Pamela R. Roberts

Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: The NASCENT randomized trial

CONTEXT Ventilator-associated pneumonia (VAP) causes substantial morbidity. A silver-coated endotracheal tube has been designed to reduce VAP incidence by preventing bacterial colonization and biofilm formation. OBJECTIVE To determine whether a silver-coated endotracheal tube would reduce the incidence of microbiologically confirmed VAP. DESIGN, SETTING, AND PARTICIPANTS Prospective, randomized, single-blind, controlled study conducted in 54 centers in North America. A total of 9417 adult patients (> or = 18 years) were screened between 2002 and 2006. A total of 2003 patients expected to require mechanical ventilation for 24 hours or longer were randomized. INTERVENTION Patients were assigned to undergo intubation with 1 of 2 high-volume, low-pressure endotracheal tubes, similar except for a silver coating on the experimental tube. MAIN OUTCOME MEASURES Primary outcome was VAP incidence based on quantitative bronchoalveolar lavage fluid culture with 10(4) colony-forming units/mL or greater in patients intubated for 24 hours or longer. Other outcomes were VAP incidence in all intubated patients, time to VAP onset, length of intubation and duration of intensive care unit and hospital stay, mortality, and adverse events. RESULTS Among patients intubated for 24 hours or longer, rates of microbiologically confirmed VAP were 4.8% (37/766 patients; 95% confidence interval [CI], 3.4%-6.6%) in the group receiving the silver-coated tube and 7.5% (56/743; 95% CI, 5.7%-9.7%) (P = .03) in the group receiving the uncoated tube (all intubated patients, 3.8% [37/968; 95% CI, 2.7%-5.2%] and 5.8% [56/964; 95% CI, 4.4%-7.5%] [P = .04]), with a relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; all intubated patients, 34.2% [95% CI, 1.2%-67.9%]). The silver-coated endotracheal tube was associated with delayed occurrence of VAP (P = .005). No statistically significant between-group differences were observed in durations of intubation, intensive care unit stay, and hospital stay; mortality; and frequency and severity of adverse events. CONCLUSION Patients receiving a silver-coated endotracheal tube had a statistically significant reduction in the incidence of VAP and delayed time to VAP occurrence compared with those receiving a similar, uncoated tube. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00148642.

Effect of chain length on absorption of biologically active peptides from the gastrointestinal tract.

Objectives: Protein digestion generates many peptides in the gut lumen. Some of these peptides possess biological effects when tested using in vitro systems. It is clear that dipeptides and tripeptides can be absorbed intact from the gastrointestinal tract. However, the fate of larger peptides and small proteins remains unclear. Equally unclear are the biologic potencies of absorbed peptides and the quantity of peptide that must be administered into the gut to produce a biologic effect. Thus, the purpose of this study was to determine the effect of amino acid chain length on the ability of enterally administered peptides to produce biologic effects. Methods: Small bowel feeding tubes, jugular catheters, and arterial lines were placed into adult male Sprague-Dawley rats. Rats were administered intravenous (50 μg) and enteral (125 and 500 μg) thyrotropin-releasing hormone (TRH, a tripeptide), intravenous (100 μg) and enteral (100 and 500 μg) luteinizing hormone-releasing hormone (LHRH, a decapeptide), and intravenous (0.5 mg) and enteral (0.5 and 25 mg) insulin (a 51-amino acid polypeptide). The quantity of peptide administered represented less than 0.5% of a rat’s normal daily protein intake. The biologic effect of TRH, LHRH, and insulin were assessed using thyroid-stimulating hormone (TSH) response, follicle-stimulating hormone (FSH) response, and glucose. We also measured serum levels of insulin in the rats following enteral insulin administration. Results: The results indicate that enteral TRH (125 and 500 μg) produced the same TSH response as intravenous TRH. The response to 500 μg enteral LHRH was 50% of the response to intravenous LHRH and the response to 25 mg enteral insulin was 30% of the response to 0.5 mg intravenous insulin. Serum insulin levels increased significantly following both 0.5 and 25 mg enteral insulin. Conclusions: These results support the concept that small (di- and tripeptides) and large (10–51 amino acids) peptides generated in the diet can be absorbed intact through the intestines and produce biologic effects at the tissue level. The potency of the enterally administered peptides decreases as the chain length increases. We postulate that absorbed dietary peptides play a role in the modulation of organ function and disease progression.

Vasodilatory actions of the dietary peptide carnosine.

The objective of this study was to test the hypothesis that the dietary dipeptide carnosine (beta-alanine-L-histidine) causes direct decreases in arterial tone. Isolated descending thoracic aortic rings from male Sprague-Dawley rats were used for all studies. Preconstriction of vessels was accomplished with phenylephrine. Carnosine (0.625-20 mM) produced dose-dependent vascular relaxation (P < 0.05) that was independent of endothelium. The constituent amino acid L-histidine did not produce any significant relaxation over the same dose range, whereas beta-alanine actually produced dose-dependent vasoconstriction (P < 0.05). The soluble guanylate cyclase inhibitor methylene blue (10(-5) M) significantly decreased the relaxation produced by carnosine (P < 0.05). Measurement of cyclic GMP in the presence and absence of methylene blue after carnosine and phenylephrine exposure was also done. Methylene blue 10(-5) M resulted in a decrease in cyclic GMP levels from 65.3 +/- 15.6 fmol/mg protein to 8.6 +/- 0.9 fmol/mg of protein (P = 0.001). We conclude that carnosine produces relaxation of isolated rat aorta independent of endothelium. The effect of carnosine is at least in part mediated via cyclic GMP production and is not reproduced by its constituent amino acids, L-histidine and beta-alanine.

Enteral feeding minimizes liver injury during hemorrhagic shock.

Liver injury is common in patients following hemorrhage and sepsis. There are multiple etiologies for this liver injury which involve both decreased nutrient blood flow and direct cellular injury. Enteral nutrients vasodilate gut blood vessels and increase blood flow to the intestines and liver. Since enteral nutrients vasodilate gut blood vessels, we wondered whether luminal nutrition would prevent hepatic injury during shock states. We randomized Sprague-Dawley rats to saline or enteral nutrition via duodenal feeding tubes. Animals were then subjected to 60 min of hemorrhagic hypotension or intraperitoneal injection of lipopolysaccharide (LPS). Liver injury was assessed by measuring levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) before and after hemorrhage or LPS. Enteral nutrients significantly decreased liver injury following hemorrhage. AST increased from 246 +/- 17 to 1605 +/- 593 U/L in saline animals and 283 +/- 39 to 551 +/- 94 U/L in enterally fed animals. ALT increased from 60 +/- 4 to 726 +/- 355 U/L in saline animals and 61 +/- 6 to 161 +/- 38 U/L in enterally fed animals. Enteral nutrients did not significantly alter the increase in AST/ALT following LPS. These results indicate that enteral nutrients can decrease liver injury following hemorrhagic hypotension.

Dietary peptides improve wound healing following surgery

To determine if peptide-based enteral diets improve wound healing when compared to amino acid-based diets, a prospective randomized study was conducted using 38 male Sprague-Dawley rats. Following placement of a standardized abdominal wound, 20 animals were randomized to an isonitrogenous peptide-based (PEP) versus amino acid-based diet (AA) for 10 d. In addition, 18 animals were randomized to an amino acid-based diet supplemented with the peptide carnosine (CARN) or its constituent amino acids (Control). Diets were administered through small bowel feeding tubes. Wound bursting pressure was significantly higher in the PEP animals compared to the AA animals (179+/-9 versus 138+/-12 mmHg; P=0.02). In addition, wound bursting pressure was significantly greater in the CARN animals compared to the Control animals (143+/-10 versus 116+/-8 mmHg; P=0.005). Peptide-based enteral diets improve wound healing when compared to nonpeptide generating amino acid-based diets. We also conclude that the dietary peptide carnosine represents a dietary peptide that improves wound healing when administered as part of a complete enteral formula. This effect on wound healing may be clinically relevant because carnosine is not found in most enteral formulas.

Hand-held blood gas analyzer is accurate in the critical care setting.

OBJECTIVE To determine the accuracy of a new, portable battery-powered blood gas analyzer when used by nonlaboratory-trained clinicians in the critical care setting. DESIGN Prospective analysis of blood samples from critically ill patients. SETTING Large tertiary critical care unit. PATIENTS Heterogeneous group of medical and surgical critically ill patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Two hundred thirty-nine split blood samples from intensive care patients were analyzed by clinicians in the critical care environment using a new, portable, battery-powered blood gas analyzer (Immediate Response Mobile Analyzer [IRMA], Diametrics Medical, St. Paul, MN). Near-patient measurements were compared with measurements obtained by laboratory technologists using an IL-1312 blood gas analyzer (Instrumentation Laboratories, Lexington, MA) in an established near-patient critical care laboratory. Precision and coefficients of variation were also determined using repeated testing of quality control samples at three levels of pH, PO2, and PCO2. There was good agreement between IRMA determinations and the laboratory. Correlation coefficients ranged from 0.96 to 0.99. Bias and precision (+/-2 SD), respectively, were 0.02 and 0.036 units for pH, -0.3 torr (1.8 kPa) (-0.04 kPa) and 7.2 torr (0.96 kPa) for PCO2 and -3.9 torr (0.52 kPa) and 13.8 torr (1.8 kPa) for PO2. Precision on repeated testing of quality control samples ranged from 0.022 to 0.04 units for a pH of 7.2 to 7.6, 1.2 to 4.6 torr (0.16 to 0.61 kPa) for a PCO2 of 20 to 60 torr (2.7 to 8 kPa), and 3.0 to 7.4 torr (0.40 to 0.99 kPa) for a PO2 of 70 to 160 torr (9.3 to 21.3 kPa). Coefficients of variation ranged from 0.15% to 0.28% for a pH of 7.2 to 7.6, 2.0% to 3.7% for a PCO2 of 20 to 60 torr (2.7 to 8.0 kPa), and 1.7% to 3.6% for a PO2 of 70 to 160 torr (9.3 to 21.3 kPa). Mean turnaround time was 16.5 +/-10.1 mins for the near-patient laboratory and 2+/-0.5 mins for IRMA. CONCLUSIONS IRMA is accurate and reproducible when used in the clinical setting by nonlaboratory-trained individuals. Nonlaboratory-trained individuals can obtain laboratory results in the critical care setting comparable with the results obtained by trained laboratory technologists. Bedside laboratory testing decreases turnaround time compared with a near-patient laboratory.

Autonomic dysfunction secondary to intracerebral hemorrhage.

IMPLICATIONS We report a case of autonomic dysfunction secondary to intracranial hemorrhage. The patient had periodical episodes of hypertension, tachycardia, tachypnea, and diaphoresis that responded dramatically to Thorazine, but not to conventional measures.

Magnesium antagonizes the actions of lysophosphatidyl choline (LPC) in myocardial cells : a possible mechanism for its antiarrhythmic effects

Patients with cardiac arrhythmias, ischemia, and infarction may benefit from administration of supplemental magnesium.However, the exact mechanisms for magnesiums beneficial effects remain unknown. Lysophosphatidyl choline (LPC), an amphipathic phospholipid released from cardiac cell membranes during ischemia, increases free intracellular calcium concentrations ([Ca]i) and has been implicated as a cause of cardiac arrhythmias and coronary artery spasm during myocardial ischemia. We postulated that magnesium acts by inhibiting cellular calcium overload induced by mediators such as LPC. Myocardial cells from male Sprague-Dawley rats were isolated from ventricular tissue samples and [Ca]i determined using the fluorescent dye, fura-2/acetoxymethyl ester, measured in a spectrofluorometer. The increase in [Ca]i after exposure to 100 and 200 micro Meter LPC was recorded in cells suspended in modified Dulbeccos phosphate buffered saline solution with 0.2, 2.0, and 20 mM magnesium chloride. Differences were determined by analysis of variance with P < 0.05 considered significant. LPC significantly increased [Ca]i in the 100 micro Meter (506 +/- 76 nM) and 200 micro Meter (675 +/- 81 nM) concentrations, compared to baseline (301 +/- 25 nM). MgCl2 at both the 2.0 and 20 mM concentrations significantly blunted the increase in [Ca]i in myocardial cells exposed to LPC, whereas 0.2 mM MgCl2 was ineffective. LPC is a potent lipid mediator which increases myocyte [Ca]i in a concentration-dependent manner. Magnesium concentrations >or=to2.0 mM effectively antagonize the increase in [Ca]i induced by LPC. Thus, magnesium may limit intracellular calcium overload stimulated by ischemic-induced LPC release. (Anesth Analg 1995;80:1083-7)

Inhibition of nitric oxide synthase enhances the myocardial toxicity of phenylpropanolamine.

ObjectiveTo investigate the direct and indirect effects of the anorexic agent phenylpropanolamine (PPA) on the heart and to determine whether nitric oxide deficiency exacerbates the myocardial toxicity of PPA. DesignDose response effects using sequential drug administration. SettingAnimal research laboratory of a large tertiary academic medical center. SubjectsIsolated hearts (n = 8) from male Sprague-Dawley rats weighing 300–400 g. InterventionsMeasurement of heart rate, maximal change in pressure over time (dP/dtmax), −dP/dtmax, and coronary blood flow in isolated hearts perfused on a Langendorff apparatus. PPA was infused through the aortic cannula at 0.05, 0.125, 0.25, 0.5, and 1.25 mmol/L before and after inhibition of nitric oxide synthesis with N-nitro-l-arginine methyl ester (L-NAME). ResultsPPA had little effect on myocardial contractility of normal hearts until the highest dose of PPA (1.25 mmol/L). However, after L-NAME, PPA significantly depressed contractility at a dose of 0.25 mmol/L. PPA had no significant effects on coronary blood flow. PPA failed to induce arrhythmias in normal hearts. However, after L-NAME, PPA induced ventricular fibrillation in 50% of the hearts. ConclusionPPA causes myocardial contractile depression without altering global coronary artery blood flow. Inhibition of nitric oxide synthesis sensitizes the heart to the myocardial depressant effects of PPA and increases the risk for ventricular fibrillation.

Same-Patient Reproducibility of State Entropy: A Comparison of Simultaneous Bilateral Measurements During General Anesthesia

BACKGROUND: State Entropy® (SE) is an index of anesthetic depth similar to Bispectral Index® (BIS). Both indices use a single-channel electroencephalogram, recorded from a unilaterally applied electrode on the forehead, as their input. Intrapatient reproducibility of BIS was questioned in a recent study in which simultaneous measurements from two electrodes applied to the same patient showed conflicting anesthetic depths. Our purpose was to determine whether SE results are similarly reproducible, even though their computation uses a different algorithm than BIS. In this study, we investigated the reproducibility of SE measurements simultaneously obtained from bilaterally applied electrodes in the same patient. METHODS: Entropy electrodes were applied bilaterally on 21 patients under general inhaled anesthesia. Simultaneous SE measurements from both electrodes were recorded every 10 s from each patient. Data were analyzed with Bland-Altman statistics. RESULTS: We obtained 14,379 pairs of SE measurements. Four percent of the individual measurements suggested conflicting anesthetic depth along with a numeric difference more than 10 points. Bias was not clinically significant (−0.3). Ninety-five percent limits of agreement were −11.7 and +11.6. CONCLUSIONS: SE showed a clinically significant degree of disagreement when probes were applied on both sides of the forehead in the same patient. Bland-Altman statistics showed better same-patient reproducibility in SE than did a similar study on BIS. Nevertheless, 4% of the simultaneously measured pairs of SE suggested different anesthetic depths and differed by more than 10 points. Caution is advised when using SE as a clinical index of anesthetic depth.