Ethics of emerging technologies and their transition to accepted practice: intestinal transplant for short bowel syndrome.

Parental counseling becomes complex when considering the use of emerging technologies, especially if it is unclear whether the level of evidence is sufficient to transform the proposed therapy into accepted practice. This paper addresses ethical issues underlying medical decision-making and counseling in the setting of emerging treatments, when long-term outcomes are still in the process of being fully validated. We argue that the ethical transition of emerging technologies, ideally from ethically impermissible to permissible, to obligatory, depends primarily on two factors: outcome data (or prognosis) and treatment feasibility. To illustrate these points, we will use intestinal transplant for short bowel syndrome (SBS) as a specific example. After reviewing the data, this paper will identify the ethical justifications for both comfort care only and intestinal transplant in patients with ultra SBS, and argue that both are ethically permissible, but neither is obligatory. The approach outlined will not only be valuable as ultra SBS outcomes data continue to change, but will also be applicable to other novel therapies as they emerge in perinatal medicine.

The role of a pediatric ethics committee in the newborn intensive care unit.

Institutional Ethics Committees are commonly available in hospitals with newborn intensive care units, and may serve as a valuable resource for staff and parents dealing with difficult ethical decisions. Many clinicians may be unaware of when the committee might be helpful, or how it functions. After a brief historical introduction, two cases are presented as illustrations of pediatric ethics committee function. The first involves consideration of cardiac surgery for an infant with ventricular septal defect and Trisomy 13. The second involves disagreement between staff and parents regarding possible provision of cardio-pulmonary resuscitation in a terminally ill newborn. Principles and considerations often brought to bear in committee deliberations are reviewed for each case. Neonatologists, staff and families should be aware of this potentially valuable resource, and are encouraged to use it for situations of moral distress, conflict resolution or ethical uncertainty.

Who is performing medical procedures in the neonatal intensive care unit?

OBJECTIVE: Owing to resident work-hour reductions and more permanent personnel in the newborn intensive care unit (NICU), we sought to determine if pediatric housestaff are missing learning opportunities in procedural training due to non-participation. STUDY DESIGN: A prospective, observational study was conducted at an academic NICU using self-reported data from neonatal personnel after attempting 188 procedures on 109 neonates, and analyzed using Fisher's exact and χ (2)-tests. RESULT: Housestaff first attempted 32% of procedures (P<0.001) and were less likely to make attempts early in the academic year (P<0.001). There was no significant difference in attempts based on urgency of situation (P=0.742). Of procedures performed by non-housestaff personnel, 93% were completed while housestaff were present elsewhere in the unit. CONCLUSION: Pediatric housestaff performed the minority of procedures in the NICU, even in non-urgent situations, and were often uninvolved in other procedures, representing missed learning opportunities.

Selective resuscitation in premature twins: an ethical analysis.

Selective resuscitation refers to the practice of providing resuscitative efforts to one or some (but not all) infants born in the setting of multiple gestation. When one fetus is known to have a severe anomaly or severe growth restriction, parents are sometimes offered this option. In the setting of extreme prematurity, in the absence of an anomaly or severe growth restriction, parents are generally expected to make one unified decision for all the infants involved. The introduction of the Outcome Estimator, a tool that provides the ability to make individual outcome predictions for each fetus in a multiple gestation at borderline gestational age, based on contributing variables such as weight and gender, has led to the ethical dilemma of whether parents in this setting should also be offered the option of selective resuscitation. No convincing ethical argument for denying the parents the right to decide for each individual infant is apparent.

Patient selection for neonatal extracorporeal membrane oxygenation: beyond severity of illness.

OBJECTIVE: To explore how neonates with respiratory failure are selected for extracorporeal membrane oxygenation (ECMO) once severity of illness criteria are met, and to determine how conflicts between ECMO providers and parents over the initiation of ECMO are addressed. STUDY DESIGN: A cross-sectional study was conducted using a data collection survey, which was sent to the directors of neonatal respiratory ECMO centers. RESULT: The lowest birth weight and gestational age at which respondents would consider placing a neonate on ECMO were frequently below recommended thresholds. There was wide variability in respondents' willingness to place neonates on ECMO in the presence of conditions such as intraventricular hemorrhage and hypoxic ischemic encephalopathy. The number of respondents who would never seek to override parental refusal of ECMO was equal to the number who would always do so. CONCLUSION: Significant variability exists in the selection criteria for neonatal ECMO and in how conflicts with parents over the provision of ECMO are resolved.

Parental authority, patient's best interest and refusal of resuscitation at borderline gestational age.

Potential conflict exists when parents refuse a medical intervention for their child that the physician feels obligated to provide. For the anticipated delivery of a preterm newborn, this conflict might exist if the parents refuse resuscitation. At borderline viability, most neonatologists are likely to respect the parents' wishes. However, there will be some gestational age threshold above which the physician will feel compelled to resuscitate despite parental refusal, and will be ethically justified in doing so. The location of that threshold should be determined by the application of sound ethical reasoning, rather than relying on habit or arbitrary standards. That reasoning should include an honest assessment of the benefits and burdens to the child, short-term and long-term, of attempted resuscitation, made in light of relevant mortality and morbidity data. However, a rational analysis will also require consideration of whether the patient's best interest standard should be strictly applied, or whether the interests of others, such as family members, should also be taken into account.

Effect of artificial surfactant on pulmonary function in preterm and full-term lambs.

We hypothesized that agents very different from surfactant may still support lung function. To test this hypothesis, we instilled FC-100, a fluorocarbon, and Tween 20, a detergent, which have higher minimum surface tensions and less hysteresis than surfactant, into 15 full-term and 14 preterm lambs. FC-100 and Tween 20 were as efficient as natural surfactant in improving gas exchange and compliance in preterm lambs with respiratory failure. Dynamic compliance correlated with the equilibrium surface tension of the alveolar wash in both full-term (P less than 0.02) and preterm (P less than 0.008) lambs. Functional residual capacity in full-term and preterm lambs was lower after treatment with the two test agents than with surfactant, findings consistent with qualitative histology. Oxygenation in full-term lambs correlated with mean lung volumes (P less than 0.003), suggesting that the hysteresis and/or low minimum surface tension of surfactant may improve mean lung volume, and hence oxygenation, by maintaining functional residual capacity. The effects of the test agents suggest that agents with biophysical properties different from surfactant may still aid lung expansion.

Corticosteroids and intratracheal surfactant both alter the distribution between the airways and lung tissue of intratracheally administered radiolabeled phosphatidylcholine in the preterm rabbit.

Developmental differences exist regarding quantitative aspects of surfactant phosphatidylcholine clearance from the alveolar space and its subsequent reutilization. We wished to further extend observations of this nature to prematurely delivered rabbits undergoing mechanical ventilation. In addition we tested the hypothesis that prenatal corticosteroid exposure and/or intratracheal surfactant at birth would produce alterations in the lung's clearance of phosphatidylcholine from the airways. Pregnant does were injected with either Ringer's lactate or betamethasone on days 25 and 26 of gestation. Fetuses were delivered at 27 days and given by intratracheal injection either surfactant or one-half strength Ringer's lactate, both of which were trace labeled with [3H]phosphatidylcholine. Fetuses then underwent mechanical ventilation for periods of time ranging from 10 to 120 min. Following ventilation, alveolar lavage and lung tissue were examined to determine the distribution of [3H]phosphatidylcholine between these two compartments. Antenatal corticosteroid exposure was associated with decreased recovery of the radiolabel from the alveolar space and increased recovery of the label from the lung tissue in comparison to control fetuses. Intratracheal surfactant was associated with persistence of the radiolabel within the alveolar space. Therapy with both of these modalities produced a radiolabel distribution that resembled that seen in fetuses receiving intratracheal surfactant alone.

Antenatal steroids, postnatal surfactant, and pulmonary function in premature rabbits.

Antenatal corticosteroids reduce the incidence of the respiratory distress syndrome and improve pulmonary mechanics at least in part by mechanisms other than surfactant stimulation. We measured several aspects of pulmonary function in rabbits to better understand the mechanisms involved. Seven does were given intramuscular betamethasone and six were given vehicle on days 25 and 26 of gestation. Delivery was on day 27 (term = 31). Half of the fetuses from each litter were given rabbit surfactant before the first breath. All fetuses were then ventilated at a consistent tidal volume for 1 h. Pulmonary function tests included static and dynamic compliance, expiratory time constant, stress relaxation, total lung resistance, and total lung conductance. Steroid or surfactant treatment increased dynamic compliance, and the effects of both together were greater than either alone. Static compliance was affected more by surfactant than steroids, whereas lung resistance and conductance were affected more by steroids. The differences in action of the two therapies help account for the increased dynamic compliance seen with combination therapy.

Surface tension and pulmonary compliance in premature rabbits.

In vitro surface properties of pulmonary surfactant thought to be essential to its ability to increase pulmonary compliance include minimum surface tension less than 10 dyn/cm and large surface tension variability and hysteresis. We tested four surface-active agents (Tween 20, a detergent; and FC-100, FC-430, and FC-431, industrial fluorocarbons), all lacking these properties, for their ability to increase pulmonary compliance in surfactant-deficient premature rabbits. Fetal rabbits were delivered by cesarean section at 27 days (full term = 31 days) and injected via tracheostomy with 50% lactated Ringer solution, adult rabbit surfactant, or one of the four experimental agents. Dynamic compliance was measured using 1 h of mechanical ventilation followed by alveolar lavage. Each experimental agent produced a dynamic compliance significantly higher than 50% lactated Ringer solution and statistically equal to or greater than natural surfactant. Equilibrium surface tension of the agents and minimum and equilibrium surface tension of the alveolar washes each correlated with compliance (P less than 0.05). This suggests that some surface properties of pulmonary surfactant believed to be essential are not, although surface tension does seem to play a role in pulmonary compliance.

Congenital lobar emphysema. The roles of CT and V/Q scan.

An infant with congenital lobar emphysema of the left upper lobe presented with unusually severe mediastinal shift and underwent computed tomography (CT) and radionuclide V/Q scans. The V/Q scan confirmed the non-functioning nature of the hyperinflated lobe while the CT scan depicted the abnormal anatomy as well as the normal morphologic characteristics of the remaining lung thus allowing for safe and appropriate surgical management.

Reutilization of surfactant phosphatidylglycerol and lysophosphatidylcholine by adult rabbits.

Adult rabbits reutilize the phosphatidylcholine (PC) of surfactant much less efficiently than developing rabbits (22% vs. 95%). Comparisons of reutilization efficiency of other components of surfactant in adult rabbits have not been determined. We injected adult rabbits intratracheally with [3H]dipalmitoylphosphatidylcholine (DPPG) mixed with [14C]lysophosphatidylcholine (lysoPC) and natural surfactant or [14C]DPPC mixed with [3H]dipalmitoylphosphatidylglycerol (DPPG) and natural surfactant. Recovery in the alveolar wash and lamellar bodies of labelled DPPC, lysoPC and DPPG was determined at different times after injection. By plotting the ratio of [3H]DPPG to [14C]DPPC in the alveolar wash versus time after injection we found that phosphatidylglycerol was reutilized with an efficiency of only 0-7% which was much less than the reutilization of PC in these animals. At early times after injection, adult rabbits injected with [14C]lysoPC had a ratio of [14C]PC in their alveolar wash to lamellar bodies that was larger than 1.0. By comparison, 3-day old rabbits injected intratracheally with [14C]lysoPC had a ratio of [14C]PC in alveolar wash to lamellar bodies less than 1.0 at the earliest times measurable. Thus adult rabbits demonstrate a pathway for accumulation of PC in their alveolar space prior to its appearance in lamellar bodies. This was not detected in developing rabbits. As in developing rabbits, adult rabbits reutilize the phosphatidylglycerol of surfactant less efficiently than the PC of surfactant.

Betamethasone increases pulmonary compliance in part by surfactant-independent mechanisms in preterm rabbits.

Antenatal exposure to corticosteroids is known to increase the pulmonary compliance of preterm animals. We wished to determine whether this was due solely to alteration in lung surfactant content. Rabbit does were injected with either vehicle alone or betamethasone on days 25 and 26 of gestation. Fetuses were delivered at 27 days and given either 50% lactated Ringer's or intratracheal natural surfactant prior to their first breath. Fetuses were mechanically ventilated at a tidal volume of 12 ml/kg for 60 min with periodic compliance measurements. Following ventilation an alveolar lavage was collected for phosphatidylcholine determination. Some fetuses did not undergo ventilation but had saline compliance studies instead. Fetuses given intratracheal surfactant had a higher dynamic compliance than fetuses exposed to antenatal corticosteroids (0.55 +/- 0.01 versus 0.48 +/- 0.02 ml/cm H2O/kg, respectively). Fetuses exposed to antenatal corticosteroids and given intratracheal surfactant had a dynamic compliance (0.66 +/- 0.02) that was greater than those exposed to either single therapy. This was found despite an alveolar surfactant content equal to that in fetuses receiving intratracheal surfactant alone. Saline compliance at birth was significantly greater for fetuses exposed antenatally to steroids. These data imply the existence of a nonsurfactant mechanism by which antenatal corticosteroids increase fetal pulmonary compliance.