Impact of vitamin D replacement in adults and elderly in the Middle East and North Africa: a systematic review and meta-analysis of randomized controlled trials.

In the Middle East and North Africa (MENA), a vitamin D dose ≥2000 IU/day may be needed to allow to the majority of the population to reach the target 25-hydroxyvitamin D (25(OH)D) level ≥20 ng/ml. Data in the region on the effect of vitamin D supplementation on various skeletal and extra-skeletal effects are scarce. INTRODUCTION: Hypovitaminosis D is prevalent worldwide, more so in the Middle East and North Africa (MENA). This study aims to determine the effects of vitamin D replacement on the mean difference in 25-hydroxyvitamin D [25(OH)D] level reached and other outcomes, in the MENA. METHODS: This is a meta-analysis of randomized trials from the MENA, administering vitamin D supplementation for at least 3 months, without language or time restriction. We conducted a comprehensive search in seven databases until July 2015. We abstracted data from published reports, independently and in duplicate. We calculated the mean difference (MD) and 95 % CI of 25(OH)D level reached for eligible comparisons, and pooled data using RevMan version 5.3. RESULTS: We identified 2 studies in elderly and 17 in adults; for the latter, 11 were included in the meta-analysis. Comparing a high vitamin D dose (>2000 IU/day) to placebo (nine studies), the MD in 25(OH)D level achieved was 18.3 (CI 14.1; 22.5) ng/ml; p value < 0.001; I 2 = 92 %. Comparing an intermediate dose (800-2000 IU/day) to placebo (two studies), the MD in 25(OH)D level achieved was 14.7 (CI 4.6; 24.9) ng/ml; p value 0.004; I 2 = 91 %. Accordingly, 89 and 71 % of participants, in the high and intermediate dose groups, respectively, reached the desirable level of 20 ng/ml. The risk of bias in the included studies was unclear to high, except for three studies. CONCLUSION: In the MENA region, vitamin D doses ≥2000 IU/day may be needed to reach the target 25(OH)D level ≥20 ng/ml. The long-term safety and the efficacy of such doses on various outcomes are unknown.

Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer.

PURPOSE: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. METHODS: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. RESULTS: The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. CONCLUSIONS: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.

BRAF mutational epidemiology in dysplastic nevi: does different solar UV radiation exposure matter?

BACKGROUND: Proto-oncogene B-Raf (BRAF) mutation rates have been reported in nevi and melanomas of homogeneous Caucasian cohorts. OBJECTIVE: To study the demographics of BRAF mutations in dysplastic nevi of populations with differing potential solar UV radiation exposure. METHODS: Extended BRAF testing for 9 mutations in 125 dysplastic nevi from 101 patients, derived from populations with differing potential UV radiation exposure rates (Lebanon and Saudi Arabia), was performed. Clinical and microscopic parameters were recorded. RESULTS: BRAF mutation status was carried out for 101/125 (80.8%) cases with an overall mutation rate of 62.4% (63/101). V600E (c.1799T > A) was the predominant mutation, found in 61/63 (96.8%) cases. BRAF mutation rate differed significantly by potential UV radiation exposure (Lebanon: 53.4%, Saudi Arabia: 74.4%, P < 0.05). A 43.8% discordant mutation rate (7/16 patients) was found in patients with multiple nevi, including 2 patients with different BRAF mutations. Microscopic examination subdivided the dysplasia into mild (n = 24), moderate (n = 60) and severe (n = 41) with trunk predominance (72.8%). Higher rates of pigment in the stratum corneum were identified in Saudi Arabia (P < 0.05). No statistical significant increase in BRAF mutation rate was noted with advanced architectural and cytological atypia. Parameters associated with a negative BRAF mutation status included upper extremity location, regression, cohesiveness and presence of suprabasal melanocytes (P < 0.05). Positive BRAF mutation status was reasonably predicted by multivariate binary logistic regression by 2 independent predictors: Geographic location and compound nevus type. CONCLUSIONS: In our Near Eastern cohort, the BRAF mutation rate varied significantly by geographic location. In patients with multiple dysplastic nevi examined, discordant BRAF mutation status potentially negates an underlying constitutional predilection.

Predictors of quality of life among multiple sclerosis patients: a comprehensive analysis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a debilitating neurological disease of young people with substantial consequences on patients' quality of life (QOL). A variety of QOL instruments have been used to evaluate the efficacy of treatments. However, no study assessed the role of the different demographic, clinical, physical, social, economic and psychological parameters in the perception of patients with MS of their QOL. METHODS: Two-hundred and one consecutive patients attending outpatient clinics were prospectively studied and objectively assessed using Expanded Disability Status Scale (EDSS), 8-m walk test, and Symbol Digit Modality Test. Patients completed the following questionnaires: MS QOL-54, Hamilton Depression Rating Scale, Fatigue Severity Scale, Brief Pain Inventory Average Pain Score, Drug Side-Effects Severity Scale, Social Support, Religiosity, Physiotherapy and Exercise, and Socioeconomic Profile. Overall, QOL, physical (PHCS) and mental (MHCS) health composite scores were computed as outcome measures from MSQOL-54. RESULTS: Depression, social support, religiosity, education years and living area predicted overall QOL by linear regression (R(2) = 0.43). Unemployment and absence of fatigue correlated with poor and good QOL, respectively. Fatigue, pain, depression, EDSS, social support, MS type and anti-cholinergic treatment predicted PHCS (R(2) = 0.81). Fatigue, pain, depression, education years and social support predicted MHCS (R(2) = 0.70). CONCLUSION: The QOL in patients with MS is not solely determined by physical disability, but rather by the level of social support, living area, depression, level of education, employment, fatigue and religiosity. Accordingly, we suggest that these should be evaluated in every patient with MS as they may be modified by targeted interventions.

Bubble and ventilator-derived nasal continuous positive airway pressure in premature infants: work of breathing and gas exchange.

OBJECTIVE: During bubble nasal continuous positive airway pressure (B-NCPAP), gas flows through the expiratory limb of CPAP tubing submerged underwater to a depth in centimeters considered equal to the desired end expiratory pressure. Ventilator-derived NCPAP (V-NCPAP) controls the delivered pressure at the expiratory orifice. Limited data exist comparing the two forms of NCPAP on work of breathing (WOB) and other short-term respiratory outcomes. We compared WOB and gas exchange between B-NCPAP and V-NCPAP at equivalent delivered nasal prong pressures among a cohort of preterm infants on NCPAP. STUDY DESIGN: We performed a randomized crossover study in 18 premature infants <1500 g (BW 1101±254 g, GA 28±2 weeks, study age 13±8 days (means±s.d.)), who were already on NCPAP for mild respiratory distress, comparing B-NCPAP to V-NCPAP. Each infant was studied at a constant flow rate and varying pressures of 3, 5, 7, 4 and 2 cm H(2)O in that order. Tidal volumes were obtained by calibrated respiratory inductance plethysmography. Intrapleural pressure was estimated by an esophageal catheter. WOB (inspiratory, elastic and resistive) was calculated from pressure volume data. Breathing asynchrony was assessed with phase angle. Comparisons of respiratory rate, heart rate, tidal volume, minute ventilation, breathing asynchrony, lung compliance, oxygen saturation and transcutaneous (Tc) O(2) and CO(2) were also made. RESULT: WOB and most respiratory parameters were not different between B-NCPAP and V-NCPAP. TcO(2) was higher with B-NCPAP compared to V-NCPAP (P=0.01). TcCO(2) was not different. None of the other measured parameters was significantly different between the two devices. CONCLUSION: WOB and ventilation with B-NCPAP and V-NCPAP are similar when equivalent delivered prong pressures are assured. Improved oxygenation with B-NCPAP is intriguing and requires further investigation.

Work of breathing during constant- and variable-flow nasal continuous positive airway pressure in preterm neonates.

BACKGROUND: Constant-flow nasal continuous positive airway pressure (NCPAP) often is used in preterm neonates to recruit and maintain lung volume. Physical model studies indicate that a variable-flow NCPAP device provides more stable volume recruitment with less imposed work of breathing (WOB). Although superior lung recruitment with variable-flow NCPAP has been demonstrated in preterm neonates, corroborating WOB data are lacking. OBJECTIVE: To measure and compare WOB associated with the use of variable-flow versus constant-flow NCPAP in preterm neonates. METHODS: Twenty-four preterm infants who were receiving constant-flow NCPAP (means, SD) and had birth weight of 1024 +/- 253 g, gestational age of 28 +/- 1.7 weeks, age of 14 +/- 13 days, and FIO(2) of 0.3 +/- 0.1 were studied. Variable-flow and constant-flow NCPAP were applied in random order. We measured changes in lung volume and tidal ventilation (V(T)) by DC-coupled/calibrated respiratory inductance plethysmography as well as esophageal pressures at NCPAP of 8, 6, 4, and 0 cm H(2)O. Inspiratory WOB (WOB(I)) and lung compliance were calculated from the esophageal pressure and V(T) data using standard methods. WOB was divided by V(T) to standardize the results. RESULTS: WOB(I) decreased at all CPAP levels with variable-flow NCPAP, with a maximal decrease at 4 cm H(2)O. WOB(I) increased at all CPAP levels with constant-flow CPAP. Lung compliance increased at all NCPAP levels with variable-flow, with a relative decrease at 8 cm H(2)O, whereas it increased only at 8 cm H(2)O with constant-flow NCPAP. Compared with constant-flow NCPAP, WOB(I) was 13% to 29% lower with variable-flow NCPAP. CONCLUSION: WOB(I) is decreased with variable-flow NCPAP compared with constant-flow NCPAP. The increase in WOB(I) with constant-flow NCPAP indicates the presence of appreciable imposed WOB with this device. Our study, performed in neonates with little lung disease, indicates the possibility of lung overdistention at CPAP of 6 to 8 cm H(2)O with the variable-flow device. Further study is necessary to determine the efficacy of variable-flow NCPAP in neonates with significant lung disease and its use over extended periods of time.continuous-flow and variable-flow NCPAP, work of breathing, premature neonates, lung compliance.

Effects of body size on operative, intermediate, and long-term outcomes after coronary artery bypass operation.

BACKGROUND: To investigate the role of body size, if any, on operative and longer term outcomes following coronary artery surgery. METHODS: A total of 3,560 consecutive patients undergoing coronary artery bypass grafting from 1991 to 1997, including 2,401 (67%) males and a mean +/- SD age of 63 +/- 10 years were ranked based on their body mass index (BMI). The association in these patients of preoperative, long-term, and economic data with variations in BMI were studied using regression analyses. Long-term survival was studied using 5-year Kaplan-Meier survival analysis. RESULTS: Operative mortality, myocardial infarction, cerebrovascular accidents, blood transfusions, and length of hospital stay were all increased in the smallest patients (BMI < or = 24 kg/m2). Obesity did not increase adverse operative outcomes except for a greater rate of sternal wound infections occurring with increasing severity of obesity. Direct variable costs were lowest in patients clustered around normal BMI, with cost increasing similarly at low and high extremes. This effect was correlated with similar BMI effects on ventilatory and intensive care requirements. Excluding operative mortality, 5-year survival trends were similarly worse for the smallest (BMI < or = 24) and most severely obese (BMI > 34) patients. Mild obesity (BMI > or = 30 to BMI < 34) did not affect long-term survival. CONCLUSIONS: Among study patients, immediate operative outcomes were adversely affected by small body size, which reflected older age (66 +/- 10 years) and an exaggerated adverse impact of cardiopulmonary bypass. Younger age and smaller effects of cardiopulmonary bypass lead to better operative outcomes in the obese. Long-term outcomes were, however, suboptimal in severely obese patients although that group was the youngest (60 +/- 10 years). In addition to their large body habitus, other factors, including substantial prevalence of diabetes, insulin dependence and hypertension, probably played a significant role in the poor long-term outcome in the severely obese.

Lung recruitment and breathing pattern during variable versus continuous flow nasal continuous positive airway pressure in premature infants: an evaluation of three devices.

OBJECTIVE: To determine whether lung volume changes and breathing pattern parameters differ among 3 devices for delivery of nasal continuous positive airway pressure (CPAP) in premature infants. METHODS: Thirty-two premature infants receiving nasal CPAP for apnea or mild respiratory distress were enrolled. Birth weight was (mean +/- standard deviation) 1081 +/- 316 g, gestational age 29 +/- 2 weeks, age at study 13 +/- 12 days, and fraction of inspired oxygen (FIO(2)) at study.29 +/-.1. Three devices, applied in random order, were studied in each infant: continuous flow nasal CPAP via CPAP prongs, continuous flow nasal CPAP via modified nasal cannula, and variable flow nasal CPAP. After lung recruitment to standardize volume history, changes in lung volume (DeltaV(L)) were assessed at nasal CPAP of 8, 6, 4, and 0 cm H(2)O using calibrated direct current-coupled respiratory inductance plethysmography. RESULTS: DeltaV(L) was significantly greater overall with the variable flow device compared with both the nasal cannula and CPAP prongs. However, DeltaV(L) was not different between the cannula and the prongs. Respiratory rate, tidal volume, thoraco-abdominal asynchrony, and FIO(2) were greater with the modified cannula than for either of the other 2 devices. CONCLUSION: Compared with 2 continuous flow devices, the variable flow nasal CPAP device leads to greater lung recruitment. Although a nasal cannula is able to recruit lung volume, it does so at the cost of increased respiratory effort and FIO(2).

Optimal tracheal tube cuff inflation in infants: implications for mechanical ventilation and respiratory mechanics.

Uncuffed tracheal tubes (TT) are used to intubate infants and children to avoid laryngotracheal tissue injury. The geometric mismatch resulting from such intubation limits the efficacy of mechanical ventilation, and reliability of derived respiratory mechanical properties. This study tested the hypotheses that (1) normal stresses applied to the cuff surface by leak flows during ventilation result in intracuff pressure (Pcuff) fluctuations proportionate to leak magnitudes, and (2) these fluctuations reach a steady minimum when cuff volume reaches a critical value (Vcrit) at which the TT-airway mismatch is removed. Physical model and piglet measurements showed that, during simultaneous cuff inflation and mechanical ventilation, Pcuff consisted of a leak-dependent (Pcuff,l) component that cycles with the ventilator superimposed on a ramp rise due to cuff inflation. The breath-to-breath peak Pcuff,l (max Pcuff,l) decreased as leak flows are reduced, and these were relatively greater for higher ventilator flows and when the load impedance is increased such as by disease. These results describe a reproducible method of TT cuff inflation that removes leaks without increased risk of laryngotracheal tissue injury. Moreover, inflation of the TT cuff more securely improved ventilation efficacy and allowed for accurate respiratory mechanics.

Predictors of gastrointestinal complications in cardiac surgery.

Gastrointestinal problems are infrequent but serious complications of cardiac surgery, with high rates of morbidity and mortality. Predictors of these complications are not well developed, and the role of fundamental variables remains controversial. In a retrospective review of our cardiac surgery experience from July 1991 through December 1997 we found that postoperative gastrointestinal complications were diagnosed in 86 of 4,463 consecutive patients (1.9%). We categorized these 86 patients into 2 groups--Surgical and Medical--according to the method of treatment used for their complications. In the Medical group, 9 of 52 patients (17%) died; in the Surgical group, 17 of 34 (50%) died. By logistic multivariate analysis, we identified 8 parameters that predicted gastrointestinal complications: age greater than 70 years, duration of cardiopulmonary bypass, need for blood transfusions, reoperation, triple-vessel disease, New York Heart Association functional class IV, peripheral vascular disease, and congestive heart failure. Postoperative re-exploration for bleeding was a predictor specific to the Surgical group. Use of an intraaortic balloon pump was markedly higher in the Gastrointestinal group than in the Control group (30% vs 10%, respectively), as was the use of inotropic support in the immediate postoperative period (27% vs 5.6%). Our results suggest that intra-abdominal ischemic injury is a likely contributing factor in most gastrointestinal complications. In turn, the ischemia is probably caused by hypoperfusion due to low cardiac output, hypotension due to blood loss, and intra-abdominal atheroemboli. The derived models are useful for identifying patients whose risk of gastrointestinal complications after cardiac surgery may be reduced by clinical measures designed to counter these mechanisms.

Detecting lung overdistention in newborns treated with high-frequency oscillatory ventilation.

Positive airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV) increases lung volume and can lead to lung overdistention with potentially serious adverse effects. To date, no method is available to monitor changes in lung volume (DeltaVL) in HFOV-treated infants to avoid overdistention. In five newborn piglets (6-15 days old, 2.2-4.2 kg), we investigated the use of direct current-coupled respiratory inductive plethysmography (RIP) for this purpose by evaluating it against whole body plethysmography. Animals were instrumented, fitted with RIP bands, paralyzed, sedated, and placed in the plethysmograph. RIP and plethysmography were simultaneously calibrated, and HFOV was instituted at varying Paw settings before (6-14 cmH(2)O) and after (10-24 cmH(2)O) repeated warm saline lung lavage to induce experimental surfactant deficiency. Estimates of Delta VL from both methods were in good agreement, both transiently and in the steady state. Maximal changes in lung volume (Delta VL(max)) from all piglets were highly correlated with Delta VL measured by RIP (in ml) = 1.01 x changes measured by whole body plethysmography - 0.35; r(2) = 0.95. Accuracy of RIP was unchanged after lavage. Effective respiratory system compliance (Ceff) decreased after lavage, yet it exhibited similar sigmoidal dependence on Delta VL(max) pre- and postlavage. A decrease in Ceff (relative to the previous Paw setting) as Delta VL(max) was methodically increased from low to high Paw provided a quantitative method for detecting lung overdistention. We conclude that RIP offers a noninvasive and clinically applicable method for accurately estimating lung recruitment during HFOV. Consequently, RIP allows the detection of lung overdistention and selection of optimal HFOV from derived Ceff data.

Resource utilization in coronary artery bypass operation: does surgical risk predict cost?

BACKGROUND: Current healthcare trends may render financial risk of cardiac operation a key component of clinical decision making. It has been suggested, based on large cohorts of patients stratified by clinical risk, that the cost of operation can be predicted from models of clinical risk since length of stay (LOS) is highly correlated to clinical risk, and LOS is correlated to hospital costs and charges. Direct correlation of actual surgical costs with surgical risk are lacking. METHODS: Variable direct costs, LOS, and The Society of Thoracic Surgeons predicted mortality risk [STS risk (%)] were collected and analyzed in 628 consecutive patients undergoing coronary artery bypass grafting (CABG) at our institution in 1997. RESULTS: Cost of CABG had a near-normal distribution, and cost in 21 outlier patients (cost > two standard deviations above the mean) was an average 5.3 times normal (median cost). For individual patients, cost was well correlated to LOS (R2 = 0.48) but not with STS risk (R2 = 0.12). LOS was also poorly predicted by STS risk (R2 = 0.09). However, despite its poor prediction of cost, STS risk was an unbiased estimator over the entire population. A result manifested, when patients were grouped into similar risk (<1%, 1-2%, 2+ -3%, 3+ -5%, 5+ -10%, and >10%) cohorts, by high correlation between cost and STS risk (R2 = 0.99), cost and LOS risk (R2 = 0.99), and LOS and STS risk (R2 = 0.97). CONCLUSIONS: Our data demonstrated that, in large CABG cohorts, surgical risk models can accurately predict cost of CABG. However, despite a trend for increasing cost with increasing STS risk, surgical risk models based on preoperative data are poor predictors of cost in individual patients. Use of these models should be limited to analysis of cost trends in cardiac operation, but not for predicting financial risk in individual patients during clinical decision making.

Lung resistance and elastance in spontaneously breathing preterm infants: effects of breathing pattern and demographics.

Reported values of lung resistance (RL) and elastance (EL) in spontaneously breathing preterm neonates vary widely. We hypothesized that this variability in lung properties can be largely explained by both inter- and intrasubject variability in breathing pattern and demographics. Thirty-three neonates receiving nasal continuous positive airway pressure [weight 606-1,792 g, gestational age (GA) of 25-33 wk, 2-49 days old] were studied. Transpulmonary pressure was measured by esophageal manometry and airway flow by face mask pneumotachography. Breath-to-breath changes in RL and EL in each infant were estimated by Fourier analysis of impedance (Z) and by multiple linear regression (MLR). RL(MLR) (RL(MLR) = 0.85 x RL(Z) -0.43; r(2) = 0.95) and EL(MLR) (EL(MLR) = 0.97 x EL(Z) + 8.4; r(2) = 0.98) were highly correlated to RL(Z) and EL(Z), respectively. Both RL (mean +/- SD; RL(Z) = 70 +/- 38, RL(MLR) = 59 +/- 36 cm H(2)O x s x l(-1)) and EL (EL(Z) = 434 +/- 212, EL(MLR) = 436 +/- 210 cm H(2)O/l) exhibited wide intra- and intersubject variability. Regardless of computation method, RL was found to decrease as a function of weight, age, respiratory rate (RR), and tidal volume (VT) whereas it increased as a function of RR. VT and inspiratory-to-expiratory time ratio (TI/TE). EL decreased with increasing weight, age, VT and female gender and increased as RR and TI/TE increased. We conclude that accounting for the effects of breathing pattern variability and demographic parameters on estimates of RL and EL is essential if they are to be of clinical value. Multivariate statistical models of RL and EL may facilitate the interpretation of lung mechanics measurements in spontaneously breathing infants.

Variables predicting reintubation after cardiac surgical procedures.

BACKGROUND: This study sought to determine patient characteristics, processes of care, and intermediate outcomes as predictors of reintubation after cardiac surgical procedures. METHODS: We performed a retrospective case-control study that included all patients undergoing cardiac surgical intervention who required reintubation and an equal number of control patients not requiring reintubation. Putative risk factors were analyzed univariately by chi2, Fisher exact, Student's t, or Mann-Whitney tests. A logistic regression model was developed using data from patients requiring reintubation for cardiorespiratory reasons. RESULTS: Of the 1,000 consecutive patients reviewed, 41 (4.1%) required reintubation (30 [3%] for cardiorespiratory reasons and 11 [1.1] for unplanned operations). Univariate predictors of reintubation (p<0.05) were older age, chronic obstructive pulmonary disease, New York Heart Association functional class IV, preoperative renal failure, lower arterial oxygen tension, insertion of intraaortic balloon pump, longer time in the operating room, longer duration of cardiopulmonary bypass times, positive fluid balance, postoperative renal failure, and worse pulmonary mechanics. Patients requiring reintubation also required a longer initial period of mechanical ventilation (median, 16.3 versus 6.0 hours; p<0.05). Excellent prediction was found with a model consisting of four variables: operating room time, respiratory rate, vital capacity, and chronic obstructive pulmonary disease. CONCLUSIONS: Patients who required reintubation were sicker and had worse respiratory function and more comorbidity. Prompt extubation did not contribute to reintubation. Patients identified as having a high risk for reintubation should be followed up closely, and interventions should be directed to treating the problems leading to reintubation.

Effects of rate and amplitude of breathing on respiratory system elastance and resistance during growth of healthy children.

Intrinsic properties of lung and chest wall tissues can lead to breathing rate (frequency [f]) and amplitude (tidal volume [VT]) dependence of respiratory system resistance (R) and elastance (E). To explore these dependencies on R and E within physiological limits of tidal volume and breathing frequencies during early childhood. we measured airway opening pressure (Pao) and flow (V'ao) in 15 anesthetized, paralyzed, intubated, and mechanically ventilated healthy children (age 1 day to 72 months; weight 2.5-21 kg) at multiple combinations of VT (6, 10, and 14 mL/kg) and frequency (10, 20, and 30 breaths/min). In each instance, R and E were estimated by multiple linear regression applied to the tracheal pressure, flow, and volume (V), assuming a simple series R-E model. R decreased substantially with increasing frequency and weight (Wt), but was unaffected by changes in VT (R = 764Wt(-0.91) x f(-0.57)). E decreased sharply with increasing Wt, was lower at higher VT, and was slightly, yet significantly, increased at higher frequency (E = 2,905Wt(-1.38) x VT(-0.18) x f(0.11)). Such frequency dependence of R and E is consistent with stress adaptive, or viscoelastic, properties of respiratory tissues. The small V dependence of E is similar to that observed in other species under healthy conditions and presumably reflects the combined nonlinear pressure-volume relationships of the healthy parenchymal and chest wall tissues. Lack of VT dependence of R at high inspiratory flow rates suggests that turbulent flows are either not an important form of energy dissipation in the lower airways of children or they are counterbalanced by a decrease in tissue damping at high VT. The above regression models represent the first attempt to quantify simultaneously the separate effects of lung growth as well as rate and amplitude of breathing on R and E. Similar equations based on a larger sample of healthy subjects can provide normative R and E values for comparison with mechanically ventilated children with lung disease.

Factors predisposing to median sternotomy complications. Deep vs superficial infection.

STUDY OBJECTIVES: Median sternotomy infections are a serious complication of cardiac surgery. The purpose of this study was to determine the patient characteristics and operative variables that predict incidence of sternal infection, and possibly its severity. DESIGN: Univariate and multivariate retrospective analysis comparing patient, operative, and post-operative data in patients with and without sternal infections. SETTING: Cardiac surgery program of a 580-bed private hospital in Toledo, Ohio. PATIENTS: We studied 2,317 consecutive (June 1991 to December 1994) patients undergoing cardiac surgery. RESULTS: Forty-one sternal infections were documented. Of these, 21 (0.91%) were deep infections with mediastinal involvement and 20 (0.86%) were superficial. Two patients with deep infections died (2/41, 5%). Ten variables were associated with infection by univariate analysis (p < 0.05), and of these, five were independent predictors by multivariate logistic regression. These predictors were obesity (p < 0.001), insulin-dependent diabetes (p < 0.001), use of internal mammary artery grafts (p = 0.02), surgical reexploration of the mediastinum (p = 0.003), and postoperative transfusions (p = 0.01). Predictors of deep and superficial sternal infection did not differ. Length of hospitalization was substantially longer for patients with deep (32 +/- 21 days) vs superficial infection (13 +/- 10 days). CONCLUSIONS: The present study confirms previous findings that obesity, insulin-dependent diabetes, and internal mammary artery grafting (especially bilaterally) increase the risk of sternal infection. In addition, chest surgical reexploration and blood transfusions were postoperative factors that predisposed patients with median sternotomy to infection. Unlike their associated morbidity and mortality, predictors of deep and superficial sternal infections are similar.

Determinants of prolonged mechanical ventilation after coronary artery bypass grafting.

BACKGROUND: Early extubation of cardiac surgical patients enhances ambulation, improves cardiopulmonary function, and can lead to savings in health care costs. METHODS: We retrospectively examined the role of 48 variables in determining the period of ventilatory support in 507 patients having coronary artery bypass grafting. RESULTS: Fifteen (< 3%) of 507 patients required ventilatory support in excess of 24 hours. Among the remaining patients, extubation was achieved early (< or = 8 hours) (mean time, 5.65 +/- 1.31 hours) in 53% and late (> 8 hours) (mean time, 13.7 +/- 3.4 hours) in 47%. Logistic and linear multivariate regression analyses implicated increased age, New York Heart Association functional class IV, intraoperative fluid retention, postoperative intraaortic balloon pump requirement, and bank blood transfusions as predictors of late extubation. Also, the linear regression linked lower body weight and number of anastomoses (or grafts) to increased mechanical ventilatory support. CONCLUSIONS: Analysis of the fluid balance and cardiopulmonary bypass data suggests that earlier extubation may be achieved by actively reducing fluid retention (eg, by hemoconcentration) and time on bypass (eg, normothermia). Finally, intensive care unit stay and postoperative length of stay were significantly lower in the early versus late extubation groups without an increase in pulmonary complications.

Delayed primary closure of deep sternal wound infections.

Deep infections of the sternum and mediastinum, with prevalence of osteomyelitis and tissue necrosis, were documented in 38 of 8,056 patients (0.47%) who underwent open-heart surgery (1975 through 1994) in our service. The incidences of insulin-dependent diabetes, obesity, and emergency surgery in these patients were relatively high at 39%, 47%, and 18%, respectively. Treatment with antibiotics, débridement, open packing, and delayed closure was administered to 33 patients (87%), with 100% healing. There were no deaths in this group. Flap reconstruction was indicated in 5 gravely ill patients (13%) in whom excessively large wound defects did not allow reapproximation. There were 2 deaths in this group, and 4 reoperations were necessary in the surviving patients because of sequelae arising from flap reconstruction. The overall mortality was 5.3% and the median period of hospitalization was 29 days. The length of stay decreased substantially over the period of this study (median = 21 days, year > or = 1987). Accordingly, we believe that treatment of deep sternal infections with delayed primary closure is safe and effective. Also, given the increased potential for complications and long-term sequelae, we believe that flap reconstruction should be used selectively and should be limited to patients with large defects, uncontrolled mediastinal bleeding, or both.

Serial distribution of airway diameters from input impedance and computed tomography.

Indirect measures of airway diameter such as respiratory system input impedance (Zin) have been widely used to infer or quantify bronchoconstriction, or bronchodilation. One such measure, Zin above 100 Hz has been shown to be primarily influenced by airway geometry and airway walls but not by lung and chest wall tissues. We used a recently developed method based on a complex asymmetrically branched network of tubes with nonrigid walls to analyze Zin from 100 to 2,000 Hz in control and bronchoconstricted (histamine injection) dogs. The resulting estimates of airway diameters indicated that peripheral airways were constricted far more (approximately 30% of their control diameters) than central airways (i.e., 0% in the trachea). Separate measurements of changes in airway diameters were made in an excised dog lung using high resolution computed tomography. The observed changes in airway diameter between lung volumes of total lung capacity (TLC) and functional residual capacity (FRC) were quantitatively consistent with those obtained from Zin data in our control dogs at FRC. We conclude that this systems identification method can be used to estimate the distribution of airway diameters from Zin.