A mathematical approximation for the solution of a static indentation test

The aim of this study was to compare the incidence of acute adverse events and long-term outcome of two different surfactant dosing procedures in respiratory distress syndrome (RDS). The effects of two surfactant dosing procedures on the incidence of transient hypoxia and bradycardia, gas exchange, ventilatory requirements and 28 d outcome were compared. The patients, comprising 102 infants (birthweight 600-2000 g) with RDS on mechanical ventilation with FiO2 > or = 0.4, were randomized at 2-24 h to receive 200 mg kg(-1) of Curosurf; in 56 it was given by bolus delivery, and in 55 by a simplified technique (dose given in 1 min via a catheter introduced through a side-hole in the tracheal tube adaptor. The baby's position was not changed and ventilation was not interrupted). Two additional surfactant doses (100 mg kg(-1)) were also given, by the same method, if ventilation with FiO2 > or = 0.3 was needed 12 and 24 h after the initial dose. The number of episodes of hypoxia and/or bradycardia was similar in both groups. A slight and transient increase in PaCO2 was observed in the side-hole group. The efficacy of the surfactant, based on oxygenation improvement, ventilator requirements, number of doses required and incidence of air leaks, was similar. No differences were observed in the incidence of intraventricular haemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia or survival. In conclusion, a simplified surfactant dosing procedure not requiring fractional doses, ventilator disconnection, changes in the baby's position or manual bagging was found to be as effective as bolus delivery. The number of dosing-related transient episodes of hypoxia and bradycardia was not decreased by the slow, 1 min, side-hole instillation procedure.     

Junctional tachycardia during radiofrequency ablation of the slow pathway in patients with AV nodal reentrant tachycardia: effects of autonomic blockade

BACKGROUND: Exogenous surfactant treatment of hyaline membrane disease is known to modify the pattern of radiological changes on the chest radiograph. OBJECTIVES: To analyse and attempt to explain the radiological changes observed after exogenous surfactant treatment. Materials and methods. Thirty-nine premature infants with typical hyaline membrane disease. RESULTS: Transient asymmetrical clearing with better aeration of the right lung in the absence of malposition of the tip of the endotracheal tube was observed in nine cases (23 %). This asymmetry was patchy in one case. It was due to a complication of mechanical ventilation in three cases [pneumothorax (n = 2) and pneumomediastinum (n = 1)]. In the other six cases, asymmetrical clearing could be related to the anatomical position of the right main bronchus, which facilitates distribution of surfactant to the right lung. However, the course of these premature infants was similar to that of infants with symmetrical chest radiological findings after treatment. CONCLUSIONS: Asymmetrical clearing of chest radiographs, sometimes patchy, after surfactant treatment requires exclusion of pneumothorax or infection but has no influence on clinical outcome.     

Combined effects of antenatal corticosteroids and surfactant supplementation on the outcome of very low birth weight infants

Antenatal corticosteroids in preterm pregnancy may result in the reduction of the incidence of respiratory distress syndrome (RDS) and neonatal mortality. It is well known that postnatal use of surfactant in very low birth weight (VLBW) infants with RDS results in decreased neonatal morbidity and mortality. To evaluate the additive beneficial effects of combined antenatal corticosteroids and postnatal use of rescue surfactant on the outcome of VLBW infants, we retrospectively reviewed 286 maternal/infant charts of preterm infants with gestational ages 23 to 32 weeks and birth weights 501 to 1500 gm who were born at our institution from 1991 through 1994. Of the 87 (30%) infants who were treated with corticosteroids before birth, 41 (47%) had RDS, and of the 199 (70%) infants who were not treated with corticosteroids before birth, 162 (81%) had RDS (p < 0.001). The infants who had RDS and who were treated with corticosteroids before birth had a decreased incidence of pulmonary air leaks and a decreased need for diuretic therapy. In addition, they had a significant reduction in O2 requirement and ventilator settings as reflected by FIO2, mean airway pressure, ventilator rate, O2 index, and A-aDO2 before they received the first dose of rescue surfactant (p < 0.05 to p < 0.01) in contrast to other VLBW infants who had RDS and who were not treated with corticosteroids before birth. We conclude that antenatal corticosteroid therapy in threatened premature labor combined with the use of postnatal rescue surfactant is associated with a decreased incidence of RDS and may be beneficial for reducing the severity of RDS and improving the eventual outcome of VLBW infants.     

Randomised, controlled trial of nasal continuous positive airway pressure in the extubation of infants weighing 600 to 1250 g

AIM: To determine whether extubation to nasal continuous airway pressure (NCPAP) results in a greater proportion of infants remaining free of additional ventilatory support for one week after extubation compared with those extubated directly to headbox oxygen. METHODS: A randomised, controlled, clinical trial was conducted at the neonatal intensive care unit of the Royal Women's Hospital, Melbourne, of infants with birthweights between 600 and 1250 g, ventilated via an endotracheal tube for more than 12 hours, requiring less than 50% oxygen, a ventilator rate < or = 20/minute, considered by the clinical management team to be ready for extubation. Infants were randomly allocated either to NCPAP or to oxygen administered via a headbox. Success was defined by no requirement for additional ventilatory support over the week following extubation. Failure criteria were (i) apnoea; (ii) absolute increase in oxygen requirement greater than 15% above than required before extubation; or (iii) respiratory acidosis (pH < 7.25 with pCO2 > 6.67 kPa). RESULTS: Thirty one of 47 (66%) infants were successfully extubated to NCPAP compared with 18 of 45 (40%) for headbox oxygen. The increase in failure rate in the headbox group was due primarily to increased oxygen requirements in this group. Of the 27 who failed headbox oxygen, 26 were given a trial of NCPAP and 13 did not require endotracheal reintubation. There was no significant difference between the groups in the total number of days of assisted ventilation or the duration of inpatient stay. CONCLUSIONS: NCPAP applied prophylactically after endotracheal extubation reduces the incidence of adverse clinical events that lead to failure of extubation in the seven days after extubation. This reduction is clinically important. The benefits of NCPAP do not seem to be associated with an increased incidence of unwanted side effects.     

Comparison of alveolar ventilation, oxygenation, pressure support, and respiratory system resistance in response to noninvasive versus conventional mechanical ventilation in foals

OBJECTIVE: To compare the efficacy of positive pressure ventilation applied through a mask versus an endotracheal tube, using anesthetized/paralyzed foals as a model for foals with hypoventilation. ANIMALS: Six 1-month-old foals. PROCEDURE: A crossover design was used to compare the physiologic response of foals to 2 ventilatory techniques, noninvasive mask mechanical ventilation (NIMV) versus endotracheal mechanical ventilation (ETMV), during a single period of anesthesia and paralysis. Arterial pH, PaO2, PaCO2, oxygen saturation, end-tidal CO2 tension, airway pressures, total respiratory system resistance, resistance across the upper airways (proximal to the midtracheal region), and positive end-expiratory pressures (PEEP) were measured. Only tidal volume (VT; 10, 12.5, and 15 ml/kg of body weight) or PEEP (7 cm of H2O) varied. RESULTS: Compared with ETMV, use of NIMV at equivalent VT resulted in PaCO2 and pH values that were significantly higher, but PaO2 was only slightly lower. Between the 2 methods, peak airway pressure was similar, but peak expiratory flow was significantly lower and total respiratory resistance higher at each VT for NIMV. Delivery of PEEP (7 cm of H2O) was slightly better for ETMV (7.1 +/- 1.3 cm of H2O) than for NIMV (5.6 +/- 0.6 cm of H2O). CONCLUSION: These data suggest that use of NIMV induces similar physiologic effects as ETMV, but the nasal cavities and mask contribute greater dead space, manifesting in hypercapnia. Increasing the VT used on a per kilogram of body weight basis, or the use of pressure-cycled ventilation might reduce hypercapnia during NIMV. CLINICAL RELEVANCE: Use of NIMV might be applicable in selected foals, such as those with hypoventilation and minimal changes in lung compliance, during weaning from endotracheal mechanical ventilation, or for short-term ventilation in weak foals.     

Comparison of inspiratory work of breathing between flow-triggered and pressure-triggered demand flow systems in rabbits

OBJECTIVES: Flow-triggered continuous positive airway pressure decreases the inspiratory work of breathing in adults when compared with pressure-triggered continuous positive airway pressure. However, the effect of flow-triggered continuous positive airway pressure on work of breathing in neonates is not known. Our objective was to determine if flow-triggering was superior to pressure triggering in the presence of narrow endotracheal tubes, such as those tubes used in neonates. DESIGN: Prospective evaluation using within-animal comparison of flow-triggering and pressure-triggering demand flow systems. SETTING: The animal laboratory in a university hospital. SUBJECTS: Six spontaneously breathing white rabbits, tracheostomized and intubated with 3- and 4-mm inner diameter endotracheal tubes. INTERVENTIONS: The animals were connected to a ventilator through a standard respiratory circuit. The ventilator was randomly operated in the following modes: flow-triggered continuous positive airway pressure, pressure-triggered continuous positive airway pressure, flow-triggered with 5 cm H2O pressure support ventilation, and pressure-triggered with 5 cm H2O pressure support ventilation. MEASUREMENTS AND MAIN RESULTS: Esophageal pressure, airway pressure, and flow signals were monitored. Control data were obtained while the rabbits were breathing room air through the endotracheal tube. With 3-mm inner diameter endotracheal tubes, the negative deflection of esophageal pressure during flow-triggered continuous positive airway pressure was significantly less than control; however, negative deflection of esophageal pressure during pressure-triggered continuous positive airway pressure did not significantly differ from control. The application of 5 cm H2O pressure support ventilation with flow-triggering decreased negative deflection of esophageal pressure significantly compared with flow-triggered continuous positive airway pressure, pressure-triggered continuous positive airway pressure, and control. With endotracheal tube inner diameter of 4 mm, flow-triggered continuous positive airway pressure and pressure-triggered continuous positive airway pressure did not show any differences compared to control. Negative deflection of esophageal pressure differed under all conditions except control when results with the 3-mm inner diameter endotracheal tube were compared with the 4-mm inner diameter endotracheal tube. CONCLUSIONS: Flow-triggering is superior to pressure-triggering in the presence of a 3-mm inner diameter endotracheal tube. This difference was not clear with a 4-mm inner diameter endotracheal tube. The size of the endotracheal tube may be the most important variable in evaluating the approach used to ventilate small neonates.     

Tracheal pressure triggering a demand-flow continuous positive airway pressure system decreases patient work of breathing

OBJECTIVES: Triggering a ventilator "ON" at the carinal end of the endotracheal tube decreases imposed work of breathing by bypassing the resistance imposed by the breathing circuit and the endotracheal tube. We compared work of breathing during spontaneous ventilation between three methods of triggering the ventilator "ON": a) conventional pressure triggering from inside the ventilator; b) flow-by triggering; or c) tracheal pressure triggering at the carinal end of the endotracheal tube. We hypothesized that the work of breathing would be substantially decreased with tracheal pressure triggering compared with conventional pressure and flow-by methods in patients receiving continuous positive airway pressure. DESIGN: Clinical, prospective study. SETTING: University teaching hospital. PATIENTS: Fourteen adults diagnosed with acute respiratory failure. INTERVENTIONS: All patients were breathing spontaneously at an FIO2 of 0.30 to 0.40 and received 5 cm H2O of continuous positive airway pressure. Three different methods of triggering the ventilator while set in the continuous positive airway pressure mode were administered in random order. MEASUREMENTS AND MAIN RESULTS: Real-time measurements of esophageal pressure and tidal volume were integrated with a respiratory monitor (CP-100, Bicore, Riverside, CA) that uses the Campbell diagram to calculate total work of breathing. Imposed work of breathing was calculated by integrating tidal volume with the pressure at the carinal end of the endotracheal tube. Physiologic work of breathing was calculated by subtracting imposed work of breathing from the total work of breathing. Breathing frequency, the index of rapid shallow breathing (breathing frequency/tidal volume), peak inspiratory flow rate demand, exhaled minute ventilation, and the duration of respiratory muscle contraction assessed by the ratio of inspiratory time to total cycle time were also measured. Data were analyzed by Friedman's repeated-measures analysis of variance on ranks. Alpha was set at .05 for statistical significance. Imposed work of breathing decreased to approximately zero during tracheal pressure triggering. As a result, total work of breathing decreased by approximately 40% compared with the flow-by and conventional methods. During tracheal pressure triggering only, airway pressure increased above baseline pressure to approximately 11 cm H2O, which resembled pressure-support ventilation. Also, during tracheal pressure triggering, tidal volume and peak inspiratory flow rate were significantly increased, while the pressure-time product and the index of rapid shallow breathing were significantly decreased. Hemodynamic status and oxygen saturation were not clinically affected. CONCLUSIONS: The tracheal pressure triggering of a demand-flow continuous positive airway pressure system creates an effect similar to pressure-support ventilation that significantly decreases imposed work of breathing and, thus, total work of breathing. We recommend moving the triggering site of the ventilator to the carinal end of the endotracheal tube.     

Contribution of bronchoalveolar lavage and transbronchial biopsy to diagnosis and prognosis of drug-induced pneumopathies

OBJECTIVE: The purpose of this study was to evaluate three ventilator weaning strategies and to evaluate whether the use of continuous positive airway pressure (CPAP) via a nasopharyngeal or endotracheal tube would increase the likelihood of extubation failure in very low birth weight (VLBW) infants. STUDY DESIGN: We studied prospectively 87 preterm infants (mean +/- SD; birth weight: 1078 +/- 188 g; gestational age: 28.8 +/- 2.2 weeks) who were in the process of being weaned from intermittent mandatory ventilation (IMV). Infants were assigned by systematic sampling to one of the following three treatment groups: (1) direct extubation from IMV (D.EXT) (n = 30); (2) preextubation endotracheal CPAP (ET-CPAP) for 12-24 hr (n = 28); or (3) postextubation nasopharyngeal CPAP (NP-CPAP) for 12-24 hr (n = 29). Failure was defined as the need for resumption of mechanical ventilation within 72 hr of extubation due to frequent or severe apnea and/or respiratory failure (pH < 7.25, PaCO2 > 60 mm Hg, and/or requirement for oxygen FiO2 > 60%). RESULTS: There were no significant differences in failure rates among the three procedures. Failures were 2/30 (7%) in D.EXT; 4/28 (14%) in ET-CPAP; and 7/29 (24%) in the NP-CPAP. There were also no differences in FiO2, PaO2, and respiratory rates before and after discontinuation of IMV among the three groups. PaCO2 values were slightly higher in the NP-CPAP group 12-24 hr after weaning from IMV. CONCLUSION: We were unable to demonstrate a clear difference in extubation outcome by use of CPAP administered via an endotracheal or nasopharyngeal tube when compared to direct extubation from low-rate IMV in VLBW infants.     

Women are at greater risk than men for malpositioning of the endotracheal tube after emergent intubation

OBJECTIVES: To investigate the occurrence of endotracheal tube malpositioning after emergent intubation in critically ill adults and to determine the need for a routine postintubation chest radiography to assess endotracheal tube position. DESIGN: Prospective study. SETTING: All adult critical care and acute care units of a 560-bed university teaching hospital. PATIENTS: Study of 297 consecutive intubations (185 intubations in males and 112 intubations in females) in 238 adult patients. METHODS: Emergent endotracheal intubations were performed by resident physicians with supervision from an intensive care unit (ICU) or anesthesia attending physician or an anesthesia resident. After intubation, proper positioning of the endotracheal tube was verified by the intubating physician using clinical criteria, including auscultation of bilateral breath sounds, symmetric chest expansion, and palpation of the endotracheal tube cuff in the suprasternal notch. The endotracheal tube position relative to the lower anterior incisors or alveolar ridge was recorded using the centimeter markings printed on the endotracheal tube. A chest radiograph was obtained after intubation to verify endotracheal tube position. Appropriate endotracheal tube position on chest radiograph was defined as between > 2 and < or = 6 cm above the carina. MEASUREMENTS AND MAIN RESULTS: Of the 297 intubations, 26 were excluded from analysis because a chest radiograph was not obtained or the patient was not of normal stature. For the remaining 271 intubations, 42 (15.5%) endotracheal tubes were inappropriately placed, according to the radiographic assessment. The percentage of malpositioned endotracheal tubes was significantly higher in women than in men (61.9% vs. 38.1%, respectively; chi-square: p < .001). Thirty-three (78.6%) of 42 malpositioned endotracheal tubes were placed < 2 cm from the carina, with the highest occurrence (24/33) of proximal malposition occurring in women. Positioning of endotracheal tubes using the centimeter markings printed on the tube referenced to the lower incisors did not accurately identify malposition as documented by chest radiograph. CONCLUSIONS: Emergent endotracheal intubations result in a significant occurrence of malpositioned endotracheal tubes that are undetected by clinical evaluation. Malpositioning is not detected by routine clinical assessment, but only by chest radiograph. Women are at greater risk than men for endotracheal tube malpositioning after emergent intubation; in women, the endotracheal tube is more likely to be positioned too close to the carina. A chest radiograph for confirmation of endotracheal tube position after emergent intubation should remain the standard of practice.     

Drug and environmental factors associated with adverse pregnancy outcomes. Part II: Improvement with folic acid

OBJECTIVE: To provide a comprehensive review of periconceptional folic acid supplementation and factors affecting folate supplementation trials. DATA SOURCES: A MEDLINE search was conducted through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included folate, folic acid, neural tube defect, spina bifida, and anencephaly. STUDY SELECTION: Relevant animal and human studies examining the effects of folate were reviewed. DATA EXTRACTION: Data collected included: type of study, folate dosing, dietary folate intake, serum and red blood cell folate concentrations, type of defect(s) studied, vitamin usage, parental risk factors, factors affecting trial results. DATA SYNTHESIS: Nine key factors have been identified that affect outcomes of folic acid supplementation trials. Daily doses of 0.8 mg decreased the occurrence and doses of 4 mg decreased the recurrence of neural tube defects in randomized clinical trials. Since lower folic acid doses were effective in nonrandomized trials, research is needed to determine the lowest effective dosage. Other benefits involving pregnancy outcome are suggested. CONCLUSIONS: Women of childbearing age should take a daily folic acid supplement to reduce the risk of pregnancies resulting in infants with a neural tube defect and other potential adverse pregnancy outcomes. Further health benefits from folic acid supplementation are reviewed in Part III of this series.     

Anesthetic aspects of heart tamponade due to amebic liver abscess. A case report

The problem of tamponade due to rupture of an amoebic abscess, although rare, is extremely complex, and in the planning of the anaesthetic technique the following factors should receive attention: (i) the low cardiac output in which bradycardia, vasodilation, high inflation pressures and excessive fluid load must be avoided: (ii) pulmonary complications in which a double-lumen endotracheal tube should be considered; and (iii) sepsis.     

Electrophysiological effects of ATP on brain neurones

OBJECTIVE: Aminoglycosides have been reported to produce a curare-like neuromuscular blockade in animals at serum concentrations higher than those obtained with traditional dosing (1-2 mg/kg every 8 h) in humans. Aminoglycoside-induced neuromuscular blockade is rarely, if ever, seen in humans with traditional dosing. The recent adoption of once-daily dosing of aminoglycosides has raised concerns about increased potential for this adverse effect because higher serum concentrations are produced. The objective of this study was to determine if once-daily dosing of aminoglycosides inhibits respiratory muscle function. METHOD: Nine mechanically ventilated ICU patients on once-daily dosing of gentamicin 6 mg/kg/day were assessed for respiratory muscle strength by measuring maximum inspiratory pressure (MIP). MIP is a measurement of the maximal negative pressure generated by repeated inhalations against an occluded airway over 20 s. This was measured within 1 hour before (MIPpre) and within 1 hour after each aminoglycoside dose (MIPpost). RESULTS: Mean values for MIPpre and MIPpost were -26.7 cm H2O and -26.5 cm H2O, respectively. The mean difference between MIPpre and MIPpost was -0.2 cm H2O, which was not statistically significant (P > 0.05). CONCLUSION: The effect of gentamicin (6 mg/kg/day) on respiratory muscle function was not statistically, nor clinically significant, and weaning from mechanical ventilation does not seem to be inhibited by once-daily dosing of aminoglycosides as detectable by measurement of MIP.     

A pediatric flexible fiberoptic endoscope

Clinical experience with a flexible fiberoptic endoscope constructed for children is described. The endoscope fits through a 3.5 mm endotracheal tube without removing the tube adaptor. The endoscope was used on artificially ventilated newborns and infants for determining the position of the endotracheal tube, the integrity of the tracheal mucosal wall, and possible obstruction of the endotracheal tube. Visualization of the interior of the tube and the airways can be performed without moving the infant from the incubator. The instrument aids in the management of children requiring prolonged respiratory support. The most common lesion detected was trauma to the tracheal mucosal wall by the suction catheter.     

Continuous measurement of cardiac output by the Fick principle in infants and children: comparison with the thermodilution method

OBJECTIVE: To compare a system that continuously monitors cardiac output by the Fick principle with measurements by the thermodilution technique in pediatric patients. DESIGN: Prospective direct comparison of the above two techniques. SETTING: Pediatric intensive care unit of a university hospital. PATIENTS: 25 infants and children, aged 1 week to 17 years (median 10 months), who had undergone open heart surgery were studied. Only patients without an endotracheal tube leak and without a residual shunt were included. METHODS: The system based on the Fick principle uses measurements of oxygen consumption taken by a metabolic monitor and of arterial and mixed venous oxygen saturation taken by pulse- and fiberoptic oximetry to calculate cardiac output every 20s. INTERVENTIONS: In every patient one pair of measurements was taken. Continuous Fick and thermodilution cardiac output measurements were performed simultaneously, with the examiners remaining ignorant of the results of the other method. RESULTS: Cardiac output measurements ranged from 0.21 to 4.55 l/min. A good correlation coefficient was found: r2 = 0.98; P < 0.001; SEE = 0.41 l/min. The bias is absolute values and in percent of average cardiac output was - 0.05 l/min or - 4.4% with a precision of 0.32 l/min or 21.3% at 2 SD, respectively. The difference was most marked in a neonate with low cardiac output. CONCLUSION: Continuous measurement of cardiac output by the Fick principle offers a convenient method for the hemodynamic monitoring of unstable infants and children.     

Interposed bone grafts to accommodate endosteal implants for retaining mandibular overdentures. A 1-7 year follow-up study

STUDY OBJECTIVES: To examine the effect of timing of an intravenous (i.v.) dose (intraoperative vs. postoperative) of ketorolac tromethamine on pain scores and overall outcome after total abdominal hysterectomy (TAH) and myomectomy. DESIGN: Prospective, randomized, placebo-controlled study. PATIENTS: 248 ASA physical status I and II adult female patients scheduled for elective hysterectomy or myomectomy. INTERVENTIONS: General anesthesia was administered that consisted of thiopental sodium for induction, enflurane or isoflurane in nitrous oxide-oxygen for maintenance, and small doses of fentanyl and midazolam. Patients were randomized into three groups to receive toradol/placebo on a dosing schedule of dose 1 given one-half hour prior to expected end of surgery, dose 2 given on awakening in the postanesthesia care unit, and doses 3, 4, and 5 given at 6, 12, and 18 hours, respectively, after dose 2; Group 1 patients received placebo (saline) for dose 1, ketorolac 60 mg i.v. for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 2 patients received ketorolac 60 mg i.v. for dose 1, placebo for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 3 patients received placebo for all doses. All patients were given i.v. morphine PCA postoperatively, and morphine usages, visual analog pain intensity (VAS) scores, as well as adverse events and median times to recovery milestones were recorded. MEASUREMENTS AND MAIN RESULTS: VAS scores (mean) before dose 2 were significantly lower in Group 2 than Group 1, as were at-rest evaluations at 15 minutes and one hour. Group 2 patients also had decreased morphine requirements as compared to placebo. Both ketorolac groups (Groups 1 and 2) had significantly higher values for patient and observer overall ratings, case of nursing care, and tolerability as compared to placebo (Group 3). There were no significant differences among groups in adverse events or median times to recovery milestones. CONCLUSIONS: Although it is possible to demonstrate an improvement in early postoperative pain scores with intraoperative ketorolac and better overall ratings of ketorolac both intraoperatively and postoperatively as compared with placebo, the lack of clinically significant differences in analgesic efficacy in the two active study groups indicates the need for a careful consideration by the clinician of the risks versus benefits involved in the administration of antiplatelet medication in the perioperative period.     

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin after single and multiple subcutaneous doses to healthy subjects

OBJECTIVES: To understand the pharmacokinetic and pharmacodynamic properties of recombinant human erythropoietin (epoetin alfa) and to continue to optimize dosing regimens by determining whether administration of single high doses of epoetin alfa is as effective as repeated administration. METHODS: Epoetin alfa was administered as single subcutaneous doses of 300, 450, 600, 900, 1200, 1350, 1800, and 2400 IU/kg and in multiple subcutaneous dose regimens: 150 IU/kg 3 times a week for 4 weeks and 600 IU/kg once per week for 4 weeks in 2 open-label, randomized placebo-controlled studies in healthy volunteers. RESULTS: The absorption rate of epoetin alfa after subcutaneous administration was independent of dose, whereas clearance was dose-dependent in that it decreased with increasing dose. There was a linear relationship between response measured as percentage of reticulocytes area under the curve (AUC) and erythropoietin AUC for single doses up to 1800 IU/kg. Beyond the 1800 IU/kg dose, there was a saturation of response. The mean percentage of reticulocytes after single-dose regimens began to increase by days 3 to 4, reached their maximum at days 8 to 11, and returned to baseline values by day 22. In contrast, the mean percentage of reticulocytes after both multiple-dose regimens were maintained above baseline values through day 22 as both regimens stimulated modest but sustained increases in percentage of reticulocytes (1% to 2%). The mean percentage of reticulocytes AUC for 600 IU/kg epoetin alfa given once a week for 4 weeks was apparently greater than the mean percentage of reticulocytes AUC for 150 IU/kg 3 times a week for 4 weeks. Although daily oral iron supplementation was given, mean serum ferritin levels declined by approximately 75% through day 22 in subjects treated with multiple doses of epoetin alfa. CONCLUSIONS: These findings show that the pharmacologic response to epoetin alfa is a function of dose and dosing regimen. Repeated administration of epoetin alfa was more effective in stimulating a reticulocyte response than single-dose administration of the same total amount of epoetin alfa.     

The laryngeal mask airway: a new standard for airway evaluation in thoracic surgery

BACKGROUND: Thoracic surgeons typically perform fiberoptic bronchoscopy (FOB) before thoracotomy, usually on the day of the operation after intubation with a single-lumen endotracheal tube (ETT) and before insertion of a double-lumen ETT. This routine requires two laryngoscopies and two intubations. The laryngeal mask airway (LMA) is an airway device developed in England and approved by the Food and Drug Administration in 1991 for clinical use in the United States. It requires neither mask ventilation nor laryngoscopy and allows FOB visualization of the epiglottis, larynx, and entire trachea. We assessed the LMA as an alternative to a single-lumen ETT for FOB before thoracotomy. METHODS: Through prospective assessment, 50 patients underwent FOB after insertion of an LMA before thoracotomy. Pulse rate, blood pressure, ease of insertion of the LMA, quality of FOB, and complications of LMA insertion were assessed. RESULTS: During LMA insertion, blood pressure and pulse rate increased less than 5% from baseline in all patients. The LMA was inserted successfully in all patients within 10 seconds. No complications occurred as a result of LMA insertion. CONCLUSIONS: Insertion of the LMA causes minimal hemodynamic response. From the time of induction of general anesthesia, insertion of the LMA is quick, simple, and safe and eliminates the need for endotracheal intubation with a single-lumen ETT before double-lumen tube insertion. The LMA, in contrast to the ETT, allows a complete survey of the larynx and trachea. The LMA is autoclavable, reusable, and cost effective. Therefore, in patients who require FOB immediately before thoracotomy, LMA use should be the standard for airway evaluation.     

Ogura and Powers: "Functional restitution of traumatic stenosis of the larynx and pharynx." (Laryngoscope 1964;74: 1081-1110)

The objective of this study was to evaluate the immune response and reactogenicity of a combined hepatitis B, diphtheria, tetanus and whole-cell Bordetella pertussis (DTPw-HBV) vaccine administered to healthy infants at 2, 4 and 6 months of age. A total of 179 infants (6-12 weeks of age) received three doses of DTPw-HBV vaccine. Blood samples for antibody determinations were taken before vaccination, 2 months after the second dose and 1 month after the third dose. Solicited and unsolicited symptoms were recorded by parents in a diary card. All vaccinees had protective levels of anti-HBs [geometric mean titre (GMT): 1526 mIU.ml-1], anti-diphtheria and anti-tetanus antibodies, 1 month after the third dose. Ninety-two percent of the subjects exhibited a response to the B. pertussis component. Most (99.4%) solicited reactions occurred within the first 48 h and the majority were mild or moderate. The safety, immunogenicity of this tetravalent vaccine was demonstrated when it was administered in infants following the 0, 2, 4-month dosing schedule.     

High-pressure destruction kinetics of Listeria monocytogenes on pork

OBJECTIVE: To define the incidence of complications of endotracheal intubation and the factors associated with these complications. STUDY DESIGN: During a 22-month period, 227 intubated infants weighing <1,501 g were followed prospectively in a neonatal intensive care unit. Detailed records of events associated with airway management were kept after every intubation, in addition to clinical data. RESULTS: Eleven infants (4.8%) developed respiratory stridor after extubation which was treated with either systemic corticosteroids, racemic epinephrine and/or reintubation for respiratory failure. Four infants were submitted for bronchoscopy, mild subglottic stenosis with tracheal edema was found in 1 patient, granulation tissue and airway edema were noted in 3 infants. Traumatic intubation, prolonged ventilation, multiple intubations and bacterial colonization of the endotracheal tube were the factors associated with postextubation stridor. CONCLUSIONS: Subglottic stenosis is an infrequent complication of endotracheal intubation with current airway management of very-low-birth-weight infants. Less severe complications are still common, but they are usually amenable to clinical treatment. Bronchoscopy should be performed selectively only in infants with clinical evidence of airway obstruction after extubation.     

Influence of endotracheal tube diameter on forced deflation flow-volume curves in rhesus monkeys

The forced deflation (FD) technique is the recommended gold standard to generate forced expiratory vital capacity (FVC) curves and to measure maximum expiratory flow-volume (MEFV) relationships in intubated infants and children. However, the influence of the endotracheal tube (ETT) on the site of flow limitation, the shape and the analysis of the resultant MEFV curves have not been defined. Nine anaesthetized (thiopentone, 8 mg x kg(-1) x h(-1)) rhesus monkeys (mean weight (+/-SEM) 10+/-1 kg) were intubated consecutively with ETTs of different internal diameters (ID 3.0-5.5 mm, at intervals of 0.5 mm); the largest representing the appropriate ETT size for the animal. Quadruplicate MEFV curves were generated by FD using the standard +40 cmH2Oinsp/-40 cmH2Oexp pressures and recorded at each ETT diameter. The effect of the different ETT diameters on the FD flow-volume curve was analysed by comparing maximum expiratory flows at isovolume points at 50, 25 and 10% FVC (MEF50, MEF25 and MEF10, respectively). The shape of the resulting MEFV curves could be divided into an initial horizontal part (tube-dependent), and a final descending slope (airway-dependent). No difference in FVC occurred irrespective of the ETT size (p>0.05 by analysis of variance (ANOVA)). MEF50 increased with increasing tube diameter (p<0.05). MEF25 remained unchanged using ETTs which were less than 1.5 mm smaller than the largest ETT. Smaller ETTs resulted in significantly reduced MEF25 (p<0.05). MEF10 was not influenced by the ETT size. We conclude that maximum expiratory flows measured by the forced deflation technique are not influenced by an appropriately sized endotracheal tube at lung volumes below 25% forced vital capacity in our monkey model with normal lungs. We postulate that the effect of endotracheal tubes on maximum expiratory flow volume curves in intubated infants might be of similar or even smaller magnitude, which remains to be established.