), 1.19 to 3.28; P = 0.007]. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis.

We assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patients with chronic obstructive pulmonary disease (COPD). Subjects ( N =2215) were randomly assigned to receive either TVV intramuscularly (IM) and CAIV-T intranasally (TC), or TVV and placebo (TP). The vaccines were well-tolerated. Efficacy of TC compared to TP was not statistically significant and was 0.16 for any influenza virus strain (95% confidence limit (CL): −0.22, 0.43), 0.26 for A (H3N2) virus (95% CL: −0.17, 0.53), and −0.05 for type B virus (95% CL: −1.13, 0.48). However, there was a possible advantage for TC over TP in reducing respiratory consequences of an influenza season measured by pulmonary function and symptoms at end of study.

A substudy analysis was conducted to determine the clinical characteristics associated with symptomatic, laboratory-documented influenza (LDI) among 2215 veterans with chronic obstructive pulmonary disease who participated in Department of Veterans Affairs Cooperative Study 448 and who received trivalent inactivated influenza virus vaccine with or without intranasal live-attenuated, cold-adapted influenza vaccine. Of 585 evaluable first occurrences of acute respiratory illnesses, 94 (16%) were LDI. Respiratory symptoms of cough, sputum production, and dyspnea occurred in >90% of patients with LDI; 68% had documented or subjective fever, and 81% had myalgias. Stepwise logistic regression identified only fever and myalgia as being statistically associated with LDI. During the influenza outbreak period, the positive predictive value of fever and myalgia was 41%. Clinical criteria were poor predictors of LDI in these older, vaccinated patients with chronic lung disease. Additional studies are warranted to define optimal methods for the diagnosis of influenza among older persons with chronic obstructive pulmonary disease.

Combination antiplatelet agents, particularly aspirin and ticlopidine, have found increased use in the prevention of arterial thrombosis. Clopidogrel, a thienopyridine derivative, like ticlopidine was recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of ischemic events in patients with myocardial infarction, stroke, or peripheral arterial disease and appears to have much less hematologic toxicity than ticlopidine has. Thrombosis of hemodialysis access grafts is a major cause of morbidity in this patient population. Combination antiplatelet agents may be particularly useful in the prevention of hemodialysis access graft thrombosis. In preparation for such a study, we have performed a pharmacodynamic study of the platelet inhibitory effects of clopidogrel in patients on maintenance hemodialysis. Nine chronic hemodialysis patients were studied. Baseline platelet aggregation studies were performed, after which the subjects were begun on clopidogrel 75 mg daily. Platelet aggregation studies were repeated after 14 days of therapy. Drug was stopped and a final set of platelet aggregation studies were performed 7 days later. Because clopidogrel acts by inhibiting adenosine diphosphate (ADP)-induced platelet aggregation, we used ADP as the agonist in the platelet aggregation studies. We also measured the time required to achieve hemostasis after removing the dialysis needles at the termination of a dialysis session. Patients were carefully monitored for any adverse reaction to clopidogrel. Fourteen days' treatment with clopidogrel inhibited ADP-induced platelet aggregation from 48 to 23% with ADP 2 microM (P=0.0113), from 59 to 38% with ADP 5 microM (P=0. 0166), and from 66 to 44% with ADP 10 microM (P=0. 0172). This inhibition of platelet aggregation was reversed 7 days after stopping clopidogrel. Clopidogrel administration did not affect the time required to achieve hemostasis after removal of the dialysis needles. No adverse reactions were noted. No patient had evidence of bleeding, rash or gastro-intestinal (GI) upset. Clopidogrel inhibits ADP-induced platelet aggregation in subjects receiving chronic maintenance hemodialysis. The magnitude of inhibition is similar to that reported in nonuremic subjects with atherosclerosis. This inhibition is reversible within 7 days of discontinuing the drug. No adverse reactions to the drug were noted in this short-term (14-day) trial.

Summary Background and objectives AKI affects approximately 2%–7% of hospitalized patients and >35% of critically ill patients. Survival after AKI may be described as having an acute phase (including an initial hyperacute component) followed by a convalescent phase, which may itself have early and late components. Design, setting, participants, & measurements Data from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study was used to model mortality risk among patients with dialysis-requiring AKI. This study assumed that the mortality hazard can be described by a piecewise log-linear function with change points. Using an average likelihood method, the authors tested for the number of change points in a piecewise log-linear hazard model. The maximum likelihood approach to locate the change point(s) was then adopted, and associated parameters and standard errors were estimated. Results There were 1124 ATN participants with follow-up to 1 year. The mortality hazard of AKI decreased over time with inflections in the rate of decrease at days 4, 42, and 148, with the sharpest change at day 42. The daily rate of decline in the log of the hazard for death was 0.220 over the first 4 days, 0.046 between day 4 and day 42, 0.017 between day 42 and day 148, and 0.003 between day 148 and day 365. Conclusions There appear to be two major phases of mortality risk after AKI: an early phase extending over the first 6 weeks and a late phase from 6 weeks to 1 year. Within the first 42 days, this can be further divided into hyperacute (days 1–4) and acute (days 4–42) phases. After 42 days, there appear to be early (days 42–148) and late (after day 148) convalescent phases. These findings may help to inform the design of AKI clinical trials and assist critical care physicians in prognostic stratification.

Background Nonsteroidal antiinflammatory drugs may be particularly effective against prostaglandin-mediated, post-injury hyperalgesia and related inflammatory pain. However, their usefulness may be limited by their systemic side effects. The current study determined if local effectiveness can be achieved by low-dose intradermal nonsteroidal antiinflamatory drug administration. Methods Ten healthy volunteers were asked to make magnitude estimations of the pain induced by a contact thermal stimulator at 1 degree C increments between 43 and 51 degrees C at three 1 x 1 cm study sites on each forearm during three study phases:(1) baseline; (2) after pretreatment with 10 microl 0.9% saline (n=1 site on each forearm), 0.3 mg ketorolac (n=1 on each forearm), or nothing (n=1 on each forearm); and (3) after "injury" by a mild burn at the ketorolac- and saline-treated sites on one arm or by injection of 10 nmol bradykinin at all three sites on the other arm. The effects of pretreatment on the pain induced by thermal testing were assessed using repeated-measures analysis of variance. Results Pretreatment with ketorolac had a selective effect on the postburn injury hyperalgesia, reducing the increase in pain intensity (P

The authors compared three methods used to measure exposure to environmental tobacco smoke in pregnant women: personal air monitor, urine cotinine, and questionnaire. Environmental tobacco smoke exposure assessment methods were compared for agreement using Cohen's Kappa and the Spearman rank order correlation coefficient. Women who reported exposure had significantly higher levels of air nicotine concentration compared with women who reported no exposure, but urine cotinine did not differ. Air nicotine was more highly correlated with home exposure (r = 0.34) than work exposure (r = 0.18). Urine cotinine correlated with work exposure (r = 0.14) but neither home nor social exposure. Agreement was "fair" (Kappa = 0.29) when self-reported exposure was compared with air monitor, but agreement was "poor" when urine cotinine was compared with self-report (Kappa = 0.08) and air monitor (Kappa = 0.10). In low environmental tobacco smoke exposure environments, all three methods for measuring exposure may have a role, although modification to monitoring protocols will be needed to improve monitoring sensitivity and exposure classification.

Background Although transesophageal echocardiography allows continuous intraoperative cardiac monitoring, the technique has been limited by the lack of a method for realtime, quantitative assessment of cardiac chamber size and systolic function. Automated border detection (ABD), based on an analysis of integrated backscatter, is a new technique that is purported to provide real-time, quantitative assessment of left ventricular (LV) areas and fractional area change (FAC). A prospective investigation was designed to assess the accuracy and trending capability of ABD during continuous intraoperative monitoring. Methods In 16 patients monitored throughout noncardiac surgical procedures, serial real-time estimates of LV end-diastolic area (EDA), end-systolic area (ESA), and FAC by ABD were compared with paired off-line manual measurements made by two experiences echocardiographers. Results There was a high correlation between real-time ABD estimates of LV ESA (r = 0.93), EDA (r = 0.89), and FAC (r = 0.90) to those of the off-line technique. The automated technique systematically underestimated both EDA and ESA, resulting in a small underestimation of FAC. The automated technique demonstrated an accuracy rate of 96% in tracking serial changes in LV area. The technique performed with an 83% sensitivity and 85% specificity for detecting acute changes in LV area. Conclusions This analysis of serial intraoperative echocardiograms demonstrates the accuracy of ABD to estimate LV area in real time and to track serial changes in cardiac area during surgery. Although ABD is an automated technique, application by personnel experienced in its operation and an echocardiographic system that includes lateral-gain adjustment controls are recommended for its optimal performance.

Study Objective: To elucidate risk factors for apnea in preterm infants discharged from the hospital and in full-term healthy infants. To determine the efficacy of real-time cardiopulmonary monitoring versus computerized storage and retrieval for infants at risk. Study Design: Prospective study. Setting: Operating rooms and pediatric patient care units of university medical center. Patients: 27 preterm infants and 20 full-term infants no more than 60 weeks' postconceptional age, who were admitted for elective herniorrhaphy. Interventions: Infants were monitored before and after herniorrhaphy with general anesthesia using an infant apnea impedance monitor, pulse oximetry, and nursing observation. Measurements and Main Results: Demographic information and medical history were correlated with postoperative apnea. The sensitivity and specificity of nursing observation and oximetry were compared with computerized apnea monitors. Five patients (11%, four preterm, one full-term) were apneic postoperatively as recorded by computerized pneumocardiography. Previous apnea history, gestational age at birth, and postconceptional age at operation positively correlated with postoperative apnea. Nursing observation failed to detect 4 of 5 patients with documented apnea (sensitivity 20%, positive predictive value 50%). Pulse oximetry failed to detect 3 of 5 patients with apnea (sensitivity 40%, positive predictive value 66%). Conclusions: Although it is easier to predict postoperative respiratory dysfunction in previously sick or very young infants, absolute predictability for all neonates remains elusive. Clinical monitors with both storage and retrieval capabilities and real-time monitoring increase our ability to detect significant events in children at risk for apnea after herniorrhaphy.

S OF SCIENTIFIC PAPERS FIRST ANNUAL MEETING OF THE SOCIETY FOR TECHNOLOGY IN ANESTHESIA January 18-20, 1991 Orlando, Florida Sponsored by Diatek Corporation, San Diego, California

To assess the current anesthetic management for aspiration of a foreign body into the airway and esophagus of a young child.Questionnaire study.A questionnaire regarding choice of induction technique in a variety of foreign body clinical scenarios was sent to 1,342 anesthesiologists, all members of the Society for Pediatric Anesthesia. The foreign body, either a coin (penny) or a safety pin (open), was positioned on radiography in a variety of anatomic locations. Depending on the foreign body location, the patient was either asymptomatic or exhibited symptoms. Participants indicated their choice of induction for each situation. Of the 1,342 questionnaires mailed, there were 838 respondents (62.4%). Coins and pins in the gastroesophageal tract were managed mostly by a rapid-sequence induction (p0.001). Coins and pins at all levels in the tracheobronchial tree were managed most often by a mask induction with no cricoid pressure (p0.001). Although 14.5% of respondents chose awake and sedated technique for a foreign body in the supraglottic area, few chose this technique for a foreign body in other locations. The type of object did not affect the choice of drugs for induction of anesthesia in most anatomic locations. Respondents with limited pediatric anesthesia experience used inhalation induction much less often than did those with more experience. Multiple-logistic regression analysis showed that both number of years in practice and type of practice (university, private, hybrid) were predictors for the induction.These data indicate that inhalation induction is favored most often for removal of foreign bodies in the airway, while intravenous induction is preferred for removal of foreign bodies in the gastroesophageal tract. In addition, practice type, greater percentage of time spent in pediatric anesthesia, and greater experience are related to a higher likelihood of inhalation induction.

Summary Background and objectives Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score. Design, setting, participants, & measurements Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers. Results The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively. Conclusions Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations.

There is a significant incidence of inguinal hernia in premature infants and the optimal timing of repair is controversial. A high rate of postoperative respiratory complications has been reported in this group. In this study, the records of 47 premature infants (mean gestational age, 30.3 weeks) who underwent herniorrhaphy while still in the neonatal intensive care unit were reviewed in an effort to define those conditions that are independent risk factors for complications. Forty-three percent of infants had complications, including postoperative assisted ventilation (34%), episodes of apnea and/or bradycardia (23%), emesis and cyanosis with first feeding (6%), and requirement for postoperative reintubation (4%). Although low gestational age and postconceptual age at operation, low birth weight for gestational age, and preoperative ventilatory assistance were significantly associated with postoperative complications, only a history of respiratory distress syndrome/bronchopulmonary dysplasia (odds ratio 2.3), a history of patent ductus arteriosus (odds ratio 2.5), and low absolute weight at operation (odds ratio 3.5 for 1,000-g decrease) were independent risk factors for postoperative complication. Despite previous reports citing postconceptual age as the factor having the greatest impact on postoperative complications, these results indicate that a history of respiratory dysfunction and size at operation may be more important predictors of postoperative respiratory dysfunction in preterm infants.

BACKGROUND The pressure rate quotient (PRQ; mean arterial pressure/heart rate [MAP/HR]) less than one (PRQ or = 1 mm) lasting for > 1 min. Transesophageal echocardiography determination of ischemia was worsening of wall motion > or = 1 grade and lasting > 1 min. PRQ < 1 was compared to ECG and/or TEE as a predictor or indicator of myocardial ischemia. RESULTS Electrocardiography ischemia occurred during 230 intervals in 10 patients, and in only 41 of 230 (18%) was PRQ < 1. Transesophageal echocardiography-defined ischemia occurred during 592 intervals in 9 patients, and in 119 of 592 (20%) PRQ < 1. Compared to ECG and TEE, PRQ < 1 had a low sensitivity (21%) and poor positive predictive value (25%). CONCLUSIONS Pressure rate quotient < 1 is an unreliable indicator and predictor of myocardial ischemia when evaluated by ECG, TEE, and the combination of these modalities in patients undergoing coronary artery bypass graft surgery.

The US Department of Veterans Affairs (VA) Cooperative Studies Program has been conducting comparative effectiveness clinical trials for nearly 4 decades in many disease areas, including cardiovascular disease/surgery, diabetes mellitus, mental health, neurologic disorders, cancer, infectious diseases, and rheumatoid arthritis. The features that have made this program advantageous for conducting comparative effectiveness clinical trials are described along with methodological considerations for future trials based on lessons learned from its experience conducting these types of studies. Some of the lessons learned involve managing risk factors, clinical equipoise, patient preferences, evolving technology, the use of usual care as a comparator and pharmaceutical issues related to study drug blinding. These issues are not unique to the VA but can play an important role in enabling valid comparisons between treatments that may have differences in delivery or mechanisms of action and could affect the execution and feasibility of conducting a clinical trial with a comparative effectiveness aim. We also outline some future directions for comparative effectiveness clinical trials.

Little is known about the prevalence of mucosal antibodies induced by infection with human coronaviruses (HCoV), including HCoV-229E and -OC43 and recently described strains (HCoV-NL63 and -HKU1). By enzyme-linked immunosorbent assay, we measured anti-HCoV IgG antibodies in serum and IgA antibodies in nasal wash specimens collected at seven U.S. sites from 105 adults aged 50 years and older (mean age, 67 ± 9 years) with chronic obstructive pulmonary disease. Most patients (95 [90%]) had at least one more chronic disease. More patients had serum antibody to each HCoV strain (104 [99%] had antibody to HCoV-229E, 105 [100%] had antibody to HCoV-OC43, 103 [98%] had antibody to HCoV-NL63, and 96 [91%] had antibody to HCoV-HKU1) than had antibody to each HCoV strain in nasal wash specimens (12 [11%] had antibody to HCoV-229E, 22 [22%] had antibody to HCoV-OC43, 8 [8%] had antibody to HCoV-NL63, and 31 [31%] had antibody to HCoV-HKU1), respectively ( P < 0.0001). The proportions of subjects with IgA antibodies in nasal wash specimens and the geometric mean IgA antibody titers were statistically higher for HCoV-OC43 and -HKU1 than for HCoV-229E and -NL63. A higher proportion of patients with heart disease than not had IgA antibodies to HCoV-NL63 (6 [16%] versus 2 [3%]; P = 0.014). Correlations were highest for serum antibody titers between group I strains (HCoV-229E and -NL63 [ r = 0.443; P < 0.0001]) and between group II strains (HCoV-OC43 and -HKU1 [ r = 0.603; P < 0.0001]) and not statistically significant between HCoV-NL63 and -OC43 and between HCoV-NL63 and -HKU1. Patients likely had experienced infections with more than one HCoV strain, and IgG antibodies to these HCoV strains in serum were more likely to be detected than IgA antibodies to these HCoV strains in nasal wash specimens.

Background and objectives: Health-related quality of life (HRQOL) after acute kidney injury (AKI) is an area of great importance to patients. It was hypothesized that HRQOL after AKI would relate to intensity of dialysis during AKI and dialysis dependence at follow-up. Design, setting, participants, & measurements: The Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was a multicenter, prospective, randomized trial of intensive versus less intensive renal replacement therapy in critically ill patients with AKI. Of 1124 participants, 415 survived at least 60 days and completed the Health Utilities Index (HUI), which measures 8 health attributes and calculates an overall HRQOL score, also called a utility score. How strongly pre–intensive care unit (ICU) health, severity of illness, hospital course, intensity of dialysis, and outcome were associated with 60-day HUI scores was assessed, after adjustment for demographics. Results: The overall HUI score was 0.40 0.37, indicating severely compromised health utility and was associated with only admission from home and hospital and ICU length of stay (LOS). Ambulation was better among those with a shorter hospital and ICU LOS. Better cognition was associated with dialysis independence and with fewer comorbid chronic illnesses. Emotion was associated with only hospital LOS. Pain was associated with ICU LOS. Conclusions: Health utility was low in this cohort of patients after AKI, and intensity of dialysis did not affect subsequent health utility. The effects of a lengthy hospitalization generally outweighed the effects of delayed recovery of kidney function on HRQOL after AKI. Clin J Am Soc Nephrol 5: 1366–1372, 2010. doi: 10.2215/CJN.02570310

OBJECTIVE To assess the effects of heart rate, right ventricular systolic performance (ejection fraction), chamber dimensions, and flow rate (cardiac index) on the reproducibility of algorithm-derived triplicate thermodilution right ventricular ejection fraction measurements. DESIGN Prospective study; combined hemodynamic and echocardiographic clinical evaluation. SETTING Operating room in a university hospital. PATIENTS Twenty-one coronary artery bypass graft patients. MEASUREMENTS AND MAIN RESULTS The right atrial delivery site was positioned by analysis of transduced pressure waveform and echocardiographic imaging of tracer agitated saline cavitations. Measurement reproducibility was quantified by determining the variation (standard deviation) within 101 triplicate thermodilution measurement sets. There was no significant relationship between measurement reproducibility and estimates of right atrial area (21.6 +/- 6.9 cm2), diameter (5.1 +/- 0.8 cm) and supero-inferior length (5.1 +/- 0.9 cm) and right ventricular maximal minor axis diastolic diameter (4.21 +/- 1.05 cm). Reproducibility was also unrelated to right ventricular end-diastolic volume index (97.9 +/- 32.7 mL/m2) and cardiac index (2.9 +/- 0.9 L/min/m2). Measurement reproducibility was directly related to mean right ventricular ejection fraction (0.39 +/- 0.14) and inversely related to heart rate (80.8 +/- 18.6 beats/min) (p < .01 and < .001, respectively). CONCLUSIONS Thermodilution-derived right ventricular ejection fraction measurement reproducibility was unrelated to estimates of right atrial and ventricular dimensions and cardiac index. Measurement reproducibility was a direct function of right ventricular systolic performance and an indirect function of heart rate. Measurement should be interpreted with these constraints in mind.

Forceful intravascular injection of crystalloid causes microbubble (cavitation) formation. The resulting ultrasound-opaque medium is widely used in echocardiography as a source of contrast. The following study was performed to determine the feasibility of using antegrade crystalloid cardioplegic solution as a transesophageal two-dimensional echocardiographic imaging agent to evaluate aortic valve integrity. In patients with preexisting aortic regurgitation (n = 12), cardioplegic solution administration (driving pressure 150 to 200 mm Hg) was associated with the appearance of intracardiac cavitations in 12 of 12 patients. Among patients without preexisting valve dysfunction (n = 22), intracardiac cavitations were manifested in 20 of 22, with extension of the cavitations to the left atrium in 17. Associated cardiac dimensions (left ventricular outflow tract area and left ventricular diameter) did not exceed preceding cardiopulmonary bypass values in these patients (2.0 +/- 1.6 cm2 versus 2.6 +/- 1.2 cm2 and 1.4 +/- 0.7 cm versus 1.5 +/- 0.8 cm, respectively). It was concluded that antegrade crystalloid cardioplegic solution can be used as an echocardiographic contrast agent in this context. The inability to establish a relationship between the extent of cardioplegic intracardiac penetration and left ventricular dimensional changes limits the technique, as presently employed, to qualitative analysis of valve dysfunction.

To define better the clinical presentation and perioperative outcome in children undergoing adenotonsillectomy (T&A) for relief of upper airway obstruction (UAO), we reviewed the hospital records of 60 consecutive, otherwise normal children aged 12 years or younger. Seven patients with trisomy 21, neurologic impairments, or preoperative corpulmonale were excluded. Intraoperative and postoperative complications were experienced by 15 (34%) and 13 (25%), respectively, of the 53 children with preoperative UAO. The most severe complications comprised pulmonary edema and prolonged postoperative oxyhemoglobin desaturation. Multivariate logistic regression analysis found a history of prematurity and/or low birth weight to be the most significant risk factors related to the occurrence of complications. Twenty-eight % of the study population had a history of prematurity and they had approximately 85% of the perioperative complications seen in children with UAO undergoing T&A. Other significant risk factors included adenoidal facies and evidence of respiratory distress at the time of surgery. It appears that T&A poses significant risk for children with UAO who were born prematurely and have evidence of abnormal facial development or respiratory distress preoperatively. © 1992 Wiley-Liss, Inc.

Perioperative myocardial ischemia is associated with an increased risk of perioperative myocardial infarction (PMI). Several attempts have been made to define intraoperative hemodynamic predictors of myocardial ischemia. In a canine preparation with coronary stenosis, a pressure rate quotient (PRQ = mean arterial pressure/heart rate) less than one (PRQ less than 1) indicated subendocardial myocardial ischemia. The authors tested this hypothesis in patients undergoing elective coronary artery bypass graft operation (CABG), using electrocardiogram (ECG) ST-segment changes (leads II/V5) to diagnose myocardial ischemia. Sixty (n = 60) patients having CABG surgery were prospectively studied before initiation of cardiopulmonary bypass. Calibrated ECG leads II and V5 (diagnostic mode) were monitored continuously and recorded with the use of a Hewlett-Packard computer ST-segment analyzer. In addition, arterial and pulmonary artery pressures were monitored. Ischemia was defined as new-onset ST deviation (greater than or equal to 1 mm from the baseline ECG). ECG and hemodynamic data were stored at 2-min intervals for subsequent computer analysis. Serial creatinine phosphokinase (CPK) X MB (%) determinations and 12-lead ECGs were collected for the initial 3 postoperative days. Of the 3,463 intervals (2 min) available for study, 3,322 (96%) were satisfactorily recorded for 60 patients. Ischemia occurred during 65 intervals in 9 patients (9 of 60), of which only 34% (22 of 65) were associated with a PRQ less than 1 (P less than 0.01). In contrast, there were 466 intervals during which PRQ was less than 1, but without ECG evidence of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes mellitus is associated with fetal growth acceleration and retardation. These aberrations in fetal growth seem to be influenced by a variety of factors including vascular disease, glycemic control, hypertension and smoking. In order to characterize fetal growth under the above conditions, longitudinal sonographic evaluations were performed in 52 pregnant, insulin-dependent diabetic women with the usual monitoring of the patients' metabolic control. Regression analyses revealed that vascular disease and glycemic conditions were the most important influences for growth, with manifestation beyond the second trimester. With stringent glucose control (mean whole blood less than or equal to 100 mg/dl) in the absence of vasculopathy (white classes A, B, C), fetal growth was similar to that in normal pregnancies. In the presence of vasculopathy (white classes D and FR), growth was reduced, especially when near-normal glycemic levels were achieved. Conversely, in poorly controlled diabetic women, enhanced fetal growth were observed in patients with and without vasculopathy. No aberrations in fetal growth were observed, however, before the third trimester. The findings of our study demonstrate that vasculopathy and glycemia are dominant and independent regulators of fetal growth. However, their influences are not manifested in growth changes before the third trimester.

Background: Data on current practices for management of renal replacement therapy (RRT) in acute kidney injury (AKI) are limited, particularly with regard to the dosing of therapy. Design, setting, participants, and measurements: A survey was conducted of practitioners at the 27 study sites that participate in the Veterans Affairs/National Institutes of Health Acute Renal Trial Network (ATN) Study before initiation of patient enrollment for ascertainment of the local prevailing practices for management of RRT in critically ill patients with AKI. Surveys were returned from 130 practitioners at 26 of 27 study sites; the remaining study site provided aggregate data. Results: Intermittent hemodialysis and continuous RRT were the most commonly used modalities of RRT, with sustained low-efficiency dialysis and other “hybrid” treatments used in fewer than 10% of patients. Intermittent hemodialysis was most commonly provided on a thrice-weekly or every-other-day schedule, with only infrequent assessment of the delivered dosage of therapy. Most practitioners reported that they did not dose continuous RRT on the basis of patient weight. The average prescribed dosage of therapy corresponded to a weight-based dosage of no more than 20 to 25 ml/kg per h. Conclusions: These results provide insight into clinical management of RRT and provide normative data for evaluation of the design of ongoing clinical trials.

Our objective was to compare self-reported health-related quality of life (HRQOL) for U.S. veterans with multiple sclerosis (MS) on disease-modifying agents with provider reports of HRQOL from standard disability measures. We conducted a 3-year prospective observational study of 204 subjects who used interferon beta or glatiramer acetate and compared subjects' responses on the Veterans Short-Form 36 (VSF-36) (36-item short-form functional status assessment for veterans) with the Kurtzke Expanded Disability Status Scale (EDSS) and the Functional System (FS) scales, which are standard MS disability scales. EDSS and FS scores were significantly correlated with some VSF-36 domains (physical function [r = -0.57], role physical [r = -0.37], and physical component summary [r = -0.40]) and weakly correlated with other domains. HRQOL scores did not predict disability or compliance with therapy. We observed decrements in HRQOL at relatively low disability levels. HRQOL measures directly associated with physical function were correlated with standard MS disability scales. Researchers need to clarify the role of HRQOL in clinical outcomes assessment, as shown by the lack of outcome sensitivity and predictive value of the VSF-36.

The authors describe a quality-assurance-oriented database program designed for an intraoperative transesophageal echocardiography monitoring service. Entry data include patient and operation demographics and two-dimensional echocardiographic, saline-contrast, and color flow/pulsed Doppler assessments of the heart and great vessels. A statistical analysis component allows for comparison of intraoperative interpretations with those of an external reviewer 'gold standard' on a field-by-field basis. This provides an objective means for quantifying expertise in each individual aspect of the patient examination sequence. Such self-appraisal data are essential for delineating the status and tracking the progress of service being provided. >

This study determined whether the development of delayed ischemic sequelae due to cocaine use-after the return of arterial blood pressure (BP) and heart rate to near-baseline values-may be attributable to regional vasoconstriction which persists beyond the acute systemic hemodynamic response. Five cocaine-using volunteers received intravenous infusions of saline placebo and cocaine 0.50 mg/kg several days apart in a double-blinded cross-over design. The intensity and duration of the cocaine-induced decrease in peripheral blood flow (as documented by laser Doppler flowmetry of the finger) were compared to the increases in BP (obtained with a Dinamap [R]) and heart rate using paired t-test and repeated-measures analysis of variance. A significant increase in BP and a significant decrease in finger flow were noted by the first time point (5 min). Within 15 min, cocaine induced a 36% +/- 5% increase in BP and a 73% +/- 18% decline in finger flow (P < 0.05 for difference between percent change in BP and percent change in flow). Dinamapsystolic and Dinamapdiastolic returned to within 15% of baseline within 30 min, while finger flow remained more than 50% below baseline for the remainder of the 60-min study period (P < 0.05). Changes in heart rate paralleled those in BP. Except for isolated cases of documented coronary vasoconstriction in patients presenting with complications after cocaine use, this study is the first to document the persistence of cocaine-induced vasoconstriction of a sensitive vascular bed beyond the hypertensive response. It thus helps to explain the development of ischemic injury after cocaine use despite a stable rate-pressure product. (Anesth Analg 1997;84:46-50)

Objective: To determine predictors and behavioral outcomes of preoperative anxiety in children undergoing surgery. Design: A prospective, longitudinal study. Setting: A university children's hospital. Participants: One hundred sixty-three children, 2 to 10 years of age (and their parents), who underwent general anesthesia and elective surgery. Main Outcome Measures: In the preoperative holding area, anxiety level of the child and parents was determined using self-reported and independent observational measures. At separation to the operating room, the anxiety level of the child and parents was rated again. Postoperative behavioral responses were evaluated 3 times (at 2 weeks, 6 months, and 1 year). Results: A multiple regression model (R 2 =0.58, F=6.4, P =.007) revealed that older children and children of anxious parents, who received low Emotionality, Activity, Sociability, and Impulsivity (EASI) ratings for activity, and with a history of poor-quality medical encounters demonstrated higher levels of anxiety in the preoperative holding area. A similar model (R 2 =0.42, F=8.6, P =.001) revealed that children who received low EASI ratings for activity, with a previous hospitalization, who were not enrolled in day care, and who did not undergo premedication were more anxious at separation to the operating room. Overall, 54% of children exhibited some negative behavioral responses at the 2-week follow-up. Twenty percent of the children continued to demonstrate negative behavior changes at 6-month follow-up, and, in 7.3% of the children, these behaviors persisted at 1-year follow-up. Nightmares, separation anxiety, eating problems, and increased fear of physicians were the most common problems at 2-week follow-up. Multivariate analysis demonstrated that child's age, number of siblings, and immediate preoperative anxiety of the child and mother predicted later behavioral problems. Conclusions: Variables such as situational anxiety of the mother, temperament of the child, age of the child, and quality of previous medical encounters predict a child's preoperative anxiety. Although immediate negative behavioral responses develop in a relatively large number of young children following surgery, the magnitude of these changes is limited, and long-term maladaptive behavioral responses develop in only a small minority. Arch Pediatr Adolesc Med. 1996;150:1238-1245

BACKGROUND Cutaneous laser Doppler flowmetry enables monitoring of changes in skin perfusion by quantifying the phase shift of laser light induced by moving red blood cells under a fiberoptic probe. It thus can identify the presence of and response to a vasoconstrictive stimulus. However, aspects of the technique must be defined before it can be used with maximum effectiveness. We evaluated the responses of two different laser Doppler outputs, the concentration of moving blood cells (CMBC) and red cell flux (CMBC times cell velocity), and the responses at two sites of probe application, the finger and forearm, during systemic infusions of phenylephrine. METHODS AND RESULTS Eight healthy volunteers were monitored with a brachial blood pressure cuff, ECG, and laser Doppler flowmeter probes applied to the palmar surface of the fourth finger and volar forearm of the arm opposite the pressure cuff. After baseline readings were obtained, the subjects received three 10-minute intravenous infusions of phenylephrine at rates of 0.4, 0.8, and 1.6 micrograms.kg-1.min-1. The two parameters, flux and CMBC, trended similarly. Flux and CMBC at the finger declined significantly in response to each infusion (P < .05 using repeated-measures ANOVA with Duncan's multiple range test). In contrast, flux and CMBC of the forearm had highly variable responses, with an overall increase during each infusion (P < .05 for % delta of forearm versus % delta of finger readings during the 0.4 microgram.kg-1.min-1 infusion). Heart rate declined significantly during each infusion, consistent with a baroreceptor-mediated response, even though systolic and diastolic blood pressures each increased by less than 2 mm Hg during the 0.4 microgram.kg-1.min-1 infusion. CONCLUSIONS As expected, laser Doppler readings at the finger decreased during infusion of an alpha 1-agonist. Although, like the digital vessels, forearm vessels have the potential to constrict, the increases in forearm readings suggest that these vessels are highly susceptible to homeostatic responses. The increase in CMBC (a parameter that is sensitive primarily to local changes in vascular caliber) suggested vasodilation of the underlying vessels. The forearm vasodilation and the concomitant decline in heart rate most likely represented vagally mediated baroreceptor activity, which was altered even though blood pressure changed minimally during the 0.4 microgram.kg-1.min-1 infusion. Thus, integrated assessment of skin perfusion at the finger and forearm may provide valuable information about the direct and indirect effects of a vasoactive stimulus. The present application of laser Doppler flowmetry suggests activation of vasodilatory reflexes despite minimal changes in blood pressure.

Study Objective: To determine whether elimination of intraoperative dextrose-containing infusions affects post—cardiopulmonary bypass hyperglycemia in pediatric patients. Design: Randomized, unblinded, saline-controlled study of perioperative glucose infusions in children undergoing cardiac surgery. Setting: Cardiac surgery suite and pediatric intensive care unit (ICU) of a university medical center. Patients: 33 consecutive, nondiabetic children undergoing cardiac surgery with deep hypothermia over an 8-month period. Interventions: Group A (n = 16) received only normal saline infusions intraoperatively, and Group B (n = 17) received 5% dextrose and lactated Ringer's solution exclusively. Blood glucose was sampled immediately after induction of anesthesia, prior to cardiopulmonary bypass (CPB), after separation from CPB, on arrival in the ICU, and the morning of the first postoperative day. Data were analyzed using Student's t -test for independent samples, paired t -test, and analysis of variance, with p Measurements and Main Results : Although moderate elevations in blood glucose (mean less than 165 mgldl) after CPB were present in Group A, significantly higher levels (mean greater than 250 mg/dl) were noted in Group B. No children were hypoglycemic (glucose less than 40 mg/dl). Glucose levels were normal in both groups on the morning of the first postoperative day despite patients' having received continuous dextrose infusions in the ICU and the presumed stress of emergence from anesthesia. Conclusions: Extreme postbypass hyperglycemia can be controlled by eliminating intra-operative dextrose infusions. Hypoglycemia, an unlikely event, can easily be avoided by regular blood sampling, which is facilitated by the routine placement of arterial catheters.

Intraoperative myocardial ischemia is associated with an increased risk of a perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery. If reversible physiologic variables could be identified that are indicators of myocardial ischemia, treatment might be instituted early to prevent cardiac morbidity. In patients undergoing elective coronary artery bypass graft surgery, we evaluated the relationship between several premorbid patient characteristics, selected hemodynamic variables, intraoperative myocardial ischemia, and a PMI. In addition we evaluated these selected hemodynamic variables as intraoperative indicators of myocardial ischemia. The following variables were evaluated: heart rate,80 beats/min; systolic arterial blood pressure,160 mm Hg; systolic arterial blood pressure,80 mm Hg; mean arterial blood pressure,60 mm Hg; pulmonary artery diastolic pressure,18 mm Hg; a 5 mm Hg increase in pulmonary artery diastolic pressure; rate pressure product,12,000 beats/min.mm Hg; and a pressure rate quotient,1.0 mm Hg/beats/min. The premorbid patient characteristics selected were previous myocardial infarction, recent myocardial infarction (within 1 wk of surgery), type and number of coronary lesions, beta-blocker therapy, and calcium blocker therapy. One hundred consecutive (n = 100) patients for elective coronary artery bypass graft surgery were studied prospectively before the initiation of cardiopulmonary bypass (CPB). Patients were monitored with a Hewlett Packard computer ST segment analyzer using leads II and V5. Ischemia was defined as the new onset of ST segment deviation ofor = 1 mm from the baseline electrocardiogram (ECG) (preinduction) for at least 2 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty coronary artery revascularization patients, aged 58 ± 15 years, were studied intraoperatively to define the impact of Doppler-defined tricuspid regurgitation on measurement of thermodilution right ventricular ejection fraction (50 msec response pulmonary artery catheter). Right ventricular function was also estimated using a measurement technique independent of flow patterns across the tricuspid valve (transesophageal two-dimensional echocardiographic 5.0 MHz phased-array transducer). Measurements included transverse plane long- and short-axis planimetered area ratio, respectively, and tricuspid annular plane systolic excursion ratio (ratio = end-diastolic minus end-systolic value divided by end-diastolic value). Data were expressed as thermodilution-echocardiographic gradients, ie, thermodilution ejection fraction minus long-axis planimetered area ratio, short-axis planimetered area ratio, and tricuspid annular plane systolic excursion ratio, respectively. Tricuspid regurgitation was quantified by color-flow Doppler perimetry of maximal regurgitation jet area and analysis of transduced right atrial pressure waveform. Doppler estimates were expressed as absolute values and as a function of corresponding atrial area (tricuspid regurgitation index = planimetered jet area divided by right atrial area). Data were obtained following endotracheal intubation, sternotomy, pericardiotomy, cardiopulmonary bypass, and chest closure. Data were evaluated by regression analysis, with separate analyses performed for each time period. Profiles were unassociated with right atrial pressure waveform abnormalities. There was no significant relationship between thermodilution ejection fraction variance values and tricuspid regurgitation jet area or regurgitation index, respectively. In each measurement period, thermodilution-echocardiographic gradients were also unrelated to the tricuspid regurgitation estimates. These findings suggest that transesophageal color-flow Doppler evidence of tricuspid regurgitation, without atrial pressure waveform abnormalities, does not invalidate thermodilution right ventricular ejection fraction data.

To identify and quantitate complications occurring in the postanesthesia care unit (PACU), a prospective study evaluated 18,473 consecutive patients entering a PACU at a university teaching hospital. Using a standardized collection form, the incidence of intraoperative and PACU complications was determined. The combined PACU and intraoperative complication rate was 26.7%. Data showed a PACU complication rate of 23.7%, with an overall intraoperative complication rate of 5.1%. Nausea and vomiting (9.8%), the need for upper airway support (6.9%), and hypotension requiring treatment (2.7%) were the most frequently encountered PACU complications. Patients in whom PACU complications developed were analyzed by ASA physical status. Of all patients experiencing nausea and vomiting (n = 1571), the highest percentage were ASA physical status II patients (n = 831). Likewise, in the group of 1450 patients who demonstrated a need for upper airway support, 792 were ASA physical status II. In patients experiencing a major cardiovascular complication, for example, variables associated with a greater risk of developing any PACU complications were ASA physical status (status II), duration of anesthesia (2-4 h), anesthetic technique, emergency procedures, and certain types of surgical procedures (orthopedic or abdominal). For patients admitted with a temperature of less than 35 degrees C the duration of the PACU stay was 152 +/- 46 min compared with 116 +/- 65 min for patients with a temperature greater than or equal to 36 degrees C (P less than 0.01). In conclusion, events occurring during the PACU period continue to be a source of patient morbidity.

Study Objective : To evaluate the consistency of times to 95% twitch height depression (T 95% ) in groups of patients receiving identical induction and relaxant regimens. Design : Prospective, noncontrolled, blinded study. Setting : Ambulatory sifgical unit at a university medical center. Patients : Seventy-five ASA physical status I and II patients undergoing general endotracheal anesthesia. Interventions : Patients received succinylcholine 1.5 m.g/kg or a nondepolarizing regimen with doses ranging from approximately 1.5 to 6 times the ED 95 , with or without a priming dose. Measurements and Main Results : For each of the eight relaxant regimens used in five or more patients, the intraregimen variability of T 95% (at the adductor pollicis muscle upon ulnas stimulation at 0.1 Hz) was expressed as SD and range, and the individual data points were displayed. There was wide intraregimen variability. For each. regimen, the slowest T 95% was at least 73% longer than the fastest T 95% For the 16 patients receiving a priming dose plus an intubating dose 5 or more tunes the ED 95 the median T 95% was 95 seconds; however, T 95% , was beyond 120 seconds in 5 of tire 16 cases. Conclusions : The wide variability in onset times among subjects receiving the souse regimen indicates that monitoring of neuromuscular response, preferably to a relatively slow rate of neurostimulation, is essential q 'one elects to use moderate to high doses of atracurium and/or vecuronium,for rapid-sequence induction in a patient in wham movement or coughing is unacceptable. Since onset times were not symmetrical about the mean, the magnitude and frequency of unacceptable onset times would not be fully appreciated unless the individual data points were displayed. Such information may be critical when, reporting the suitability of a neuromuscular blocking drug for rapid intubation.

The authors evaluated train-of-four (TOF) fade, as quantified by accelography, in response to neurostimulation at currents ranging from 10 to 60 mA. This was done to determine the range of currents over which measurements of fade remain consistent. In 31 patients (ASA Physical Status 1,2, and 3), anesthesia was induced with fentanyl, midazolam, and thiopental and was maintained with isoflurane and 66% nitrous oxide in oxygen. Surface stimulating electrodes were placed over the ulnar nerve, and an acceleration transducer was placed on the thumb. Succinylcholine was administered to facilitate tracheal intubation; after neuromuscular recovery, a bolus of vecuronium (0.01-0.05 mg.kg-1) and an infusion (0.25-1.5 micrograms.kg-1.min-1) were administered. After documentation of a stable TOF ratio, accelographic TOF responses were quantified in response to 200-microseconds stimulation at 10, 15, 20, 30, 40, 50, and 60 mA, in random order. A total of 95 data sets were collected at different depths of blockade. The TOF ratios maintained intercurrent consistency (P = not significant by nonparametric repeated measures analysis of variance), except at currents near the fourth-twitch (T4) threshold current. This inconsistency was eliminated by testing at greater than or equal to 10 mA above threshold. TOF ratios obtained at 10 mA above T4 threshold correlated highly with those at 60 mA (Spearman r value = 0.94). The authors conclude that the TOF ratio is consistent over a wide range of stimulating currents and that testing with submaximal currents can be performed reliably at greater than or equal to 10 mA above the T4 threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. Results Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P = 0.47). There was no significant difference between the two groups in the duration of renalreplacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. Conclusions Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)

Determination of the optimal dose of renal replacement therapy in critically ill patients with acute kidney injury has been controversial. Questions have recently been raised regarding the design and execution of the US Department of Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) Study, which demonstrated no improvement in 60-day all-cause mortality with more intensive management of renal replacement therapy. In the present article we present our rationale for these aspects of the design and conduct of the study, including our use of both intermittent and continuous modalities of renal support, our approach to initiation of study therapy and the volume management during study therapy. In addition, the article presents data on hypotension during therapy and recovery of kidney function in the perspective of other studies of renal support in acute kidney injury. Finally, we address the implications of the ATN Study results for clinical practice from the perspective of the study investigators.

This study documented gastric fluid acidity in ambulatory surgical patients 30-120 min after they had taken a 300-mg tablet of ranitidine, as changes specific to this relatively brief dose-to-sampling interval previously had not been delineated. At 20-120 min before outpatient surgery, ranitidine was given with 15 mL of water to 112 ASA physical status I-III adults without increased risk factors for aspiration of acidic gastric contents. After induction of general endotracheal anesthesia, the gastric fluid was aspirated. Volume and pH were compared with a reference group (pH = 1.6 +/- 1; n = 161) that did not receive an H2-antagonist or water. Of 40 patients sampled at 30-60 min after dosing, 26 had pH greater than or equal to 2.5; mean pH was 3.9 +/- 2 (P less than 0.05 vs reference by Wilcoxon signed rank and chi 2 tests). Beyond 90 min, 28 of 28 patients had a pH greater than or equal to 2.5, with a mean of 6.3 +/- 1. No significant differences were noted with respect to mean gastric volume. We conclude that in patients without additional risk factors, oral ranitidine consistently prevents acid production when it is administered more than 90 min before induction of anesthesia.

Intensive treatment of insulin-dependent diabetes mellitus during pregnancy often normalizes plasma glucose levels. However, it is unclear whether this adversely affects other metabolic fuels that are essential to normal fetal growth and development. Metabolic studies were conducted after the subjects ingested a standardized mixed meal during each trimester in 7 normal and 15 insulin-dependent diabetic pregnant women. The latter were treated with continuous subcutaneous insulin infusion or multiple injections, which were adjusted to achieve strict glucose control throughout pregnancy. Insulin, alanine, branched-chain amino acids, triglycerides, free fatty acids, and ketones were measured every 15 to 30 minutes before a standardized breakfast and for 150 minutes after the breakfast. Patients with insulin-dependent diabetes mellitus were studied while they received their unusual insulin dosages. Fasting glucose levels (87 +/- 7 mg/dl) and glucose levels 150 minutes after the meal (112 +/- 11 mg/dl) were near normal. However, normoglycemia was achieved at the expense of increased plasma insulin levels (area under insulin response curves, p less than 0.01, vs nondiabetic curves). Nevertheless, fasting and post-prandial plasma branched-chain amino acids, alanine, and free fatty acids were similar in both groups. Fasting cholesterol, triglyceride, and ketone levels were also normalized. We conclude that normalization of circulating amino acids and lipids in conjunction with correction of hyperglycemia may contribute to favorable outcomes in infants of intensively treated diabetic mothers.

The current study evaluated the effects of tetanic stimulation on neuromuscular responses to serial train-of-four (TOF) and double-burst stimulation (DBS). For TOF monitoring (n = 13), a degree of neuromuscular blockade was achieved with an intravenous vecuronium infusion such that the ratio of fourth twitch (T4) to first twitch (T1), T4/T1, was stable at a value between 0.1 and 0.7. Four seconds after a 5-s, 50-Hz tetanic stimulus was delivered, TOF monitoring was resumed at 10-s intervals. Significant changes were noted for T1, T4, and T4/T1, with median increases of 38, 250, and 93%, respectively. The median times for T1, T4, and T4/T1 to return to within 10% of their pretetanic (baseline) values were 34, 43, and 34 s, respectively (P = nonsignificant [NS] among times to recovery). A 100-Hz tetanic stimulus induced 50, 300, and 178% median increases of T1, T4, and T4/T1, while corresponding values for recovery times were 53, 73, and 54 s. For DBS monitoring (n = 14), tetanic stimulation (50-Hz, 5-s) induced 38, 300, and 153% median increases of the DBS3,3 parameters (first response [D1], second response [D2], and their ratio [D2 not equal to D1], respectively). The posttetanic effects on D1, D2, and D2/D1 persisted for 43, 66, and 46 s, respectively. For DBS3,2, median posttetanic (50-Hz, 5-s) increases were 41, 275, and 176%, while corresponding times to recovery were 43, 43, and 43 s. Although the data indicate that the posttetanic percent increase was at least 10 times larger at greater degrees of blockade (T4/T1 = 0.1) than at lesser degrees (T4/T1 = 0.7), all T4/T1 and D2/D1 ratios returned to within 10% of baseline in 125 s or less after 5-s tetanic stimulation.