Death and Dying 1987-2017: The Destination Is the Same, the Journey Is Different.

OBJECTIVE: A personal reflection on the changing landscape with regard to case mix, care, and staffing and how mortality and expectations have evolved over the past 30 years in a multidisciplinary Pediatric Critical Care Unit in a Quaternary level academic institution in Canada. CONCLUSIONS: Many of the preventable deaths have been prevented with Public Health initiatives. Death now is increasingly in complex patients with complicated treatment regimes in a society that has increasingly unrealistic expectations of what modern medicine can do. Many of these complex children do not die but are dependent on our technology and skill set-something we are often ill prepared for.

Retrospective Application of New Pediatric Ventilator-Associated Pneumonia Criteria Identifies a High-Risk Population.

OBJECTIVES: To promote standardization, the Centers for Disease Control and Prevention introduced a new ventilator-associated pneumonia classification, which was modified for pediatrics (pediatric ventilator-associated pneumonia according to proposed criteria [PVAP]). We evaluated the frequency of PVAP in a cohort of children diagnosed with ventilator-associated pneumonia according to traditional criteria and compared their strength of association with clinically relevant outcomes. DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. PATIENTS: Critically ill children (0-18 yr) diagnosed with ventilator-associated pneumonia between January 2006 and December 2015 were identified from an infection control database. Patients were excluded if on high frequency ventilation, extracorporeal membrane oxygenation, or reintubated 24 hours following extubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for PVAP diagnosis. Primary outcome was the proportion of subjects diagnosed with PVAP. Secondary outcomes included association with intervals of care. Two hundred seventy-seven children who had been diagnosed with ventilator-associated pneumonia were eligible for review; 46 were excluded for being ventilated under 48 hours (n = 16), on high frequency ventilation (n = 12), on extracorporeal membrane oxygenation (n = 8), ineligible bacteria isolated from culture (n = 8), and other causes (n = 4). ICU admission diagnoses included congenital heart disease (47%), neurological (16%), trauma (7%), respiratory (7%), posttransplant (4%), neuromuscular (3%), and cardiomyopathy (3%). Only 16% of subjects (n = 45) met the new PVAP definition, with 18% (n = 49) having any ventilator-associated condition. Failure to fulfill new definitions was based on inadequate increase in mean airway pressure in 90% or FIO2 in 92%. PVAP was associated with prolonged ventilation (median [interquartile range], 29 d [13-51 d] vs 16 d [8-34.5 d]; p = 0.002), ICU (median [interquartile range], 40 d [20-100 d] vs 25 d [14-61 d]; p = 0.004) and hospital length of stay (median [interquartile range], 81 d [40-182 d] vs 54 d [31-108 d]; p = 0.04), and death (33% vs 16%; p = 0.008). CONCLUSIONS: Few children with ventilator-associated pneumonia diagnosis met the proposed PVAP criteria. PVAP was associated with increased morbidity and mortality. This work suggests that additional study is required before new definitions for ventilator-associated pneumonia are introduced for children.

Pediatric Hematopoietic Stem Cell Transplant and Intensive Care: Have Things Changed?

OBJECTIVES: Mortality for pediatric patients who require intensive care posthematopoietic stem cell transplant still remains high. Previously at our institution, survival rates were 44% for patients who required mechanical ventilation posthematopoietic stem cell transplant. We conducted a review of patients to identify whether there has been any improvement in survival over the past 12 years and to identify any risk factors that contribute to mortality. DESIGN: Retrospective chart review. SETTING: PICU and hematopoietic stem cell transplant unit of a single tertiary children's hospital. PATIENTS: Children less than 18 years old undergoing hematopoietic stem cell transplant who required admission to the ICU between January 2000 and December 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 350 separate admissions to the ICU for 206 patients posthematopoietic stem cell transplant. Median Age was 9.3 years (range, 1-17 yr). Median time from hematopoietic stem cell transplant to admission was 35 days (interquartile range, 13-152 d), and 59% of patients were male. Survival to ICU discharge for all admissions was 75%, which equated to 57% of all patients. Of the admissions that required invasive mechanical ventilation, 48% survived to ICU discharge, with a survival to ICU discharge of 36% if there was more than one admission requiring mechanical ventilation. Survival to ICU discharge was 33% if renal replacement therapy was required. Mechanical ventilation, inotrope/vasopressor use, and number of organ dysfunction within an admission were predictors of mortality. Having an underlying malignant condition or an autologous hematopoietic stem cell transplant was associated with a more favorable outcome. CONCLUSIONS: This is the largest single-center series for pediatric patients who require intensive care posthematopoietic stem cell transplant and demonstrates that this group of patients still faces high mortality. There has been an improvement in survival for those patients who require renal replacement therapy and also for patients who require mechanical ventilation more than once; however, the need for mechanical ventilation still remains a significant predictor of mortality.

Effect of humidity on the stability of lung surfactant films adsorbed at air-water interfaces.

The effect of humidity on the film stability of Bovine Lipid Extract Surfactant (BLES) is studied using the captive bubble method. It is found that adsorbed BLES films show distinctly different stability patterns at two extreme relative humidities (RHs), i.e., bubbles formed by ambient air and by air prehumidified to 100% RH at 37 degrees C. The differences are illustrated by the ability to maintain low surface tensions at various compression ratios, the behavior of bubble clicks, and film compressibility. These results suggest that 100% RH at 37 degrees C tends to destabilize the BLES films. In turn, the experimental results indicate that the rapidly adsorbed BLES film on a captive bubble presents a barrier to water transport that retards full humidification of the bubble when ambient air is used for bubble formation. These findings necessitate careful evaluation and maintenance of environmental humidity for all in vitro assessment of lung surfactants. It is also found that the stability of adsorbed bovine natural lung surfactant (NLS) films is not as sensitive as BLES films to high humidity. This may indicate a physiological function of SP-A and/or cholesterol, which are absent in BLES, in maintaining the extraordinary film stability in vivo.

Effect of humidity on lung surfactant films subjected to dynamic compression/expansion cycles.

The surface activity of bovine lipid extracted surfactant (BLES) preparations used in surfactant replacement therapy is studied in dynamic film compression/expansion cycles as a function of relative humidity, surfactant concentration, compression rate, and compression periodicity. BLES droplets were formed in a constrained sessile droplet configuration (CSD). Images obtained during cycling were analyzed using axisymmetric drop shape analysis (ADSA) to yield surface tension, surface area, and drop volume data. The experiments were conducted in a chamber that allowed both humid (100% RH), and "dry" air (i.e. less than 20% RH) environments. It was observed that in humid environments BLES films are not stable and tend to have poor surface activity compared to BLES films exposed to dry air. Further analysis of the data reveal that if BLES films are compressed fast enough (i.e. at physiological conditions) to avoid film hydration, lower minimum surface tensions are achieved. A film hydration-relaxation mechanism is proposed to explain these observations.

Cumulative fluid intake minus output is not associated with ventilator weaning duration or extubation outcomes in children.

OBJECTIVE: The effect of fluid balance on respiratory outcomes for critically ill children has not been evaluated. The only indicator of fluid balance routinely recorded across our intensive care units was estimated fluid intake and output. We sought to determine whether cumulative intake minus output (I-O) at the start of weaning predicted weaning duration and whether cumulative I-O at extubation predicted extubation failure. DESIGN: Prospective observational study. SETTING: Ten pediatric intensive care units. PATIENTS: Cumulative I-O was recorded daily for 301 mechanically ventilated children (<18 yrs of age) from November 1999 through April 2001. INTERVENTIONS: Cumulative I-O was recorded during a study of weaning strategies and extubation failure in which mechanical ventilation of the majority of patients during weaning and extubation was managed according to a protocol that did not include fluid balance indicators. Outcomes were the time to successful removal of ventilatory support and the rate of initial extubation failure. MEASUREMENTS AND MAIN RESULTS: Relationships between cumulative I-O and outcomes were assessed by means of proportional hazards and logistic regression. The mean cumulative I-O per kilogram of ideal body weight at the start of weaning was 101 mL (sd, 180). Cumulative I-O at the time weaning was initiated did not predict duration of mechanical ventilator weaning. The mean cumulative I-O per kilogram of ideal body weight at extubation was 136 mL (sd, 237). Cumulative I-O at extubation did not predict extubation outcome. There was an association between cumulative I-O at extubation and the duration of weaning in cases not managed by a protocol. CONCLUSION: Although routinely recorded, cumulative fluid I-O does not appear to have clinical utility in cases managed according to a mechanical ventilator protocol in which tidal volume and oxygenation on minimal levels of ventilator support are systematically tested.

Poly(ethylene glycol) (PEG) enhances dynamic surface activity of a bovine lipid extract surfactant (BLES).

Shortage or malfunction of pulmonary surfactant in alveolar space leads to a critical condition termed respiratory distress syndrome (RDS). Surfactant replacement therapy, the major method to treat RDS, is an expensive treatment. In this paper, the effect of poly(ethylene glycol) (PEG) to improve dynamic surface activity of a bovine lipid extract surfactant (BLES) was studied by axisymmetric drop shape analysis (ADSA) and a captive bubble method. The activity of BLES+PEG mixtures was compared to that of a natural surfactant containing surfactant proteins A and D. When PEG was added into BLES mixtures, the surface tension hysteresis of BLES films was minimized when the films were compressed by more than 50%. PEG also helps to quickly restore surfactant films after film collapse. Thus, as far as surface tension effects go, the findings suggest that PEG might be used as a substitute for surfactant-associated protein SP-A in therapeutic surfactant products, and might also be used to reduce the amount of BLES required in clinical applications.

Fluorocarbons facilitate lung recruitment.

OBJECTIVE: "Open the lung and keep it open" is increasingly accepted as a fundamental principle for mechanical ventilation. However, it is sometimes very difficult, or impossible, to recruit the diseased lung. We questioned whether one could facilitate recruitment by using a low dose of fluorocarbon in a model previously shown to be non-recruitable by conventional sustained inflation maneuvers. DESIGN AND SETTING: Experimental prospective study in a university laboratory. ANIMALS AND INTERVENTIONS: Nine saline-lavaged rabbits subjected to prolonged large tidal volume mechanical ventilation to establish significant lung injury were randomly allocated to two groups: control [High Frequency Oscillation (HFO) alone: n=4] or 1 ml/kg fluorocarbon (FC) treated (HFO/FC: n=5) for 2+1 h (experiment 1). An additional four similarly prepared animals were treated by single-lung instillation of 0.5 ml/kg dose of fluorocarbon and underwent serial computerized tomography scans at a series of predetermined step-wise pressure increase in both lungs (experiment 2). MEASUREMENTS AND RESULTS: In experiment 1 there was a very significant improvement in oxygenation in HFO/FC group (PaO(2) increased from 108 mmHg to 424+/-81 mmHg; P<0.05) while there was no significant change in the control group. In experiment 2 lung volumes were determined using three-dimensional reconstruction. The lung having fluorocarbon showed a 2.4-fold increase in lung volume at inflation pressure of 15 cmH(2)O compared to the lung without fluorocarbon. CONCLUSIONS: We propose that the low equilibrium surface tension and positive spreading coefficient of fluorocarbon facilitates lung recruitment by ungluing adherent surfaces in this model of lung injury.

Neonatal hyperkalemic-hypocalcemic cardiac arrest associated with initiation of blood-primed continuous venovenous hemofiltration.

We report hyperkalemic-hypocalcemic cardiac arrest at the initiation of blood-primed continuous venovenous hemofiltration in a 3-wk-old infant. Although hyperkalemia with massive transfusion has been reported and hemodynamic instability is not infrequent at the initiation of continuous venovenous hemofiltration in critically ill children, cardiac arrest in these circumstances is extremely rare at our institution and has not been reported in the literature. We report the case and discuss management strategies for blood-primed extracorporeal circuits.

Comparison of loss in lung volume with open versus in-line catheter endotracheal suctioning.

OBJECTIVE: Disconnecting the endotracheal tube from the ventilator causes significant loss in lung volume, which is further exacerbated by suctioning. In-line catheter suction systems have putative benefits over open catheter suction by maintaining positive pressure, thereby minimizing hypoxemia and hemodynamic instability. However, there is a theoretical risk of generating large negative airway pressures and auto-cycling of the ventilator with in-line catheter suction systems. We studied the effects on lung volume with both these techniques. DESIGN: Open, randomized, crossover, clinical trial. SETTING: Pediatric critical care unit. PATIENTS: Fourteen paralyzed patients, age 6 days to 13 yrs. INTERVENTIONS: Each patient, acting as his or her own control, was suctioned with an in-line catheter suction system and open catheter suction. Each suction maneuver was standardized. Changes in lung volume were measured by inductance plethysmography. Heart rate, blood pressure, and oxygen saturation were continuously monitored. MEASUREMENTS AND MAIN RESULTS: Total lung volume loss was greater with open catheter suction compared with in-line catheter suction systems (p = .008). The most significant amount of lung volume loss associated with open catheter suction appears to be related to ventilator disconnection, rather than actual suctioning. Patients with decreased pulmonary compliance (< 0.8 mL/cm H2O/kg) demonstrated a greater loss in lung volume, both absolute and relative, as a result of ventilator disconnection (p = .038 and .006, respectively). Patients suctioned with open catheter suction desaturated to a greater extent than patients suctioned with in-line catheter suction (p = .026). There was evidence of ventilator triggering during the actual suction maneuver in all patients during in-line catheter suctions. CONCLUSIONS: The most significant loss in lung volume during suctioning occurs primarily during ventilator disconnection. Hence, open catheter suction results in greater lung volume loss when compared with in-line catheter suction. We suggest that in-line catheter suction is preferable, especially in patients with significant lung disease and who require high positive end-expiratory pressures, to avoid alveolar derecruitment and exacerbating hypoxemia during endotracheal tube suctioning.

Nosocomial urinary tract infections in children in a pediatric intensive care unit: a follow-up after 10 years.

OBJECTIVE: To define nosocomial urinary tract infection (NUTI) rates in a pediatric intensive care unit, and determine whether practice recommendations have been sustained after 10 yrs. DESIGN: Retrospective, descriptive observational study followed by point prevalence audits of duration of urinary tract catheterization. SETTING: A 32-bed pediatric intensive care unit in a multidisciplinary, 300-bed, university-affiliated tertiary care hospital. SUBJECTS: The retrospective review included patients admitted to the pediatric intensive care unit between December 1997 and July 1999 who developed a NUTI. The audits of duration of urinary tract catheterization were performed in December 2001. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the development of NUTI. Out of 2,832 consecutive admissions, 25 patients developed 27 episodes of NUTI (rate, 0.95/100 admissions). Previous surgery for congenital heart disease was the primary risk factor for NUTI. All 18 patients for whom the duration of catheterization was available had been catheterized for at least 3 days. Gram-negative bacilli and yeast accounted for 82% of NUTI pathogens. Twenty percent of bacterial pathogens were antibiotic resistant. Audits of the duration of urinary tract catheterization done on five separate occasions revealed that the mean duration of catheterization ranged from 3.5 to 4.7 days, with a peak absolute value of 16 days. CONCLUSIONS: NUTIs in children in our pediatric intensive care unit were associated with previous cardiovascular surgery and with urinary tract catheterization of at least 3 days. The need for careful fluid monitoring by catheterization must be balanced against the increased risk of catheter-related urinary tract infection. Removal of urinary catheters at the earliest opportunity will prevent many infections. Ongoing education or innovative strategies will be required to sustain optimal practice.

Safety and efficacy of ketorolac in children after cardiac surgery.

OBJECTIVE: To evaluate the nephrotoxic and opioid-sparing effects of ketorolac in children after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: A Cardiac Critical Care Unit in a university-affiliated children's hospital. SUBJECTS: Children less than 18 years of age who underwent low-risk cardiac surgery from July 2002 to December 2005. RESULTS: Among 248 children studied, 108 received ketorolac and 140 did not. The ketorolac group was older, included a larger proportion of atrial septum defect repairs and a smaller proportion of ventricular septum defect repairs compared to the control group. The median change in serum creatinine did not differ between the ketorolac group and the control group (% change [IQR]); 12% [1-25] increase versus 12% [-3 to 31] increase, P = 0.86. On postoperative day 0 or 1, the ketorolac group received less opioids than control group. There was no difference in duration of mechanical ventilation or in length of stay between groups. CONCLUSION: Ketorolac started in the first 12 h after a low-risk cardiac surgery in children is not associated with a measurable difference in renal function. The data suggest that ketorolac may be effective in reducing the exposure to opioids. Further studies are required to define subsets of children after cardiac surgery who could safely benefit from ketorolac therapy to reduce pain.

Heparin-bonded central venous catheters do not reduce thrombosis in infants with congenital heart disease: a blinded randomized, controlled trial.

BACKGROUND: Infants with congenital heart disease who require central venous lines are at increased risk of thrombosis. Heparin-bonded catheters provide protection from thrombotic events in some children. However, heparin-bonded catheters may not be as effective in infants

Effect of compressed bovine lipid extract surfactant films on oxygen transfer.

In the lungs, oxygen transfer from the inspired air to the capillary blood needs to cross the surfactant lining layer of the alveoli. Therefore, the gas transfer characteristics of lung surfactant film are of fundamental physiological interest. However, previous in vitro studies-most relied on the Langmuir-type balance-fail to cover the low surface tension range (i.e., less than the equilibrium surface tension of approximately 25 mJ/m2) due to film leakage. We have recently developed a novel in vitro experimental strategy, the combination of axisymmetric drop shape analysis and captive bubble technique (ADSA-CB), in studying the effect of surfactant films on interfacial gas transfer (Langmuir 2005, 21, 5446). In the present work, ADSA-CB is used as a micro-film-balance to study the effect of compressed bovine lipid extract surfactant (BLES) films on oxygen transfer. A low surface tension ranging from approximately 25 mJ/m2 to 2 mJ/m2 is studied. The experimental results suggest that lung surfactant films at a low surface tension near 2 mJ/m2 provide resistance to oxygen transfer, as indicated by a decrease of 30-50% in the mass transfer coefficient (kL) of oxygen in BLES suspensions with respect to water. At higher surface tension (i.e., >6 mJ/m2), the resistance to oxygen transfer is only modest, i.e., the decrease in kL is less than 20% compared to water. The experimental results suggest that lung surfactant plays a role in oxygen transfer in the pulmonary system.

Protective strategies of high-frequency oscillatory ventilation in a rabbit model.

High-frequency oscillatory ventilation (HFOV) causes less severe lung injury than conventional mechanical ventilation (CMV) but the optimal frequency for HFOV has not been determined. We hypothesized that 15 Hz HFOV would be more protective than 5 Hz HFOV in a rabbit model of acute lung injury. Surfactant-depleted rabbits were ventilated at 15 Hz or 5 Hz HFOV for 4 h, or not ventilated, to characterize the extent of lung injury before HFOV. PaO(2) and PaCO(2) were measured throughout the experiment, and lung myeloperoxidase (MPO) activity, neutrophil infiltration, and histopathological changes were determined. There were no statistically significant differences in PaO(2) and PaCO(2) between groups (p > 0.05). Neutrophil counts (p = 0.013), airway injury scores (p = 0.007), airspace injury scores (p = 0.029), and total lung injury scores (p = 0.014) differed between non-HFO-ventilated and HFOV animals. Comparing the 2 HFOV regimens, 15 Hz ventilation yielded a lower tissue neutrophil score (p = 0.005). MPO activity, neutrophil count, airway injury score, airspace injury score, and total lung injury score parameters did not differ significantly between the HFOV groups (p > 0.150). We concluded that both frequencies of HFOV efficiently restored O(2) and CO(2) exchange in a rabbit model of severe lung injury, and that 5 Hz HFOV increased neutrophil infiltration relative to 15 Hz HFOV.

Chitosan enhances the in vitro surface activity of dilute lung surfactant preparations and resists albumin-induced inactivation.

Chitosan is a natural, cationic polysaccharide derived from fully or partially deacetylated chitin. Chitosan is capable of inducing large phospholipid aggregates, closely resembling the function of nonionic polymers tested previously as additives to therapeutic lung surfactants. The effects of chitosan on improving the surface activity of a dilute lung surfactant preparation, bovine lipid extract surfactant (BLES), and on resisting albumin-induced inactivation were studied using a constrained sessile drop (CSD) method. Also studied in parallel were the effects of polyethylene glycol (PEG, 10 kD) and hyaluronan (HA, 1240 kD). Both adsorption and dynamic cycling studies showed that chitosan is able to significantly enhance the surface activity of 0.5 mg/mL BLES and to resist albumin-induced inactivation at an extremely low concentration of 0.05 mg/mL, 1000 times smaller than the usual concentration of PEG and 20 times smaller than HA. Optical microscopy found that chitosan induced large surfactant aggregates even in the presence of albumin. Cytotoxicity tests confirmed that chitosan has no deleterious effect on the viability of lung epithelial cells. The experimental results suggest that chitosan may be a more effective polymeric additive to lung surfactant than the other polymers tested so far.

Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans.

OBJECTIVES: We conducted a randomized controlled trial of the effects of remote ischemic preconditioning (RIPC) in children undergoing repair of congenital heart defects. BACKGROUND: Remote ischemic preconditioning reduces injury caused by ischemia-reperfusion in distant organs. Cardiopulmonary bypass (CPB) is associated with multi-system injury. We hypothesized that RIPC would modulate injury induced by CPB. METHODS: Children undergoing repair of congenital heart defects were randomized to RIPC or control treatment. Remote ischemic preconditioning was induced by four 5-min cycles of lower limb ischemia and reperfusion using a blood pressure cuff. Measurements of lung mechanics, cytokines, and troponin I were made pre- and postoperatively. RESULTS: Thirty-seven patients were studied. There were 20 control patients and 17 patients in the RIPC group. The mean age and weight of the RIPC and control patients were not different (0.9 +/- 0.9 years vs. 2.2 +/- 3.4 years, p = 0.4; and 6.9 +/- 2.9 kg vs. 11.5 +/- 10 kg, p = 0.06). Bypass and cross-clamp times were not different (80 +/- 24 min vs. 88 +/- 25 min, p = 0.3; and 55 +/- 13 min vs. 59 +/- 13 min, p = 0.4). Levels of troponin I postoperatively were greater in the control patients compared with the RIPC group (p = 0.04), indicating greater myocardial injury in control patients. Postoperative inotropic requirement was greater in the control patients compared with RIPC patients at both 3 and 6 h (7.9 +/- 4.7 vs. 10.9 +/- 3.2, p = 0.04; and 7.3 +/- 4.9 vs. 10.8 +/- 3.9, p = 0.03, respectively). The RIPC group had significantly lower airway resistance at 6 h postoperatively (p = 0.009). CONCLUSIONS: This study demonstrates the myocardial protective effects of RIPC using a simple noninvasive technique of four 5-min cycles of lower limb ischemia and reperfusion. These novel data support the need for a larger study of RIPC in patients undergoing cardiac surgery.

Effect of surfactant on interfacial gas transfer studied by axisymmetric drop shape analysis-captive bubble (ADSA-CB).

A new method combining axisymmetric drop shape analysis (ADSA) and a captive bubble (CB) is proposed to study the effect of surfactant on interfacial gas transfer. In this method, gas transfer from a static CB to the surrounding quiescent liquid is continuously recorded for a short period (i.e., 5 min). By photographical analysis, ADSA-CB is capable of yielding detailed information pertinent to the surface tension and geometry of the CB, e.g., bubble area, volume, curvature at the apex, and the contact radius and height of the bubble. A steady-state mass transfer model is established to evaluate the mass transfer coefficient on the basis of the output of ADSA-CB. In this way, we are able to develop a working prototype capable of simultaneously measuring dynamic surface tension and interfacial gas transfer. Other advantages of this method are that it allows for the study of very low surface tensions (<5 mJ/m2) and does not require equilibrium of gas transfer. Consequently, reproducible experimental results can be obtained in a relatively short time. As a demonstration, this method was used to study the effect of lung surfactant on oxygen transfer. It was found that the adsorbed lung surfactant film shows a retardation effect on oxygen transfer, similar to the behavior of a pure DPPC film. However, this retardation effect at low surface tensions is less than that of a pure DPPC film.

Effect of humidity on the adsorption kinetics of lung surfactant at air-water interfaces.

The in vitro adsorption kinetics of lung surfactant at air-water interfaces is affected by both the composition of the surfactant preparations and the conditions under which the assessment is conducted. Relevant experimental conditions are surfactant concentration, temperature, subphase pH, electrolyte concentration, humidity, and gas composition of the atmosphere exposed to the interface. The effect of humidity on the adsorption kinetics of a therapeutic lung surfactant preparation, bovine lipid extract surfactant (BLES), was studied by measuring the dynamic surface tension (DST). Axisymmetric drop shape analysis (ADSA) was used in conjunction with three different experimental methodologies, i.e., captive bubble (CB), pendant drop (PD), and constrained sessile drop (CSD), to measure the DST. The experimental results obtained from these three methodologies show that for 100% relative humidity (RH) at 37 degrees C the rate of adsorption of BLES at an air-water interface is substantially slower than for low humidity. It is also found that there is a difference in the rate of surface tension decrease measured from the PD and CB/CSD methods. These experimental results agree well with an adsorption model that considers the combined effects of entropic force, electrostatic interaction, and gravity. These findings have implications for the development and evaluation of new formulations for surfactant replacement therapy.

Circumstances surrounding end of life in a pediatric intensive care unit.

OBJECTIVE: Approximately 60% of deaths in pediatric intensive care units follow limitation or withdrawal of life-sustaining treatment (LST). We aimed to describe the circumstances surrounding decision making and end-of-life care in this setting. METHODS: We conducted a prospective, descriptive study based on a survey with the intensivist after every consecutive death during an 8-month period in a single multidisciplinary pediatric intensive care unit. Summary statistics are presented as percentage, mean +/- standard deviation, or median and range; data are compared using the Mantel-Haenszel test and shown as survival curves. RESULTS: Of the 99 observed deaths, 27 involved failed cardiopulmonary resuscitation; of the remaining 72, 39 followed withdrawal/limitation (W/LT) of LST, 20 were do not resuscitate (DNR), and 13 were brain deaths (BDs). Families initiated discussions about forgoing LST in 24% (17 of 72) of cases. Consensus between caregivers and staff about forgoing LST as the best approach was reached after the first meeting with 51% (35 of 68) of families; 46% (31 of 68) required >or=2 meetings (4 not reported). In the DNR group, the median time to death after consensus was 24 hours and for W/LT was 3 hours. LST was later withdrawn in 11 of 20 DNR cases. The family was present in 76% (45 of 59) of cases when LST was forgone. The dying patient was held by the family in 78% (35 of 45) of these occasions. CONCLUSIONS: More than 1 formal meeting was required to reach consensus with families about forgoing LST in almost half of the patients. Families often held their child at the time of death. The majority of children died quickly after the end-of-life decision was made.