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Biomedical subjects

K Hawkins

Publications and source records attributed to K Hawkins.

At least 19 recordsLinked to original sources
PubMed2006

Commercial sex venues: a closer look at their impact on the syphilis and HIV epidemics among men who have sex with men.

OBJECTIVE: To provide insight into the role of commercial sex venues in the spread of syphilis and HIV among men who have sex with men (MSM). STUDY: A cross sectional study of 1351 MSM who were diagnosed with early syphilis who did and did not encounter sexual partners at commercial sex venues. RESULTS: Overall, 26% MSM diagnosed with syphilis had sexual encounters at commercial sex venues. Of these, 74% were HIV positive, 94% reported anonymous sex, and 66% did not use a condom. Compared to those who did not have a sexual encounter at these venues, they were twice as likely to be HIV positive (OR = 1.91, 95% CI 1.36 to 2.68), six times more likely to have anonymous sex (OR = 6.18, 95% CI 3.37 to 11.32), twice as likely not to use condom (OR = 2.02, 95% CI 1.71 to 2.38), and twice as likely to use non-injecting drugs (OR = 1.65, 95% CI 1.21 to 2.37). CONCLUSIONS: MSM diagnosed with syphilis who frequent commercial sex venues are engaging in high risk behaviours for syphilis and HIV transmission and acquisition. Thus commercial sex venues are one of the focal points of syphilis and HIV transmission and acquisition.

Adult↗
PubMed2006

The Bradford bone-anchored hearing aid programme: impact of the multidisciplinary team.

OBJECTIVES: The aim of this study was to assess the impact on implant survival, abutment skin reaction and patient satisfaction in patients implanted with a bone-anchored hearing aid (BAHA), following the introduction of a multidisciplinary team (MDT) in 1997. DESIGN AND METHODS: Part prospective and retrospective analysis. Implant survival and cause of failures were recorded along with abutment skin reaction (graded as none, mild, moderate and severe, according to the amount of wound care required). Patient satisfaction and quality of life were assessed using a questionnaire enquiring about several aspects of the use and benefits of their BAHA. SETTING AND PARTICIPANTS: Eighty patients treated at the Bradford Royal Infirmary between 1991 and 2005. The unit is a recognized tertiary referral centre. RESULTS AND CONCLUSIONS: Twelve out of 80 implants failed, giving an overall failure rate of 15 per cent. Kaplan-Meier survival curves show a steady decrease in implant survival. The MDT had a positive effect on implant survival and adverse skin reactions, with a higher proportion of patients experiencing no reaction after its introduction. There was a 92.5 per cent response rate to the questionnaire. Overall patient satisfaction was high, both before and after the introduction of the MDT.

Adolescent↗
PubMed2006

Pressure relieving support surfaces: a randomised evaluation.

OBJECTIVES: To determine differences between alternating pressure overlays and alternating pressure replacement mattresses with respect to the development of new pressure ulcers, healing of existing pressure ulcers, patient acceptability and cost-effectiveness of the different pressure-relieving surfaces. Also to investigate the specific additional impact of pressure ulcers on patients' well-being. DESIGN: A multicentre, randomised, controlled, open, fixed sample, parallel-group trial with equal randomisation was undertaken. The trial used remote, concealed allocation and intention-to-treat (ITT) analysis. The main trial design was supplemented with a qualitative study involving a purposive sample of 20-30 patients who developed pressure ulcers, to assess the impact of the pressure ulcers on their well-being. In addition, a focus group interview was carried out with clinical research nurses, who participated in the PRESSURE (Pressure RElieving Support SUrfaces: a Randomised Evaluation) Trial, to explore the experiences of their role and observations of pressure area care. SETTING: The study took place in 11 hospital-based research centres within six NHS trusts in England. PARTICIPANTS: Acute and elective patients aged 55 years or older and admitted to vascular, orthopaedic, medical or care of the elderly wards in the previous 24 hours were investigated. INTERVENTIONS: Patients were randomised to either an alternating pressure overlay or an alternating pressure mattress replacement, with mattress specifications clearly defined to enable the inclusion of centres using products from different manufacturers, and to exclude hybrid mattress systems (which either combine foam or constant low pressure with alternating pressure in one mattress, or can be used as either an overlay or a replacement mattress). MAIN OUTCOME MEASURES: Development of a new pressure ulcer (grade < or =2, i.e. partial-thickness wound involving epidermis/dermis only) on any skin site. Also healing of existing pressures ulcers, patient acceptability and cost-effectiveness. RESULTS: In total, 6155 patients were assessed for eligibility to the trial and 1972 were randomised: 990 to the alternating pressure overlay (989 after one postrandomisation exclusion) and 982 to the alternating pressure mattress replacement. ITT analysis found no statistically significant difference in the proportions of patients developing a new pressure ulcer of grade 2 or above [10.7% overlay patients, 10.3% mattress replacement patients, a difference of 0.4%, 95% confidence interval (CI) -2.3 to 3.1%, p = 0.75]. When logistic regression analysis was used to adjust for minimisation factors and prespecified baseline covariates, there was no difference between the mattresses with respect to the odds of ulceration (odds ratio 0.94, 95% CI 0.68 to 1.29). There was no evidence of a difference between the mattress groups with respect to time to healing (p = 0.86). The Kaplan-Meier estimate of the median time to healing was 20 days for each intervention. More patients allocated overlays requested mattress changes due to dissatisfaction (23.3%) than mattress replacement patients (18.9%, p = 0.02) and more than one-third of patients reporting difficulties associated with movement in bed and getting into or out of bed. There is a higher probability (64%) that alternating mattress replacements are cost-saving; they were associated with lower overall costs (74.50 pounds sterling per patient on average, mainly due to reduced length of stay) and greater benefits (a delay in time to ulceration of 10.64 days on average). Patients' accounts highlighted that the development of a pressure ulcer could be pivotal in the trajectory from illness to recovery, by preventing full recovery or causing varied impacts on their quality of life. CONCLUSIONS: There is no difference between alternating pressure mattress replacements and overlays in terms of the proportion of patients developing new pressure ulcers; however, alternating pressure mattress replacements are more likely to be cost-saving. The results suggest that when renewing alternating pressure surfaces or ordering equipment within a rental contract, mattress replacements should be specified; however, overlays are acceptable if no replacement mattress is available. Similarly, patient preferences can be supported, without any great increase in risk, if individual patients request an overlay rather than a replacement mattress. Further research could include a randomised controlled trial comparing alternating pressure mattress replacements and high-specification foam mattresses in patients at moderate to high risk; an accurate costing study to understand better how much pressure ulcers cost health and social services in the UK; and trials in higher risk groups of patients. Also future trials should measure time to ulceration as the primary end-point, since this is more informative economically and possibly also from a patient and clinical perspective.

Bedding and Linens↗
PubMed2006

Rheometrical and computational studies of blood viscoelasticity during coagulation.

The rheological behaviour of coagulating human blood has been measured using multiple strain wave frequencies. The results indicate that coagulating blood, prior to the point of incipient clot formation, can be modelled by a modified form of the Gross-Marvin 'ladder' model, and the benefits of such modeling for blood coagulation are discussed.

Blood Coagulation↗
PubMed2005

A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer.

AIMS: Whole-breast radiotherapy (WBRT) after conservative surgery for early breast cancer is a routine standard of care. Despite this, a number of uncertainties in management still exist. Over recent years, a number of new technologies have allowed the development of partial-breast irradiation, with the intention of improving the risk-benefit relationship of routine breast radiotherapy. We report the results of a trial comparing partial- with WBRT, with prolonged follow-up. MATERIALS AND METHODS: Between 1986 and 1990, 174 women were randomised to receive conventional whole-breast radiotherapy (WBRT) (40 Gy in 15 fractions), with a tumour-bed boost or partial-breast irradiation by a variety of techniques. Recruitment was problematic, and the trial closed prematurely well before meeting its recruitment target. RESULTS: A trend was observed towards higher local recurrence and a higher locoregional recurrence rate after irradiation of the tumour bed alone. Distant recurrence and survival were the same. CONCLUSIONS: Conclusions are limited in view of the failure to complete accrual of the target of 400 participants, and in the context of the techniques of partial-breast radiotherapy used during this study, which would not compare with those in current use. Tumour-bed irradiation alone cannot currently be recommended as routine treatment outside the context of clinical trial.

Adult↗
PubMed2004

Transforming growth factor-beta (TGF-beta) protein levels are not elevated in the blood or bile of patients with primary sclerosing cholangitis: a pilot study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder of unknown etiology characterized by progressive fibrosis and stricturing of the biliary tract. Transforming growth factor-beta (TGF-beta) is a family of cytokines produced by biliary tract epithelial cells that promote fibrinogenesis. Our objective was to determine whether TGF-beta levels are increased in the blood and/or bile of PSC patients compared to patients with other causes of obstructed biliary tracts (controls). Serum and bile TGF-beta levels were documented by enzyme-linked immunoassay in 10 adult PSC and 10 control patients obtained at the time of endoscopic retrograde cholangiography. Serum and bile TGF-beta levels were similar in the two groups (PSC versus control sera, 33.4 +/- 4.3 versus 27.5 +/- 7.7 ng/ml, and bile, 367 +/- 275 versus 457 +/- 247 ng/mg, respectively). Serum and bile TGF-beta levels are not increased in patients with PSC. Hence, the results of this pilot study do not support the hypotheses that PSC is caused by dysregulated TGF-beta expression.

Alkaline Phosphatase↗
PubMed2004

Agreement between preoperative core needle biopsy and postoperative invasive breast cancer histopathology is not dependent on the amount of clinical material obtained.

AIMS: To establish the relation between the amount of breast core needle biopsy (CNB) material examined and agreement between preoperative and postoperative histopathology parameters in invasive breast cancer. METHODS: The CNB and surgical specimen histopathology reports of 113 patients with invasive breast carcinoma were reviewed and the total amount of CNB material examined for each case was determined. Agreement was calculated for tumour type, grade, mitoses, nuclear pleomorphism, and tubule formation. Associations between the amount of CNB material and histopathology agreement before and after surgery were explored using binary logistic regression. RESULTS: Tumour type and grade agreed in 65.4% and 61.6% of cases, respectively. The components used to calculate grade--nuclear pleomorphism (57.4%), mitoses (59.4%), and tubule formation (55.6%)--agreed slightly less frequently. The proportion of cases with preoperative and postoperative assessments that agreed did not depend on the number of cores collected or the total amount of material examined. CONCLUSION: Neither tumour type and grade, nor the individual components used to calculate grade agreed consistently between the CNB and surgical specimen. The number of cores collected and the total amount of material reviewed by the pathologist does not influence the likelihood of agreement between preoperative and postoperative histopathology reports.

Biopsy, Needle↗
PubMed2002

Utility of zanamivir for chemoprophylaxis of concomitant influenza A and B in a complex continuing care population.

OBJECTIVE: To describe compliance with and the safety and prophylactic efficacy of zanamivir among patients at risk of developing influenza-related complications after exposure to both influenza A and B viruses. DESIGN: Nonrandomized trial using both historical and contemporaneous controls from ward populations within the same facility. SETTING: A 547-bed urban hospital providing complex continuing care and rehabiltation. PATIENTS: Fifty patients on a single ward concomitantly exposed to both influenza A and B during an influenza outbreak. INTERVENTIONS: All patients were screened for symptoms of influenza and nasopharyngeal swabs were sent for viral culture prior to treatment (two oral inhalations [2 x 5 mg] twice daily for 5 days) or prophylaxis (two oral inhalations [2 x 5 mg] once daily for 14 days) with zanamivir. Patient symptoms, compliance, and drug tolerance were monitored daily. Demographic data, comorbidities, vaccination status, and functional status (Katz score) were collected for all patients. RESULTS: The mean age of the patients was 70.6 years (standard deviation, +/- 16.4 years). Ninety-four percent had two or more comorbidities, 71% were dependent in two or more activities of daily living, 63% had been vaccinated for influenza, and 82% had received amantadine. Zanamivir was well tolerated, with 93% of the patients completing their course. The efficacy for preventing symptomatic infection was 82% and 91% (95% confidence interval, 62% to 98%) based on historical and contemporaneous controls, respectively. CONCLUSION: These data suggest that zanamivir can be used safely and effectively as a prophylactic agent in the management of influenza outbreaks in a complex continuing care population with multiple comorbidities.

Aged↗
PubMed2002

Use of fluoroquinolones in patients with chronic hepatitis C virus-induced liver failure.

Fluroquinolone antibiotics have been reported to have antiviral properties against RNA viruses, including hepatitis C virus (HCV). In the present study, five patients with advanced liver disease secondary to chronic HCV received 500 mg daily of oral ciprofloxacin for 30 days. Serum HCV-RNA levels and liver enzyme abnormalities remained largely unchanged. Thus, the role of fluoroquinolones as antiviral agents for chronic HCV in patients with advanced liver disease appears to be limited.

Alanine Transaminase↗
PubMed2001

Phosphorylation of Ser(982) in the sodium bicarbonate cotransporter kNBC1 shifts the HCO(3)(-) : Na(+) stoichiometry from 3 : 1 to 2 : 1 in murine proximal tubule cells.

1. Adenosine 3',5'-cyclic monophosphate (cAMP) modulates proximal tubule sodium and bicarbonate absorption by decreasing the rate of apical Na(+)-H(+) exchange and basolateral sodium bicarbonate efflux, through activation of protein kinase A (PKA). The electrogenic sodium bicarbonate cotransporter kNBC1 mediates basolateral sodium and bicarbonate efflux in the proximal tubule by coupling the transport of 1 Na(+) cation to that of 3 HCO(3)(-) anions. In this work we studied the effects of cAMP on the function of kNBC1 expressed heterologously in a proximal tubule cell line. 2. A mouse renal proximal tubule cell line, deficient in electrogenic sodium bicarbonate cotransport function, was transfected with kNBC1. Cells were grown on a permeable support to confluence, mounted in an Ussing chamber and permeabilized apically with amphotericin B. Current through the cotransporter was isolated as the difference current due to the reversible inhibitor dinitrostilbene disulfonate. The HCO(3)(-) : Na(+) stoichiometry of kNBC1 was calculated from its reversal potential by measuring the current-voltage relationships of the cotransporter at different Na(+) concentration gradients. 3. Addition of the potent cAMP agonist 8-Br-cAMP caused the stoichiometry of kNBC1 to shift from 3 HCO(3)(-) : 1 Na(+) to 2 HCO(3)(-) : 1 Na(+). Pretreatment of the cells with the PKA inhibitor H-89 abolished the effect of the agonist on the stoichiometry change. Replacing Ser(982) at the C-terminus consensus PKA phosphorylation site with alanine resulted in a failure of PKA to phosphorylate the transporter and induce a stoichiometry shift. 4. Our data indicate that cAMP modulates the stoichiometry of kNBC1 through activation of PKA. The change in stoichiometry from 3 : 1 to 2 : 1 is predicted to cause a shift in the direction of basolateral membrane sodium bicarbonate transport from efflux to influx. Ser(982) in the C-terminus of kNBC1 is a target for PKA phosphorylation. This is the first example of modulation of the stoichiometry of a membrane transporter by phosphorylation.

Amino Acid Sequence↗
PubMed2001

Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors.

This study details the profile of 13 cell surface cluster differentiation markers on human reserve stem cells derived from connective tissues. Stem cells were isolated from the connective tissues of dermis and skeletal muscle derived from fetal, mature, and geriatric humans. An insulin/dexamethasone phenotypic bioassay was used to determine the identity of the stem cells from each population. All populations contained lineage-committed myogenic, adipogenic, chondrogenic, and osteogenic progenitor stem cells as well as lineage-uncommitted pluripotent stem cells capable of forming muscle, adipocytes, cartilage, bone, fibroblasts, and endothelial cells. Flow cytometric analysis of adult stem cell populations revealed positive staining for CD34 and CD90 and negative staining for CD3, CD4, CD8, CD11c, CD33, CD36, CD38, CD45, CD117, Glycophorin-A, and HLA DR-II.

Aged↗
PubMed2001

The molecular basis of an avian plumage polymorphism in the wild: a melanocortin-1-receptor point mutation is perfectly associated with the melanic plumage morph of the bananaquit, Coereba flaveola.

BACKGROUND: Evolution depends on natural selection acting on phenotypic variation, but the genes responsible for phenotypic variation in natural populations of vertebrates are rarely known. The molecular genetic basis for plumage color variation has not been described in any wild bird. Bananaquits (Coereba flaveola) are small passerine birds that occur as two main plumage variants, a widespread yellow morph with dark back and yellow breast and a virtually all black melanic morph. A candidate gene for this color difference is the melanocortin-1 receptor (MC1R), a key regulator of melanin synthesis in feather melanocytes. RESULTS: We sequenced the MC1R gene from four Caribbean populations of the bananaquit; two populations of the yellow morph and two populations containing both the yellow morph and the melanic morph. A point mutation resulting in the replacement of glutamate with lysine was present in at least one allele of the MC1R gene in all melanic birds and was absent in all yellow morph birds. This substitution probably causes the color variation, as the same substitution is responsible for melanism in domestic chickens and mice. The evolutionary relationships among the MC1R haplotypes show that the melanic alleles on Grenada and St. Vincent had a single origin. The low prevalence of nonsynonymous substitutions among yellow haplotypes suggests that they have been under stabilizing selection, whereas strong selective constraint on melanic haplotypes is absent. CONCLUSIONS: We conclude that a mutation in the MC1R is responsible for the plumage polymorphism in a wild bird population and that the melanic MC1R alleles in Grenada and St. Vincent bananaquit populations have a single evolutionary origin from a yellow allele.

Animals↗
PubMed2001

The stoichiometry of the electrogenic sodium bicarbonate cotransporter NBC1 is cell-type dependent.

1. The pancreatic variant of the sodium bicarbonate cotransporter, pNBC1, mediates basolateral bicarbonate influx in the exocrine pancreas by coupling the transport of bicarbonate to that of sodium, with a 2 HCO3-:1 Na+ stoichiometry. The kidney variant, kNBC1, mediates basolateral bicarbonate efflux in the proximal tubule by coupling the transport of 3 HCO3- to 1 Na+. The molecular basis underlying the different stoichiometries is not known. 2. pNBC1 and kNBC1 are 93 % identical to each other with 41 N-terminal amino acids of kNBC1 replaced by 85 distinct amino acids in pNBC1. In this study we tested the hypothesis that the differences in stoichiometry are related to the difference between the N-termini of the two proteins. 3. Mouse renal proximal tubule and collecting duct cells, deficient in both pNBC1- and kNBC1-mediated electrogenic sodium bicarbonate cotransport function were transfected with either pNBC1 or kNBC1. Cells were grown on a permeable support to confluence, mounted in an Ussing chamber and permeabilized apically with amphotericin B. Current through the cotransporter was isolated as the difference current due to the reversible inhibitor dinitrostilbene disulfonate. The stoichiometry was calculated from the reversal potential by measuring the current-voltage relationships of the cotransporter at different Na+ concentration gradients. 4. Our data indicate that both kNBC1 and pNBC1 can exhibit either a 2:1 or 3:1 stoichiometry depending on the cell type in which each is expressed. In proximal tubule cells, both pNBC1 and kNBC1 exhibit a 3 HCO3-:1 Na+ stoichiometry, whereas in collecting duct cells, they have a 2:1 stoichiometry. These data argue against the hypothesis that the stoichiometric differences are related to the difference between the N-termini of the two proteins. Moreover, the results suggest that as yet unidentified cellular factor(s) may modify the stoichiometry of these cotransporters.

Animals↗
PubMed2001

Indicators of fatigue and of prolonged weaning from mechanical ventilation in surgical patients.

Indicators of weaning success have been tested primarily in patients who have been ventilated for short periods of time, and they may not be as accurate in cases where support has been required for longer than a few days. In patients requiring longer periods of support it is difficult to estimate the likelihood of successful liberation. Therefore we evaluated established weaning indices for their accuracy in surgical patients who required > or = 72 hours of mechanical ventilation. Surgical patients who required mechanical ventilation for > or = 72 hours were prospectively followed (over 6 months). We obtained standard indices of ventilatory function daily once patients were ready to wean. These indices included the respiratory rate/tidal volume ratio (RSBI), the maximal inspiratory pressure, and the minute ventilation. The duration of weaning and explicitly defined episodes of fatigue were the outcomes of interest. Statistical analyses evaluated the multiple factors that might influence the duration of weaning. Ninety-five patients (66% trauma; 34% surgery) survived to begin weaning, and 93% were liberated. The median duration of mechanical ventilation prior to weaning was 4 days (range 3-16 days), and the median duration of weaning was 3 days (range 0-56 days). Fatigue occurred in 36 patients and was not reliably predicted by any of the weaning measurements. However, a RSBI of > 105 on the first day of weaning was associated with prolonged weaning. By multivariate analysis, an RSBI of > 105 on the first day of weaning predicted prolonged weaning (hazard ratio 1.9; p = 0.03). After 72 hours of mechanical ventilation, clinical fatigue and successful liberation are not reliably predicted by standard indices of respiratory muscle strength and reserve. However, an RSBI of >105 observed once the patient is ready to wean is associated with prolonged weaning.

Adult↗
PubMed2001

Gastrointestinal complications in lung transplant survivors that require surgical intervention.

BACKGROUND: Lung transplantation is widely accepted as a treatment for end-stage lung disease. At present, information regarding the incidence and outcome of acute gastrointestinal complications in lung transplant survivors is limited. METHODS: Since 1990, 127 lung transplantations have been performed in 125 patients: 73 males (58 per cent) and 52 females (42 per cent) of median age 43 (range 9-64) years. Patients received a standard induction and maintenance regimen of immunosuppression. RESULTS: At a median follow-up of 2.6 (range 0-8.6) years the overall survival rate was 68 per cent. An acute abdomen requiring surgical intervention was diagnosed in 12 patients (10 per cent). The median time following lung transplantation was 19 (range 3-68) months. Eight cases of bowel perforation, two of appendicitis, one of colitis, one of cholecystitis, and one pneumoperitoneum were encountered. Four Hartmann procedures, two sigmoid resections, one small bowel resection, two appendicectomies, a subtotal colectomy, a cholecystectomy and an exploratory laparotomy were performed with minimal morbidity and no postoperative death. CONCLUSION: Lung transplant survivors are at increased risk of developing an acute abdomen because of the use of high-dose immunosuppressive agents. Physicians who evaluate lung transplant patients for an acute abdomen should have a low threshold for surgical intervention.

Abdomen, Acute↗
PubMed2001

An emergency department-based randomized trial of nonbronchoscopic bronchoalveolar lavage for early pathogen identification in severe community-acquired pneumonia.

STUDY OBJECTIVES: Many patients with community-acquired pneumonia are treated empirically without an aggressive search for causative pathogens, an approach adopted largely because of the costs and difficulties encountered during efforts to identify the causative organisms. Blood and sputum cultures are not sensitive, and the more invasive techniques of bronchoscopy and lung biopsy are generally time consuming and not cost-effective. The technique of nonbronchoscopic bronchoalveolar lavage (BAL) has been shown to accurately diagnose the causes of nosocomial pneumonia. The purpose of this study was to determine whether an emergency department-based BAL protocol would lead to more frequent isolation of pneumonia pathogens and result in more changes to tailored antibiotic therapy in comparison with standard care. METHODS: We studied all adult patients admitted with a diagnosis of pneumonia who were tracheally intubated and who had obtainable familial consent in the ED of an urban county hospital from March 1998 to October 1999. Exclusions included antibiotic use within the past 5 days, pneumothorax, hemoptysis, or persistent hypoxia using 100% oxygen. Patients were randomized to standard care versus standard care plus BAL. Blood culture specimens were drawn from all patients before the initiation of antibiotics. All other diagnostic tests were ordered at the discretion of treating physicians. BAL fluid, sputum, and blood culture specimens were tracked, and patient antibiotic course was followed to assess any change in regimen. RESULTS: Twenty-six of 64 patients evaluated for study participation met all eligibility criteria; 14 patients received standard care, and 12 patients received standard care plus BAL. Pneumonia pathogens were identified in 10 (83.3%) of 12 patients in the BAL group and in 4 (28.6%) of 14 patients in the standard care group (P =.007). Comparing BAL versus non-BAL groups, there was no significant difference in the likelihood of overall antibiotic regimen changes (P =.149), but there was a difference with regard to antibiotic changes made in patients with positive culture test results (P =.026). No major complications occurred with BAL catheterizations. CONCLUSION: ED-based BAL catheterization allows for early identification of pathogens in severe community-acquired pneumonia, which leads to changes in antibiotic therapy.

Adult↗
PubMed2001

Immediate effects of positive end-expiratory pressure and low and high tidal volume ventilation upon gas exchange and compliance in patients with acute lung injury.

BACKGROUND: Protective ventilation, in general, includes low tidal volume ventilation and maintaining end-inspiratory plateau pressures less than 35 cmH2O. Recent clinical studies have determined that such an approach results in improved survival in patients with moderate to severe acute lung injury and acute respiratory distress syndrome. However, experimental evidence suggests that repeated end-expiratory collapse and reexpansion contributes to ventilator-induced lung injury. We sought to determine the immediate effects of specific tidal volume-PEEP combinations upon oxygenation and static compliance in patients with moderate to severe acute lung injury. METHODS: Fourteen patients were prospectively studied and were treated with each of 10 tidal volume-PEEP combinations, applied in random order. After 5 minutes at each tidal volume-PEEP combination, PaO2/FIO2 and static compliance were recorded. Comparisons were made between low and high tidal volume ventilation as well as across five PEEP levels. RESULTS: At both low (6 mL/kg) and high (10 mL/kg) tidal volume ventilation, PaO2/FIO2 increased with increasing PEEP, up to 20 cmH2O. Similar changes in static compliance were not evident. Static compliance was highest at PEEP of 10 and 15 cmH2O, regardless of tidal volume. With PEEP set at 5 cmH2O, static compliance was significantly lower with 6 mL/kg than with 10 mL/kg tidal volumes. Overall, static compliance was lowest for both tidal volume conditions with PEEP set at 25 cmH2O. CONCLUSION: Low tidal volume ventilation with PEEP set at 5 cmH2O results in poor oxygenation and compliance in patients with moderate to severe acute lung injury. Similarly, PEEP set at 25 cmH2O did not improve oxygenation or compliance.

Adolescent↗