bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Pulmonary Inflammation in Patients without Preexisting Lung Injury
Authors: Wolthuis Esther K. , Choi Goda , Dessing Mark C. , Bresser Paul , Lutter Rene , Dzoljic Misa , van der Poll Tom , Vroom Margreeth B. , Hollmann Markus , Schultz Marcus J. 
Published: March 2009

Background
Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury.

Methods
Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes.

Results
Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P < 0.01). Levels of tumor necrosis factor alpha, IL-1alpha, IL-1beta, IL-6, macrophage inflammatory protein 1alpha, and macrophage inflammatory protein 1beta in the bronchoalveolar lavage fluid were not affected by mechanical ventilation. Plasma levels of IL-6 and IL-8 increased with mechanical ventilation, but there were no differences between the two ventilation groups.

Conclusion
The use of lower tidal volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.
Are Blood Transfusions Associated with Greater Mortality Rates?
Authors: Vincent Jean-Louis , Sakr Yasser , Sprung Charles , Harboe Svein , Damas Pierre 
Published: March 2009

Background
Studies have suggested worse outcomes in transfused patients and improved outcomes in patients managed with restricted blood transfusion strategies. The authors investigated the relation of blood transfusion to mortality in European intensive care units (ICUs).

Methods
The Sepsis Occurrence in Acutely Ill Patients study was a multicenter, observational study that included all adult patients admitted to 198 European ICUs between May 1 and May 15, 2002 and followed them until death, until hospital discharge, or for 60 days. Patients were classified depending on whether they had received a blood transfusion at any time during their ICU stay.

Results
Of 3,147 patients, 1,040 (33.0%) received a blood transfusion. These patients were older (mean age, 62 vs. 60 yr; P = 0.035) and were more likely to have liver cirrhosis or hematologic cancer, to be a surgical admission, and to have sepsis. They had a longer duration of ICU stay (5.9 vs. 2.5 days; P < 0.001) and a higher ICU mortality rate (23.0 vs. 16.3%; P < 0.001) but were also more severely ill on admission (Simplified Acute Physiology Score II, 40.2 vs. 34.7; P < 0.001; Sequential Organ Failure Assessment score, 6.5 vs. 4.5; P < 0.001). There was a direct relation between the number of blood transfusions and the mortality rate, but in multivariate analysis, blood transfusion was not significantly associated with a worse mortality rate. Moreover, in 821 pairs matched according to a propensity score, there was a higher 30-day survival rate in the transfusion group than in the other patients (P = 0.004).

Conclusion
This observational study does not support the view that blood transfusions are associated with increased mortality rates in acutely ill patients.
Predictors of Cognitive Dysfunction after Major Noncardiac Surgery
Authors: Monk Terri G. , Weldon B Craig , Garvan Cyndi W. , Dede Duane E. , van der Aa Maria T. , Heilman Kenneth M. , Gravenstein Joachim S. 
Published: March 2009

Background
The authors designed a prospective longitudinal study to investigate the hypothesis that advancing age is a risk factor for postoperative cognitive dysfunction (POCD) after major noncardiac surgery and the impact of POCD on mortality in the first year after surgery.

Methods
One thousand sixty-four patients aged 18 yr or older completed neuropsychological tests before surgery, at hospital discharge, and 3 months after surgery. Patients were categorized as young (18-39 yr), middle-aged (40-59 yr), or elderly (60 yr or older). At 1 yr after surgery, patients were contacted to determine their survival status.

Results
At hospital discharge, POCD was present in 117 (36.6%) young, 112 (30.4%) middle-aged, and 138 (41.4%) elderly patients. There was a significant difference between all age groups and the age-matched control subjects (P < 0.001). At 3 months after surgery, POCD was present in 16 (5.7%) young, 19 (5.6%) middle-aged, and 39 (12.7%) elderly patients. At this time point, the prevalence of cognitive dysfunction was similar between age-matched controls and young and middle-aged patients but significantly higher in elderly patients compared to elderly control subjects (P < 0.001). The independent risk factors for POCD at 3 months after surgery were increasing age, lower educational level, a history of previous cerebral vascular accident with no residual impairment, and POCD at hospital discharge. Patients with POCD at hospital discharge were more likely to die in the first 3 months after surgery (P = 0.02). Likewise, patients who had POCD at both hospital discharge and 3 months after surgery were more likely to die in the first year after surgery (P = 0.02).

Conclusions
Cognitive dysfunction is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 yr or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery.
Persistent Depression of Contractility and Vasodilation with Propofol but Not with Sevoflurane or Desflurane in Rabbits
Authors: Royse Colin Forbes , Liew David F. L. , Wright Christine E. , Royse Alistair G. , Angus James A. 
Published: March 2009

Background
Propofol, sevoflurane, and desflurane may cause hemodynamic compromise during anesthesia and critical care management. The aim of the study was to compare these anesthetics during increased dose and recovery to maintenance level.

Methods
Anesthetized, open-chest New Zealand White rabbits were used to acquire dose-response curves with sevoflurane, desflurane, and propofol, followed by reduction to baseline infusion. Simultaneous high-fidelity left ventricular pressure and volume data were acquired during caval occlusion with a dual-field conductance catheter inserted via an apical stab. The preload recruitable stroke work and the end-diastolic pressure-volume relationship were used as the primary measures of contractility and diastolic function.

Results
The time-matched controls were stable over time. Propofol and desflurane but not sevoflurane caused dose-dependent reductions in myocardial contractility, although sevoflurane reduced contractility more at 1 minimal alveolar concentration. All anesthetics reduced mean arterial pressure, and significant recovery occurred for sevoflurane and desflurane but not for propofol. The end-diastolic pressure-volume relationship was increased by sevoflurane. Ejection fraction decreased with sevoflurane only. All anesthetics caused dose-dependent vasodilation, with recovery for desflurane and sevoflurane but not propofol. Heart rate was decreased with propofol without significant recovery. Propofol plasma concentrations remained elevated after dose return to baseline infusion rate, suggestive of distribution compartment saturation.

Conclusion
All three anesthetics caused dose-dependent decreases in cardiovascular function. Recovery of cardiovascular function occurred rapidly with sevoflurane and desflurane, but persistent depression of contractility, vasodilation, mean arterial pressure, and heart rate occurred with propofol during a 30-min recovery period.
Bispectral Index, Entropy, and Quantitative Electroencephalogram during Single-agent Xenon Anesthesia
Authors: Laitio Ruut M. , Kaskinoro Kimmo , Särkelä Mika O. K. , Kaisti Kaike K. , Salmi Elina , Maksimow Anu , Långsjö Jaakko W. , Aantaa Riku , Kangas Katja , Jääskeläinen Satu , Scheinin Harry 
Published: March 2009

Background
The aim was to evaluate the performance of anesthesia depth monitors, Bispectral Index (BIS) and Entropy, during single-agent xenon anesthesia in 17 healthy subjects.

Methods
After mask induction with xenon and intubation, anesthesia was continued with xenon only. BIS, State Entropy and Response Entropy, and electroencephalogram were monitored throughout induction, steady-state anesthesia, and emergence. The performance of BIS, State Entropy, and Response Entropy were evaluated with prediction probability, sensitivity, and specificity analyses. The power spectrum of the raw electroencephalogram signal was calculated.

Results
The mean (SD) xenon concentration during anesthesia was 66.4% (2.4%). BIS, State Entropy, and Response Entropy demonstrated low prediction probability values at loss of response (0.455, 0.656, and 0.619) but 1 min after that the values were high (0.804, 0.941, and 0.929). Thereafter, equally good performance was demonstrated for all indices. At emergence, the prediction probability values to distinguish between steady-state anesthesia and return of response for BIS, State Entropy, and Response Entropy were 0.988, 0.892, and 0.992. No statistical differences between the performances of the monitors were observed. Quantitative electroencephalogram analyses showed generalized increase in total power (P < 0.001), delta (P < 0.001) and theta activity (P < 0.001), and increased alpha activity (P = 0.003) in the frontal brain regions.

Conclusions
Electroencephalogram-derived depth of sedation indices BIS and Entropy showed a delay to detect loss of response during induction of xenon anesthesia. Both monitors performed well in distinguishing between conscious and unconscious states during steady-state anesthesia. Xenon-induced changes in electroencephalogram closely resemble those induced by propofol.
Effects of Aprotinin Dosage on Renal Function
Authors: Dietrich Wulf , Busley Raimund , Boulesteix Anne-Laure 
Published: March 2009

Background
The nonspecific serine protease inhibitor aprotinin is widely used in cardiac surgery to limit bleeding. Recently, concerns about the safety of this drug were raised, especially regarding impaired renal outcome. This event rate was supposed to be dose dependent.

Methods
In this observational study, the authors analyzed prospectively collected data of a single-center cardiac-anesthetic database. Adult patients treated with various dosages of aprotinin were evaluated. Logistic regression analysis identified independent predictors of renal outcome. The primary endpoint was a composite of novel postoperative renal failure requiring hemodialysis, an increased postoperative creatinine plasma concentration of 2 mg/dl or greater, or a difference between maximal postoperative and preoperative plasma creatinine of 0.7 mg/dl or greater.

Results
The study analyzed 8,548 patients. Multiple logistic regression (c index = 0.861) did not show a significant association between aprotinin dosage and renal outcome, as did the bootstrap procedure (odds ratio, 0.98; confidence interval, 0.90-1.07). The most relevant predictor was a preoperatively elevated creatinine concentration (odds ratio, 11.4; confidence interval, 9.05-14.3). Patients with postoperative renal impairment or failure were at higher preoperative risk and/or underwent more complex procedures. In subgroups of patients with preoperatively impaired renal function (creatinine > or =1.5 mg/dl) (n = 1,075), complex procedures (n = 1,920), or insulin-dependent diabetes (n = 650) or patients undergoing isolated myocardial revascularization (n = 4,901), no association between aprotinin dosage and adverse renal outcome was observed.

Conclusion
In the current analysis, aprotinin dosage was not associated with increased adverse renal outcome. In regard to renal outcome, this analysis did not demonstrate an essential detrimental influence of aprotinin dosage on renal function.
Desflurane but Not Sevoflurane Impairs Airway and Respiratory Tissue Mechanics in Children with Susceptible Airways
Authors: von Ungern-Sternberg Britta S. , Saudan Sonja , Petak Ferenc , Hantos Zoltan , Habre Walid 
Published: March 2009

Background
Although sevoflurane and desflurane exert bronchoactive effects, their impact on the airway and respiratory tissue mechanics have not been systematically compared in children, especially in those with airway susceptibility (AS). The aim of this study was to assess airway and respiratory tissue mechanics in children with and without AS during sevoflurane and desflurane anesthesia.

Methods
Respiratory system impedance was measured in healthy control children (group C, n = 20) and in those with AS (group AS, n = 20). Respiratory system impedance was determined during propofol anesthesia and during inhalation of sevoflurane and desflurane 1 minimum alveolar concentration in random order. Airway resistance, tissue damping, and elastance were determined from the respiratory system impedance spectra by model fitting.

Results
Children in group AS exhibited significantly higher respiratory impedance parameters compared with those in group C. Sevoflurane slightly decreased airway resistance (-7.0 +/- 1.5% vs. -4.8 +/- 2.4% in groups C and AS, respectively) in both groups. In contrast, desflurane caused elevations in airway resistance and tissue mechanical parameters, with markedly enhanced airway narrowing in children with AS (18.2 +/- 2.8% vs. 53.9 +/- 5%; P < 0.001 for airway resistance in groups C and AS, respectively). Neither the order of drug administration nor the time after the establishment of their steady state concentrations affected these findings.

Conclusions
These results emphasized the deleterious effects of desflurane on the airways, particularly in children with susceptible airways in contrast with the consistent beneficial effects of sevoflurane, questioning the use of desflurane in children with AS.
Identification and Biochemical Characterization of a Novel Ryanodine Receptor Gene Mutation Associated with Malignant Hyperthermia
Authors: Anderson Ayuk A. , Brown Rosemary L. , Polster Brenda , Pollock Neil , Stowell Kathryn M. 
Published: March 2009

Background
Mutations in the skeletal muscle ryanodine receptor gene may result in altered calcium release from sarcoplasmic reticulum stores, giving rise to malignant hyperthermia (MH). MH is a pharmacogenetic skeletal muscle disorder triggered by volatile anesthetics and depolarizing muscle relaxants. Diagnosis of MH is by in vitro contracture testing of quadriceps muscle. DNA analysis of causative mutations is limited by the large number of mutations that cosegregate with MH and the relatively few that have been biochemically characterized.

Methods
DNA sequence analysis was used to screen the skeletal muscle ryanodine receptor gene in MH-susceptible individuals. A diagnostic test using real-time polymerase chain reaction was developed to detect the mutation in individuals diagnosed as MH susceptible by in vitro contracture testing. The functional relevance of this mutation was examined in Epstein-Barr virus-immortalized B-lymphoblastoid cells.

Results
A novel ryanodine receptor mutation (cytosine 14997 thymine resulting in a histidine 4833 tyrosine substitution) was identified in pathology specimens from two patients with fatal MH reactions. B lymphocytes from patients with this mutation were approximately twofold more sensitive than MH-negative cells to activation with 4-chloro-m-cresol. The amount of Ca released from B lymphocytes of MH-susceptible patients was significantly greater than that released from cells of family members without this mutation. Haplotype analysis suggests that both families had a common ancestor.

Conclusions
DNA analysis to detect mutations which cosegregate with MH as well as biochemical assays on cultured lymphocytes obtained from blood can serve as useful diagnostic tools for MH susceptibility and genotype-phenotype correlations.
Inhibition of Poly(Adenosine Diphosphate–Ribose) Polymerase Attenuates Ventilator-induced Lung Injury
Authors: Vaschetto Rosanna , Kuiper Jan W. , Chiang Shyh Ren , Haitsma Jack J. , Juco Jonathan W. , Uhlig Stefan , Plötz Frans B. , Corte Francesco Della , Zhang Haibo , Slutsky Arthur S. 
Published: March 2009

Background
Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury.

Methods
Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34.

Results
The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney.

Conclusion
The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.
Enhanced Peripheral Analgesia Using Virally Mediated Gene Transfer of the μ-Opioid Receptor in Mice
Authors: Zhang Guohua , Mohammad Husam , Peper Brad D. , Raja Srinivasa , Wilson Steven P. , Sweitzer Sarah M. 
Published: March 2009

Background
The use of opioids to treat pain is often limited by side effects mediated through the central nervous system. The current study used a recombinant herpes simplex virus type 1 to increase expression of the mu-opioid receptor (muOR) in primary afferent neurons. The goal of this strategy was to enhance peripheral opioid analgesia.

Methods
Cutaneous inoculation with herpes simplex virus containing muOR complementary DNA (cDNA) in antisense (SGAMOR) or sense (SGMOR) orientation relative to a constitutive promoter, or complementary DNA for Escherichia coli lac Z gene as a control virus (SGZ) was used to modify the levels of muOR in primary afferents. The effects of altered muOR levels on peripheral analgesia were then examined.

Results
At 4 weeks after SGAMOR and SGMOR infection, decreased and increased muOR immunoreactivity was observed in ipsilateral dorsal hind paw skin, lumbar dorsal root ganglion cells, and superficial dorsal horns, respectively, compared with SGZ. This change in muOR expression in mice by SGAMOR and SGMOR was accompanied at the behavioral level with a rightward and leftward shift in the loperamide dose-response curve, respectively, compared with SGZ.

Conclusions
This gene therapy approach may provide an innovative strategy to enhance peripheral opioid analgesia for the treatment of pain in humans, thereby minimizing centrally mediated opioid side effects such as sedation and addiction.
Attenuation of the 40-Hertz Auditory Steady State Response by Propofol Involves the Cortical and Subcortical Generators
Authors: Plourde Gilles , Garcia-Asensi Alfonso , Backman Steven , Deschamps Alain , Chartrand Daniel , Fiset Pierre , Picton Terence W. 
Published: March 2009

Background
The 40-Hz auditory steady state response (40-Hz ASSR) provides a reliable marker of anesthetic-induced unconsciousness. Brain electric source analysis indicates that the 40-Hz ASSR arises from cortical and subcortical generators. The authors used source analysis to assess the effect of propofol anesthesia on the cerebral generators of the 40-Hz ASSR. They also examined the effect of propofol on two auditory evoked potentials of cortical origin: the N1 and the sustained potential.

Methods
Eleven healthy human volunteers were anesthetized with propofol given in target-concentration mode at the minimal concentration causing unconsciousness. The 40-Hz ASSR was recorded before, during, and after anesthesia. The source model consisted of five concurrently active generator dipoles: two in the contralateral auditory cortex (one tangentially oriented, one radially oriented), two in the ipsilateral auditory cortex (same orientations), and one in the midline brainstem.

Results
During anesthesia, the strength of the cortical and brainstem dipoles was reduced to the same extent (to 54% of baseline for the four cortical dipoles pooled vs. 53% for the brainstem dipole). Dipole strength during anesthesia was significantly less (P < 0.01) than during baseline and recovery for both cortical and brainstem dipoles. The N1 and sustained potential were no longer recordable during anesthesia.

Conclusions
The attenuation of the 40-Hz ASSR during propofol anesthesia results from a reduction of similar magnitude of the activity of the cortical and brainstem generators. The N1 and sustained potential are so profoundly attenuated during propofol anesthesia that they are no longer recordable from the scalp.
The Neonatologist's Dilemma: Catch‐up Growth or Beneficial Undernutrition in Very Low Birth Weight Infants—What Are Optimal Growth Rates?
Authors: Thureen Patti J 
Published: March 2009

ABSTRACTAs the threshold of viability decreases, clinicians who care for preterm neonates increasingly are faced with making decisions regarding feeding in a population for which there are no clear guidelines and minimal scientific data to inform optimal nutritional strategies. It is becoming more apparent that the amount of nutrition, as well as the timing of nutrient delivery, may affect long‐term growth and metabolic outcomes. Both overnutrition and undernutrition at critical growth periods may have adverse effects. The risks and benefits of nutrient delivery designed to achieve “catch‐up” growth need to be further identified. This article reviews both established concepts and more recently identified issues that need to be considered by the neonatologist when making feeding decisions in the very preterm neonate.