Practice guidelines--an emerging synthetic science.
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Biomedical subjects
Publications and source records attributed to D J Cook.
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We performed a meta-analysis to evaluate whether stress ulcer prophylaxis with histamine-2-receptor antagonists or antacids reduces mortality in critically ill patients. It appears that sucralfate results in a lower incidence of nosocomial pneumonia than either antacids or histamine-2-receptor antagonists. With respect to mortality, strong trends favored sucralfate over both antacids and histamine-receptor antagonists.
BACKGROUND: The aim of this study was to investigate propofol's effect on myocardial contractility and relaxation and examine its underlying mechanism of action in isolated ferret ventricular myocardium. METHODS: The effects of propofol on variables of contractility and relaxation and on the free intracellular Ca++ transient detected with the Ca(++)-regulated photoprotein aequorin were analyzed. Propofol's effects were evaluated in a preparation in which the sarcoplasmic reticulum function was impaired by ryanodine. The effects of propofol's solvent, intralipid, on myocardial contractility, relaxation, and the intracellular Ca++ transient also were examined. RESULTS: Propofol, at concentrations of 10 microM or greater, decreased contractility and, at concentrations of 30 of microns or greater, decreased the amplitude of the intracellular Ca++ transient. At equal peak force, control peak aequorin luminescence in [Ca++]o = 2.25 mM and peak aequorin luminescence in 300 microM [Ca++]o = 2.25 mM and peak aequorin luminescence in 300 microM propofol in [Ca++]o > 2.25 mM did not differ, which suggests that propofol does not alter myofibrillar Ca++ sensitivity. After inactivation of sarcoplasmic reticulum Ca++ release with 1 microM ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca++ influx, propofol caused a decrease in contractility and in the amplitude of the intracellular Ca++ transient. Under these conditions, propofol's relative negative inotropic effect did not differ from that in control muscles not exposed to ryanodine. Propofol's solvent, 10% intralipid, exerted a modest positive inotropic effect in this preparation. The intracellular Ca++ transient was unchanged by intralipid. Neither propofol nor intralipid altered the load sensitivity of relaxation. CONCLUSIONS: These findings suggest that the negative inotropic effect of propofol results from a decrease in intracellular Ca++ availability with no changes in myofibrillar Ca++ sensitivity. At least part of propofol's action is attributable to inhibition of transsarcolemmal Ca++ influx.
OBJECTIVES: To describe the activities of a clinical intensive care unit (ICU) pharmacist and to determine whether pharmacist-initiated consultations lead to changes in drug costs. DESIGN: Prospective, 3-month study. SETTING: A 15-bed, university-affiliated, tertiary care medical-surgical ICU. INTERVENTIONS: The following ICU pharmacist activities were recorded: providing drug information for physician inquiries; providing drug information for nurse inquiries; clarification of drug orders; drug accessibility information; pharmacokinetic consultation; detection and reporting of adverse drug reactions; and pharmacist-initiated therapeutic consultation leading to changes in drug therapy. When changes in drug therapy occurred, drug costs before and after the change were determined. MEASUREMENTS AND MAIN RESULTS: During 54 weekdays, 575 pharmacist interventions occurred (10.7 +/- 5.0 interventions/day). The most common interventions were pharmacist-initiated therapeutic consultations (44.7%, 257/575 of the total), and response to physician requests for drug information (39.0%, 224/575). The most resource-intensive activities were provision of physician drug information and therapeutic consultations (49.6 mins and 35.9 mins per day, respectively). On average, 1.70 hrs (102 mins) per day were spent on all interventions. Therapeutic consultations decreased (47.1%), did not change (42.0%), or increased (10.9%) drug costs for a net savings of $10,010.60 (Canadian) over 3 months, or a projected annual savings of $67,664.24, if clinical pharmacy services were extended to 7 days/wk. CONCLUSIONS: Dedicated ICU pharmacists are crucial healthcare team members in a multidisciplinary ICU. In addition to substantially reducing drug costs, they provide continuity in individualized pharmacotherapeutic care, and serve an important educational function.
OBJECTIVE: To examine the relationship between the formulation of enteral nutrition and nosocomial infection in critical illness. DATA SOURCES: Computerized search of published research and reference list review. STUDY SELECTION: Review of 151 citations. Included are 31 primary studies in which the authors described the formulation of enteral nutrition and its effect on infectious morbidity and mortality rates in critically ill humans or animals. DATA EXTRACTION: Abstraction of the methods of primary studies and the impact of the composition of enteral nutrition on infectious morbidity and mortality rates. DATA SYNTHESIS: There is no evidence that the addition of branch-chain amino acids or nucleotides to enteral nutrition reduces infectious morbidity in animals or humans. Supplementation with fish oil, arginine, or glutamine has a variable impact on survival in animal models; there are no clinical trials in critically ill patients that demonstrate reduced infectious morbidity or mortality rates. Some animal studies suggest that intestinal overgrowth and bacterial translocation may be related to the type of fiber used, or elemental or polymeric formulas. Preliminary evidence suggests that Modular Tube Feeds (an enteral formula developed at the Shriner's Burn Institute, Cincinnati, OH), and a commercially available enteral formula (enhanced with omega-3-fatty acids, arginine, and yeast RNA; Impact, Sandoz Nutrition, Minneapolis, MN) may result in decreased infections in burn and postoperative cancer patients, respectively, but not in critically ill patients. Acidification of enteral feeding results in decreased bacterial colonization of the stomach in critically ill patients. CONCLUSIONS: Insufficient experimental data exist to permit conclusions that enteral nutrition formulations or supplements reduce infectious morbidity and mortality rates, but results are promising enough to warrant further research.
PURPOSE: To determine the association between vesicoureteral reflux (VUR) and the presence of acute pyelonephritis in children with urinary tract infections. MATERIALS AND METHODS: The authors studied 150 consecutive patients less than 5 years of age with their first proved urinary tract infection. All patients underwent renal cortical scintigraphy (with technetium-99m dimercaptosuccinic acid or Tc-99m gluconate) and voiding cystourethrography (VCUG) to identify the presence of cortical defects and VUR, respectively. RESULTS: Of 300 kidneys, 88 (29.3%) had a cortical defect at scintigraphy. Fifty-four of the 88 patients (61%) did not have VUR demonstrated at VCUG. Conversely, 72 of the 300 kidneys (24%) had VUR; of these, 38 (53%) had no cortical defect. The sensitivity of VCUG in helping predict a defect was 38.6%, and the specificity was 82.1%. CONCLUSION: VUR (as shown by VCUG) and renal cortical scintigraphic defects frequently occur independently of each other. Renal cortical scintigraphy may be a more accurate predictor of patients at risk for scarring.
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OBJECTIVE: Defects seen on early cortical scintigrams of the renal cortex in children with urinary tract infection may represent acute inflammatory change or established scar. The purpose of this study was to determine the relationship between these defects and age, sex, the presence and grade of vesicoureteral reflux, and infective organism in a cohort of children examined after their first proved urinary tract infection. SUBJECTS AND METHODS: We prospectively examined 193 consecutive patients less than 5 years old who were seen at the ambulatory pediatric department during a 3-year period and had a first proved urinary tract infection. Children with obstructed or solitary kidneys were excluded. All patients were imaged with scintigraphy of the renal cortex and radiographic voiding cystourethrography within 15 days of diagnosis. The association of age, sex, the presence and grade of vesicoureteral reflux, and infective organism with a defect (acute pyelonephritis or a renal scar) seen on a cortical renal scan was studied. RESULTS: The prevalence of cortical defects was greater in the kidneys of patients less than 2 years old (96/290, 33%) than in older children (16/96, 17%) and greater in those with vesicoureteral reflux (41/92, 45%) than in those without it (71/294, 24%). Vesicoureteral reflux was absent in 63% (71/112) of kidneys with a cortical defect. No association with sex or infective organism was established. As well as having a greater prevalence of cortical defects, 145 (75%) of the 193 urinary tract infections included in the study were in children less than 2 years old. The kidneys of these younger patients also had a greater severity and prevalence of vesicoureteral reflux (74/290, 26%) than did those of older children (18/96, 19%). CONCLUSION: Early cortical defects are associated with an age less than 2 years and vesicoureteral reflux. However, the association of early defects with the presence and grade of vesicoureteral reflux is confounded by the declining prevalence and severity of reflux with age. A significant proportion of cortical defects occur in the absence of vesicoureteral reflux, and the contribution of reflux to scar formation might be less than previously considered.
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Identification of HLA-DR, DQ and DP alleles at the DNA level is an important tool for bone marrow transplantation (BMT). We recently encountered an aplastic anemia patient for whom the ability of molecular HLA typing to utilize alternative sources of DNA proved to be fundamental for her treatment. After repeated failures to obtain HLA typing using peripheral blood, HLA-DR and DQ alleles were identified by molecular techniques utilizing two hairs as a source of DNA, ultimately resulting in successful BMT from a sibling donor. This case clearly illustrates the potential of DNA methodologies for HLA typing in patients whose condition precludes the use of more traditional methods.
OBJECTIVE: To present criteria to aid intensive care workers in the assessment of diagnostic technologies, using the example of bronchoalveolar lavage for the evaluation of ventilator-associated pneumonia. DATA SOURCES: MEDLINE was used to search for articles published from 1969 to the present that concerned diagnostic tests, diagnostic technology, pneumonia, and critically ill patients. STUDY SELECTION: Clinical investigations, case control studies, case series, and experimental data on the use of bronchoalveolar lavage. Studies of diagnostic technology were also included. DATA EXTRACTION: We extracted relevant data in duplicate, independently. DATA SYNTHESIS: Diagnostic technology assessment should begin by establishing the capability of the technology under ideal or laboratory conditions, followed by an exploration of the range of possible uses as well as the accuracy of the test. Bronchoalveolar lavage is a well-established technology for the diagnosis of pneumonia in immunocompromised patients. Studies of the accuracy of bronchoalveolar lavage in ventilator-dependent but nonimmunocompromised patients have shown promising diagnostic accuracy. Accuracy, however, is insufficient for dissemination of a test; an evaluation of the impact of a test on management decisions and, most importantly, on patient outcome, is required. Investigators have not addressed the full impact of bronchoalveolar lavage, and, even if the test is accurate, there are reasons to doubt whether patients will be better off if the test becomes part of routine clinical practice. CONCLUSIONS: We present guidelines for the assessment of diagnostic technology, and apply them to bronchoalveolar lavage for the evaluation of ventilator-associated pneumonia. Bronchoalveolar lavage has been studied in both the laboratory and clinical setting, and the diagnostic sensitivity and specificity of this technique are high. Further randomized trials evaluating management decisions and patient benefit would facilitate decisions regarding the appropriate dissemination of bronchoalveolar lavage.
Recent reports have described cerebral venous oxygen desaturation during and after rewarming from hypothermic cardiopulmonary bypass. Additionally, patients undergoing normothermic cardiopulmonary bypass may be at higher risk for neurologic injury. This study was designed to determine whether patients undergoing normothermic cardiopulmonary bypass are at increased risk for sustained cerebral desaturation. Fifty-two patients undergoing first-time coronary artery bypass grafting were randomized to receive normothermic (37 degrees C, n = 26) or hypothermic (27 degrees C, n = 26) cardiopulmonary bypass. The anesthetic was standardized and alpha-stat pH management was used. A 4F oximetric catheter was placed in the jugular bulb and cerebral venous and radial arterial blood were sampled. Oxygen partial pressure and saturation were measured at six intervals from cerebral venous blood and from radial arterial blood. Patients receiving normothermic cardiopulmonary bypass had lesser values of oxygen partial pressure and saturation in cerebral venous blood than patients subjected to hypothermia during the first 40 minutes of bypass. Cerebral venous desaturation (oxygen saturation in cerebral venous blood of 50% or less) was observed in 54% of patients in the normothermic group and 12% of patients in the hypothermic group during cardiopulmonary bypass. In the normothermic group, cerebral desaturation occurred primarily in early bypass (14 of 26). The three episodes of desaturation in the hypothermic group occurred during rewarming. During cardiopulmonary bypass, the arteriovenous oxygen content difference was greater in the normothermic group than in that in the hypothermic group, suggesting higher oxygen consumption. Differences in glucose utilization during early cardiopulmonary bypass between the groups was also detected. One patient in the hypothermic group had an embolic stroke and subsequently died. There were no other perioperative strokes or deaths in the study population. The present study demonstrates that patients undergoing normothermic cardiopulmonary bypass are at greater risk for cerebral desaturation. Because it is a global assessment, cerebral venous oxygen saturation may be insensitive to focal ischemic events. It remains to be seen whether these differences in cerebral physiologic states translate into differences in clinical outcome.
In summary, then, we can learn three useful things from small clinical trials. First, we can learn when to challenge conventional but untested therapeutic wisdom. Second, because the patient number in any trial is the number of events, rather than the number of study patients, some small trials are so definitively positive that they are sufficient to identify the best therapy. And third, small trials, even when individually inconclusive, can serve as the basis for convincingly conclusive overviews and meta-analyses that carry, and deserve, greater credibility than a single large trial of similar size to their sum.
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OBJECTIVE: To examine the relationship between enteral nutrition (EN) and infection in the critically ill. SETTING: Computerized search of published research and review of relevant reference lists. STUDY SELECTION: 151 citations were reviewed and 39 articles met selection criteria. Primary studies were included if they evaluated EN in critically ill humans and its effect on infectious morbidity and mortality. MEASUREMENTS AND RESULTS: Relevant data were abstracted on the timing and impact of EN on morbidity, the optimal route of administration, composition and pH of EN, and bacterial contamination of EN. The evidence from human studies that EN, particularly early EN, results in reduced septic morbidity as compared to parenteral nutrition is limited to small, unblinded studies with non-rigorous definitions of pneumonia. There is no evidence to support a preference of feeding into the stomach versus the small bowel. The addition of fish oil, arginine, glutamine and fiber to enteral feeds has a variable impact on survival in animal models; there are no trials in critically ill patients that demonstrate a reduction in infectious morbidity and mortality. Acidification of enteral nutrition results in decreased bacterial colonization of the stomach in critically ill patients. Bacterial contamination of enteral nutrition is an important source of infection. CONCLUSIONS: Evidence from experimental data in critically ill patients suggests that enteral nutrition may have a favourable impact on gastrointestinal immunological function and infectious morbidity.