Use of surfactant beyond respiratory distress syndrome, what is the evidence?

Surfactant replacement therapy is currently approved by the United States Food and Drug Administration (FDA) for premature infants with respiratory distress syndrome (RDS) caused by surfactant deficiency due to immaturity. There is strong evidence that surfactant decreases mortality and air leak syndromes in premature infants with RDS. However, surfactant is also used "off-label" for respiratory failure beyond classic RDS. This review discusses current evidence for the use of off-label surfactant therapy for (1) term infants with lung disease such as meconium aspiration syndrome (MAS), pneumonia/sepsis, and congenital diaphragmatic hernia (2) premature infants after 72 h for acute respiratory failure, and (3) the use of surfactant lavage. At last, we briefly describe the use of surfactants for drug delivery and the current evidence on evaluating infants for surfactant deficiency.

Intratracheal instillation of budesonide suspension versus normal saline on oxidative stress in neonates with meconium aspiration syndrome.

BACKGROUND: Presently, the efficacy of neonatal resuscitation techniques via interventions such as oral, nasal, and endotracheal suction for preventing meconium aspiration syndrome (MAS) after delivery has not been satisfactory. OBJECTIVE: This study aimed to investigate the role of intratracheal instillation of budesonide on oxidative stress in MAS. METHODS: Sixty-two neonates with MAS admitted to Huai'an Maternity and Child Healthcare Hospital from January 2018 to June 2020 were divided into a study group (intratracheal instillation of 2 ml budesonide suspension; n = 31) and a control group (intratracheal instillation of 2 ml normal saline; n = 31). Collect data from two groups of patients and evaluate clinical outcomes, including oxygenation index (OI), as well as serum total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI) and 8-Isoprostane before treatment and 72h after admission. RESULTS: We found no statistical differences in mortality, complication rate, total oxygen inhalation time, OI before treatment and 72h after admission between the two groups of neonates with MAS, while the duration of invasive respiratory support in the study group was significantly shorter than in the control group. Also, serum TAC, TOS, OSI and 8-isoprostane levels were not statistically different before treatment between the two groups. After 72h of admission, OSI and 8-Isoprostane in neonates with MAS in the study group were much lower than those in the control group. TOS, OSI, 8-Isoprostane in the control group and 8-Isoprostane in the study group were significantly higher than those before treatment. As for TAC and TOS, no significant differences were observed between the two groups. CONCLUSION: Intratracheal instillation of budesonide was shown to alleviate oxidative stress and shorten invasive ventilation time in neonates with MAS.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57 percent, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Inflammatory markers in meconium induced lung injury in neonates and effect of steroids on their levels: a randomized controlled trial.

PURPOSE: To determine the levels of TNFa and IL-1beta in tracheal aspirates of neonates with meconium aspiration syndrome (MAS) and to ascertain whether the use of steroids by systemic or nebulized routes suppresses the levels of these inflammatory markers. METHODS: This was a double blind, randomized, controlled, prospective, interventional study done over one year period in the neonatal unit of the Lady Hardinge Medical College. Fifty-one babies of MAS which were randomly distributed into three groups; control, systemic and nebulized steroids; were included in the study. Methyl prednisolone was given intravenously in the dosage of 0.5 mg/kg/day in two divided doses while nebulized budecort was given in a dosage of 50 mcg/dose twice daily. Tracheal aspirates were taken on day 1, 3 and 4 and were analyzed for TNFa and IL-1b by ELISA technique. RESULTS: TNFa in tracheal aspirates showed an increasing trend in babies of MAS in first four days, thereby signifying an inflammatory process underlying the condition. The levels of TNFa were suppressed by use of steroids. Higher levels of TNFa were associated with longer stay in hospital. IL-1b did not show any significant correlation. CONCLUSIONS: TNFa is associated with meconium-associated inflammation. Its level is suppressed with the use of steroids and can also be used to assess prognosis of neonates with MAS.

Different doses of exogenous surfactant for treatment of meconium aspiration syndrome in newborn rabbits

OBJETIVO: Avaliar os efeitos de duas diferentes doses de surfactante exógeno sobre a mecânica pulmonar e sobre a regularidade da expansão do parênquima pulmonar em coelhos recém-nascidos. MÉTODO: Coelhos recém-nascidos foram traqueostomizados e randomizados em quatro grupos de estudo: grupo-Controle, sem aspiração de mecônio; grupo MEC, com aspiração de mecônio e sem tratamento com surfactante exógeno; grupos S100 e S200, ambos com aspiração de mecônio e tratados respectivamente com 100 e 200 mg/kg de surfactante exógeno (produzido e fornecido pelo Instituto Butantan). Os animais dos 4 grupos foram ventilados por 25 minutos. A mecânica pulmonar foi avaliada a partir dos valores de complacência dinâmica, pressão ventilatória, volume-corrente e volume pulmonar máximo (curva P-V). A análise histológica foi feita calculando-se o diâmetro alveolar médio (Lm) e o índice de distorção através do desvio padrão do Lm. Utilizou-se ANOVA One Way com a = 0,05. RESULTADOS: Após 25 minutos de ventilação, os valores de complacência dinâmica (ml/cm H2O.kg) foram: 0,87± 0,07 (Controle); 0,49±0,04 (MEC*); 0,67±0,06 (S100) e 0,67±0,08 (S200) e de pressão ventilatória (cm H2O): 9,0± 0,9 (Controle); 16,5±1,7 (MEC*); 12,4±1,1 (S100) e 12,1±1,5 (S200). Ambos os grupos tratados tiveram padrão de expansão do parênquima mais homogêneo em relação aos animais não tratados: índice de distorção de 7,5± 1,9 (Controle); 11,3±2,5 (MEC*); 5,8±1,9 (S100) e 6,7±1,7 (S200) (*p < 0,05 vs outros grupos). CONCLUSÕES: Animais tratados com surfactante mostraram melhora significativa da mecânica pulmonar e maior homogeneidade do padrão de expansão pulmonar comparados ao grupo não tratado. Não houve influência das doses de surfactante utilizadas.

Comparación de dos pautas de dosificación de gentamicina en el recién nacido / Comparison of two gentamicin dosing schedules in the newborn

Introducción: La gentamicina es uno de los antibióticos más utilizado en el tratamiento de las infecciones bacterianas graves del recién nacido y diferentes pautas de dosificación de gentamicina han sido recomendadas en este grupo poblacional. Objetivo: Comparar las concentraciones séricas, la eficacia y la toxicidad de dos pautas de dosificación de gentamicina en recién nacidos a término y pretérmino. Material y métodos: Se evaluó prospectivamente a 200 recién nacidos que recibieron tratamiento con gentamicina. En el grupo A (n = 100) se administró según una pauta de múltiples dosis diarias (2,5-3,5 mg/kg/dosis cada 12-18 h), dependiendo de la edad posnatal y las concentraciones séricas de creatinina. En el grupo B (n = 100) se administró en pauta de única dosis diaria (4-5 mg/kg/dosis cada 24-48 h), según la edad posnatal y posconcepcional. Entre ambos grupos se compararon las concentraciones pico y valle séricas de gentamicina, los datos generales y la prevalencia de nefrotoxicidad y ototoxicidad. Resultados: Las concentraciones pico de gentamicina fueron significativamente superiores (8,2 ± 0,22 μg/ml frente a 5,9 ± 0,13 μg/ml; p £ 0,001) y las concentraciones valle fueron significativamente inferiores (0,9 ± 0,06 μg/ml frente a 1,7 ± 0,08 μg/ml; p £ 0,001) en el grupo B. No hubo diferencias significativas entre ambos grupos respecto a la eficacia clínica, o a la prevalencia de nefrotoxicidad u ototoxicidad. Conclusiones: La pauta de gentamicina en única dosis diaria es efectiva, segura y disminuye el riesgo de concentraciones séricas fuera de rango terapéutico en recién nacidos pretérmino y a término (AU)

Introduction: Gentamicin is widely used in full-term neonates as empirical therapy for early-onset suspected or proven sepsis. Several dosing schedules for gentamicin have been recommended for this neonatal population. Objective: To compare gentamicin serum levels, efficacy and toxicity of two dosing schedules in term and preterm newborns. Material and methods: The study included 200 newborns who were started on gentamicin therapy. Group A (N = 100) was prescribed a multiple-daily dosing regimen and Group B (N = 100) on a once-daily dosing regimen. Newborns in Group A received gentamicin at 2.5-3.5 mg/kg/dose q12-18 h depending on postnatal age and serum creatinine levels, and newborns in Group B received 4-5 mg/kg/dose q24-48 h depending on postconceptional and postnatal age. All peak and trough serum drug levels, demographic data, and markers of potential nephrotoxicity and ototoxicity were compared. Results: Peak serum gentamicin levels were significantly higher (8.2 ± 0.22 μg/ml vs. 5.9 ± 0.13 μg/ml; p £ 0.001) and trough levels were significantly lower (0.9 ± 0.06 μg/ml vs. 1.7 ± 0.08 μg/ml; p £ 0.001) in Group B than in Group A. There was no significant difference between the groups either in the clinical failure rate or in the nephrotoxicity or ototoxicity outcomes. Conclusions: Once-daily dosing regimen of gentamicin in preterm and term newborns is safe and effective, with a reduced risk of serum drug concentrations falling outside the therapeutic range (AU)