Medical Care |

Medical Care




Microsoft powerpoint - mas.grd rds.2008.10.02 [compatibility mode]

Meconium Aspiration Syndro y first intestinal discharge from newborns is meconium ◦ a viscous, dark green substance composed of intestinal epithelial cells, lanugo, mucus, and intestinal secretions, such as bile. Chief, Division of Neonatology ◦ Intestinal secretions, mucosal cells, and solid elements of swallowed amniotic fluid are the 3 major solid constituents of meconium. Professor of Pediatrics, Pathology and Anatomical ◦ Water is the major liquid constituent, making up 85-95% of meconium. Sciences, and Gynecology-Obstetrics y Intrauterine distress can cause passage of meconium into the ◦ Factors that promote the passage in utero include placental insufficiency, maternal hypertension, preeclampsia, oligohydramnios, and maternal drug abuse, especially of tobacco and cocaine.
y Meconium-stained amniotic fluid may be aspirated during labor and delivery, causing neonatal respiratory distress. y Because meconium is rarely found in the amniotic fluid prior to 34 weeks' gestation, meconium aspiration chiefly affects infants at term Dave Clark emedicine 2004 Pediatric Grand Rounds October 3, 2008 ome - More
m Me onium
Ne England Jour nal of Medic 353(9):946--8, 2005 Sep y The passage of mec in utero accompanies 8% to 20% o -UCLA Medical Center (average 12-13%) of all deliveries ◦ <37 weeks Æ 2% Meconium, the fecal material that ◦ >42 weeks Æ 44% accumulates in the fetal colon throughout ◦ seen predominantly in infants who are SGA and postmature, gestation, is a term derived from the Greek cord complications or other factors compromising the in Beginning with Aristotle's observation of the y MSAF is usually considered to be indicative of fetal association between meconium staining of the amniotic fluid and a sleepy fetal state or y Many MSAF babies exhibit no signs of depression, etc., neonatal depression, obstetricians have been but some brief period of asphyxia could have induced concerned about fetal well-being in the the passage of mec before delivery.
presence of meconium-stained amniotic fluid.
y MAS seen in 4% of MSAF deliveries Fanaroff and Martin 2002, Miller, Fanaroff and Martin Avery 1991, Hansen and Corbet Prenatal Management y presence of MSAF is not always an y passage of meconium in utero: indication of fetal distress in all infants ◦ we think it is associated with asphyxia but data ◦ MSAF may signal fetal hypoxia, but if FHR, pH actually are weak remain normal then outcome usually ◦ ? result of transient parasympathetic stimulation from compr ssion in a neurologicall y combination of MSAF and ominous FHR tracing is often associated with significant ◦ ? natural phenomenon that reflects the maturity of fetal and neonatal asphyxia with accompanying morbidity ◦ most agree that MSAF plus FHR abnormalities are a marker for fetal distress and associated with increased perinatal morbidity Fanaroff and Martin 2002, Miller, Fanaroff and Martin Avery 1991, Hansen and Corbet y Mec in the AF may stain the umb cord, placenta y If aspiration of meconium stained amniotic fluid before, during, and after y when fetal distress is present, gasping may be initiated in utero Æ AF and particulate matter birth occurs, there can be 3 major contained therein may be inhaled into the large pulmonary effects: Î mec aspiration may occur antenatally ◦ airway obstruction y mec inhaled by the fetus may be present in the ◦ surfactant dysfunction trachea or larger bronchi at delivery Æ after air breathing has commenced chemical pneumonitis migration of mec within the lung Fanaroff and Martin 2002, Miller, Fanaroff and Martin Dave Clark emedicine 2004 y areas of atelectasis, resulting from total airway obstruction, adjacent to y areas of overexpansion, from gas trapping in regions with partial obstruction y Î "salt and pepper" appearance on CXRy air leaks ◦ pneumomediastinum◦ pneumothorax y chemical inflammation Æ pneumonitisy in vitro: concentration-dependent inhibition of during inspiration, lower
y animal models: influx of inflammatory cells and protein, however, during expiration, the lower
airways open Æ air can go
inactivation of surfactant, decrease in surf proteins airways collapse and with the
into the alveolar air space
meconium present air cannot leave Æ
air trapping Æ hyperinflation, PTX
Clinical Findings y postmaturityy mec staining – nails, skin, umbilical cordy often perinatal depression ◦ neurologic, resp depression secondary to hypoxia (which precipitated the passage of mec in the first place) y Severe respiratory distress may be present: ◦ Cyanosis◦ End-expiratory grunting◦ Alar flaring◦ Intercostal retractions◦ Tachypnea◦ Barrel chest in the presence of air trapping◦ Rales Dave Clark emedicine 2004 Fanaroff and Martin 2002, Miller, Fanaroff and Martin Fanaroff and Martin 2002, Miller, Fanaroff and Martin Clinical Manif stations y can be a major problem in infants with MAS y clinical symptoms progress over 12-24 y both prenatal and postnatal maladaptation of the hours as mec migrates to the periphery pulmonary circulation may contribute to the y mec ultimately has to be removed by development of PPHN in infants with MAS gocytosis Æ resp dist ◦ anatomic abnormalities support may be persist for days or even x evidence of injury to the vascular bed of the lung that dates back several weeks prior to birth. x Vasc smooth muscle extends into the walls of normally non- muscularized intra-acinar arterioles Æ bad PPHN ◦ active vasoconstriction x directly or may cause plt aggregation Æ release of thromboxane, a potent pulm vasoconstrictor Avery 1991, Hansen and Corbet Fanaroff and Martin 2002, Miller, Fanaroff and Martin Avery 1991, Hansen and Corbet y coarse, irregular densities with areas of diminished aeration and consolidation y pneumomediastinum, PTX y cardiomegaly at times, due to perinatal y "salt and pepper" Left pneumothorax with depressed diaphragm and minimal mediastinal shift because of Air trapping and noncompliant lungs hyperexpansion from airway obstruction Dave Clark emedicine 2004 Dave Clark emedicine 2004 y let them breathe fast in hood oxygen ◦ arterial line – frequent ABGs Diffuse chemical ◦ minimal stimulation ◦ try to avoid intubation from constituents y if intubate – no longer aggressive in hyperventilation / alkalosis but avoid hypercarbia / acidosis ◦ if a lot of parenchymal disease Æ HFOV y target normal blood pressure ◦ avoid hypotension Æ PPHN y not a big fan of nasal CPAP ◦ just makes them mad y if intubate, use sedation generously ◦ may need paralysis (no data) y nothing on this slide has been well-studied Dave Clark emedicine 2004 y r/o sepsis but not automatic commitment y meconium may inhibit surf function Æ to a full course Abx role for exogenous surf y steroids are not recommended – y multicenter RCT of term infants with e esp ilure, 50% be changing….
MAS as primary dx Æ surf decr need for ECMO Fanaroff and Martin 2002, Miller, Fanaroff and Martin Lotze et al, (J P (J P diatr 1998;132:40 diatr 1998;132:40--7) Need for ECMO (%) y A multicenter (n = 44), randomized, double- blind, placebo-controlled trial was conducted.
y Infants > 2000g and > 36 wks, OI* 15-39, ◦ by diagnosis (MAS, sepsis, or idiopathic PPHN) and ◦ oxygenation index (15 - 22, 23 - 30, 31 - 39) y four doses of surfactant (Survanta) 100 mg/kg or air placebo, every 6 hours before ECMO treatment and four additional doses during ECMO, if ECMO was required. The need for ECMO therapy was significantly less in the surfactant group than in the placebo group (p = 0.038)

Need f r ECMO (%) this effect was greatest within the lowest oxygenation index stratum (15 to 22; p = 0.013).
Steroids in MAS - Cochrane Review - 2003 Steroid therapy for meconium aspiration syndrome in
newborn infants
Cochrane Reviews
Ward, M; Sinn, J
Date of Most Recent Update: 25-August-2003
esent, there is insufficient to assess the effe y in the management the management of meconium aspiration syndro aspiration syndr me. A large randomized randomized contro contr lled trial assessing lled trial assessing potential benefits potential benefits and harm w Modes of action to explain efficacy of y inhibition of prostaglandin and leukotriene y removal of excess edema fluid y suppression of cytokine ession of cytokine inflammatory reaction y inhibition of nitric oxide production y Sultantate of Omany pilot study, case series, not RCTy all ventilated, all OI >25, all PPHNy average age starting dex 80hrsy dex 0.5/kg/day div q12h x3d, 0.3 x3d, 0.125 x3dy steroids started if not weaning on vent or OI worsening over ◦ placebo◦ 0.5 mg/kg/d Methylprednisilone div q12h◦ 50 ug q12h budesonide y not sure if ventilated population y 2 deaths, both in placebo group (one with massive PTX, one with sepsis/DIC) y no baby in steroids group needed MV y RCT, n=99, 3 arms, not blindedy placebo, methylprednisilone 0.5mg/kg/d q12h x7d, budesonide 50ug q12h x7d y Need larger studies y Need long term follow up ◦ Effects on brain / neurodevelopment x Need really large studies y Could be useful for sickest babies Inflammation in MAS y 11 neonatal patients with MAS, 16 neonates without MAS, and 9 healthy children.
y Tripathi et al, Ind J Med Microbiology (2007) 25 y 6 cytokines higher in MAS compared with non-MAS ◦ IL-6, IL-8, GM-CSF, G-CSF, interferonγ, MIP-1, and TNF y RCT, blinded, 3 groups y IL-10 (anti-inflammatory cytokine) also was higher in ◦ Placebo, methylprednisilone, inhaled budesonide x Steroids given for 7 days ◦ Tracheal aspirates on day 1, 3, 4 y Decreased TNFα in steroid treated groups y TNFα levels correlated with LOS meconium aspiration syndrome y 25,000-30,000 cases per year in US ◦ 1000 deaths annually Gelfand, J Fanaroff, Walsh, Clinics in Perinat2004;31,445-452 y 13% of live births have MSAF y 5% of these babies have MAS • Amnioinfusion y MAS defined as "resp distress in an • intrapartum suctioning infant born through MSAF whose • tracheal suctioning symptoms cannot be otherwise explained" Gelfand, J Fanaroff, Walsh, Clinics in Perinat 2004;31,445-452 Fraser WD et al, N Engl J Med 2005;353: 909-17Average BW 3.4 kg y dilutes meconiumy relieves cord compression Æ relieving hypoxia Æ decreasing gasping y does it reduce MAS? – meta-analysis of 13 studies suggests that both fetal distr ss and MAS x Hofmeyr, GJ et al, Cochrane review, 2001, 2004 Gelfand, J Fanaroff, Walsh, Clinics in Perinat 2004;31,445-452 Table 3 continued…
Amnioinfusion –– Fraser WD et al
E gl J Med 2005;353:
gl J Med 2005;353: 909
y Conclusions: For women in labor who have thick MSAF, amnioinfusion did not reduce the risk of moderate or severe meconium aspiration s yndrome, perinatal death, or other major maternal or neonatal disorders.
DeLee and tracheal suctioning y preventive approach ◦ thorough suctioning of nose and pharynx by OB after delivery of head but before thorax is delivered and the infant can take a breath ◦ if infant depressed Æ tracheal suctioning to remove residual mec Amnioinfusion does not prevent meconium aspiration syndrome. ACOG Committee Opinion No. 346.
American College of Obstetricians and Gynecologists. Obstet Gynecol 2006;108:1053–5.
Fanaroff and Martin 2002, Miller, Fanaroff and Martin Intra artum suctioning y considered standard for 25 years x Carson et al Am J Ob Gyn 1976;126:712-5 y Wiswell et al Peds 2000;105:1-7 y to examine tracheal suctioning - ◦ MAS increased in those who did not receive intrapartum oropharyngeal suctioning before Fanaroff and Martin delivery of the shoulders (8.5% vs. 2.7%, OR 3.35, CI 1.55-7.27) Miller, Fanaroff and Martin Gelfand, J Fanaroff, Walsh, Clinics in Perinat 2004;31,445-452 tum Suctioning
tum Suctioning –– NRP
y Aspiration of meconium before delivery, during birth, or during resuscitation can cause severe aspiration pneumonia. y One obstetrical technique to try to decrease aspiration has been to suction meconium from the infant's airway after delivery of the head but before delivery of the shoulders y Although some studies (LOE 3) suggested that intrapartum suctioning might be effective for decreasing the risk of aspiration syndrome, subsequent evidence from a large multicenter randomized trial (LOE 1) did not show such an y Therefore, current recommendations no longer advise routine intrapartum oropharyngeal and nasopharyngeal suctioning for infants born to mothers with meconium staining of amniotic fluid (Class I). evidence documented only short-term benefits from the therapy or when positive results were documented with lower levels of y Class IIb recommendations fall into 2 categories: ◦ (1) optional and ◦ (2) recommended by the experts despite the absence of high-level supporting evidence. ◦ Optional interventions are identified by terms such as "can be considered" or "may be useful." Interventions that the experts believe should be carried out are identified with terms such as "we Vain et al, Lancet 2004;364;597-602 Intra artum suctioning y Infants were randomly allocated to either suctioning of the oropharynx and nasopharynx (including the hypopharynx) before delivery of the shoulders (suction group), or no suctioning (no-suction group).
y 10-Fr to 13-Fr connected to a negative pressure of y Oropharyngeal suctioning was done first, followed by bilateral nasopharyngeal suctioning, when possible.
y Thereafter, care was given according to NRP ◦ tracheal suctioning for non-vigorous infants Vain et al, Lancet 2004;364;597-602 Vain et al, Lancet 2004;364;597-602 Intra artum suctioning y The primary outcome was incidence of MAS.
y Diagnosis of the syndrome was defined by (1) respiratory distress (tachypnea, retractions, or grunting) in a neonate born through MSAF; (2) saturation levels at 92% or greater; (3) oxygen requirements starting during the first 2 h of life and lasting for 12 h or longer; and (4) absence of congenital malformation of the airway, lung, or heart. Vain et al, Lancet 2004;364;597-602 Vain et al, Lancet 2004;364;597-602 DeLee and tracheal suctioning y preventive approach ◦ thorough suctioning of nose and pharynx by OB after delivery of head but before thorax is delivered and the infant can take a breath ◦ if infant depressed Æ tracheal suctioning to remove residual mec Fanaroff and Martin 2002, Miller, Fanaroff and Martin Fanaroff and Martin 2002, Miller, Fanaroff and Martin T acheal Suctioning
acheal Suctioning –– NRP
y Traditional teaching recommended that meconium- stained infants have endotracheal intubation immediately following birth and that suction be applied to the endotracheal tube as it is withdrawn. y Randomized controlled trials have shown that this off rs no benefit if I). A vigorous infant is defined as one who has strong respiratory efforts, good muscle tone, and a heart rate 100 beats per minute (bpm). y Endotracheal suctioning for infants who are not vigorous should be performed immediately after birth Endotracheal intubation at
acheal intubation at
T acheal suctioning mor idity and mor
idity and
tality in vig
tality in
us, meconium
stained infants bor
infants bor at term
y Linder et al – Israel – J Peds 1988 – n>500 y Halliday, HL; Sweet, D; Cochrane review, 2000, 2005 ◦ no morbidity in infants with Apgar scores of 8 or higher at 1 minute who had been deLee suctioned y 4 RCTs y Meta-analysis of these trials does not support routine y Wiswell et al Peds 2000;105:1-7 use of endotracheal intubation at birth in vigorous ◦ prospective RCT of vigorous infants with MSAF meconium-stained babies to reduce mortality, MAS, s symptoms / disor O2 need ,stridor ◦ 149 (7.1%) of enrolled infants Æ resp distress HIE and convulsions. x 62 (3%) dx with MAS y Conclusions: Routine endotracheal intubation at birth in vigorous term meconium-stained babies has not been x 87 (4.2%) other (TTN, delayed transition, sepsis, PPHN) shown to be superior to routine resuscitation including no diff whether tracheal y suctioned or not x MAS 3.2% intubated vs. 2.7% non-intubated ◦ no diff in other resp disorders y This procedure cannot be recommended for vigorous infants until more research is available.
co um Aspi
Dargaville, Morley et al, Melbourne, AJRCCM 2003; 168:456–463 actant La
actant La g
hn P Kinsella,
y commentaryy method to enhance removal of particulate meconium from the airway using bronchoalveolar lavage with a dilute bovine surfactant preparation. dilute surf lavage y 2 week old pigletsy They found that a 30-ml/kg lavage volume of dilute surfactant was associated with increased meconium removal, improved post-lavage lung function, and less lung injury as compared with perflourocarbon emulsion or multiple, smaller aliquots of dilute surfactant.
dilute surf lavage a eutic lung
peutic lung lava
in meconium
syndr me:
e: A preliminar
y Dargaville, Morley et al (Australia) ◦ Journal of Paediatrics and Child Health 43 (2007) 539–545 y Infants with severe MAS, HFOV y Lavaged infants typically stablized but not improving, still on high FiO2 with an alveolar-arterial oxygen difference (AaDO2) of >400 mm Hg if arterial pH < 7 sat < 75% ,or mea ◦ Lavage performed in sedated muscle-relaxed infants y 1/5 dilution of Survanta, mixed gently in sterile NS and warmed to 37°C, delivered via catheter protruding approximately 0.5 cm below ETT y Lavage aliquot volumes were increased through the case series, aiming to deliver two aliquots of 15 mL/kg 3-5 minutes apart Dargaville, Morley et al, Melbourne, AJRCCM 2003; 168:456–463 Surfactant
factant lava
y 8 babies enrolled ◦ median age of 23 h (range 8–83 h)◦ 88% nitric oxide, 3 on adrenalin infusion ◦ lavage was associated with significant all lavaged infants y 3 in "Therapeutic lavage group"Æ subgroup P=0.03 repeated measures ANOVA of infants who received at least 25mL/kg y 34 babies in non-lavaged group ◦ Comparable, if anything, lavaged babies sicker Surfactant
factant lava
◦ efficacy deserves further investigation in a randomized controlled trial y About 10 prior human studies y RCT – Surfaxin ongo y less post-term pregnancies y Lavage with Exogenous Surf Suspension in MAS Gelfand, J Fanaroff, Walsh, Clinics in Perinat 2004;31,445-452 Use of Neonatal
Extracorpor al Membrane
enation E
CMO) How Ne
T eatment Modalities
cte ECMO Utilization
Patients were included if:
*OI >15 x 1 within the first 72 hours
of admission
◦ >35 weeks
dx MAS, PPHN or sepsis/pneumonia
<5 days of age on admission
Pre-ECMO surfactant 3 (6.1%)iNO Hintz S et al, Pediatrics 2000;106:1339– 1343
Hintz S et al, Pediatrics 2000;106:1339– 1343
Neonatal Respiratory ECMO Neonatal Respiratory ECMO Conrad SA et al, ASAIO Journal 2005;51:4-10 Conrad SA et al, ASAIO Journal 2005;51:4-10 From the Departments of Pediatrics and Obstetrics/Gynecology, Wilford Hall Medical Center, Lackland AFB, Texas Obstet Gynecol 2002;99:731–9 CONCLUSION: Reduction in post-term
delivery was the most important factor in
reducing meconium aspiration syndrome.

Yoder et al, Obstet Gynecol 2002;99:731–9 Yoder et al, Obstet Gynecol 2002;99:731–9 Yoder et al, Obstet Gynecol 2002;99:731–9 Yoder et al, Obstet Gynecol 2002;99:731–9 Yoder et al, Obstet Gynecol 2002;99:731–9 Yoder et al, Obstet Gynecol 2002;99:731–9 Yoder et al, Obstet Gynecol 2002;99:731–9 ◦ 1061of 2,490,862 live births (0.43 of 1000)◦ decrease in incidence from 1995 to 2002 ◦ 34% > 40 weeks' gestation ◦ 6.5% > 41 weeks' gestation Data were gathered on all of the infants in Australia and New Zealand who y total birth population were intubated and mechanically ventilated with a primary diagnosis of ◦ 16% > 40 weeks' gestation MAS between 1995 and 2002, inclusive. Information on all of the live births ◦ 2.0% > 41 weeks' gestation during the same time period was obtained from perinatal data registries.
y P < .001 in both cases y Associated with MASINT: ◦ low 5-minute Apgar score MASINT = intubated for MAS ◦ maternal ethnicity Pacific Islander or indigenous Australian◦ planned home birth y Compared with 1995, in 2002, there were fewer deliveries beyond 41 weeks' gestation (1.6% vs 2.8%; P .001) and y fewer infants with a 5-minute Apgar score <7 (1.4% vs 1.7% y These factors combined account for 62% of the reduction in MAS incidence noted in this time period.
Is there a trade-off? Logistic regression Æ5 factors independently related to resp morbidity:GA, C/S, male, FHR, low 5 min Apgar Change in GA distribution from 1990 to 1998 Yoder et al, Ob Gyn March 2008 y MSAF is often associated with in utero fetal distress and y The pathophysiology of MAS includes airway obstruction, surfactant inactivation and a chemical pneumonitis leading to air trapping, atelectasis and PPHN.
y Standard therapy for MAS includes supplemental oxygen, y The use of ECMO for MAS-PPHN patients is decreasing due to the increased use of other therapies such as HFV, surfactant and iNO.
y Preventive measures such as amnioinfusion, intrapartum oro- and naso-phayngeal suctioning, and tracheal suctioning are now controversial and no longer recommended as routine.
y The incidence of MAS is decreasing, primarily related to fewer post-mature infants and less intrapartum fetal distress.



Open Journal ofClinical & Medical Volume 2 (2016) Issue 11 Case Reports Low-Resolution Electromagnetic Tomography (LORETA) of changed Brain Function Provoked by Pro-Dopamine Regulator (KB220z) in one Adult ADHD case Bruce Steinberg; Kenneth Blum*; Thomas McLaughlin; Joel Lubar; Marcelo Febo; Eric R. Braverman; Rajendra D Badgaiyan

Healthcare marketing 07/2014

Die Inspirato Pharma Marketing Awards wurden am 2. Juni 2014 in Frankfurt verliehen Quelle: Pharma Marketing 2014 - www Preise für OTC-Marketing verliehen Der Inspirato Pharma Marketing Award kürt zum zweiten Mal Unternehmen, Marken und Neueinführungen aus dem OTC-Markt. Zu den Gewinnern in die-sem Jahr gehören die Firma Bionorica, die Marke Sinupret und das Neuprodukt Voltaren Schmerzgel forte.