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CHAIR OF PEDIATRY WITH MEDICAL GENETICS SUBJECT OF LECTURE: “Pneumonias of newborns. Hemorrhagic disease of newborns”. Definition Pneumonia is an acute infectious disease of the pulmonary parenchyma, that is diagnosed in case of presence of breathing violation syndrome, physical data and infiltrative changes at roentgenogram. Variant of pneumonia Depending on period of infection: Intrauterine transplacental (causative agent entered from mother through placenta) and antenatal (causative agent penetrates fetus through amniotic fluid); Intranatal (child is infected during delivery through infected maternal passages); Postnatal (infection happens after birth): hospital; “street”, “home”, acquired pneumonias (out of hospital); children have ventilation associated pneumonias at the first 72 hours of being on artificial pulmonary ventilation. Pneumonias etiology Intrauterine pneumonias: streptococcus of В, G and D groups, Кl. pneumoniae, St. aureus, Listeria monocytogenes, E.coli. Out of hospital pneumonias: Staphilococcus aureus, Streptococcus epidermidis, Str. Рneumoniae, Chlamidia pneumoniae, Mycoplasma pneumoniae, Hospital pneumonias: Pseudomonas aeruginosa, Кl. pneumoniae, E. coli, Proteus spp., St. aureus, anaerobic flora – Acinetobacter, Serratia. Ventilation associated pneumonias: pneumococcus, Hem. Influenzae.. Risk factors of pneumonia development at newborns Somatic and/or obstetric pathology during pregnancy (it causes chronic antenatal hypoxia of fetus and suppression immunologic reactivity). Mother’s chronic infection pathology (especially of urogenital system). Acute infectious diseases during pregnancy. Complications of intranatal period (choreoamnionitis, premature membranes rupture, long waterless period, plural manual researches). Pneumopathies. Congenital violations of lungs development. Susceptibility to regurgitates. Prematurity, intrauterine growth retardation. Pathogenesis Passes of lungs contamination by the pathogenic flora: Bronchogenic-droplet pass is typical for postnatal pneumonia and pass through infected amniotic fluid is typical for intranatal pneumonia; microaspiration of oral pharynx content; Hematogenic – causative agent entering from extrapulmonary infection source; Lymphogenic – infection spread from the nearby organs. Pathogenic phases: Entering of the causative agent to the pulmonary tissue, hydropic – inflammatory obstruction of respiratory tract, function violations of ciliated epithelium with spread of the agent through tracheobronchial tree to alveoles and between alveoles through Kon’s pores; Primary alteration of pulmonary tissue with development of morphologic substrate of pneumonia (of the focus, segment, lobe or intersticium ); Activation of processes of lipid peroxidation with damaging not only causative agent but also structures of own organism, function violations of surfactant, destabilization of cell membranes –increase in size of the injured pulmonary tissue; Pathogenesis Pathogenic phases (continue): Violation of perfusion through alveole – capillary membrane – respiratory hypoxia, development of complex dyspnea, tachycardia, increase of stroke volume (SV), cardiac output (CO); As a result of hypoxia the increase of pressure in the system of pulmonary artery causes overload of right heart, dystrophic changes in myocardium – circulatory hypoxia; Respiratory and circulatory hypoxia cause centralization of blood circulation and violation of perfusion of peripheric tissues, that causes accumulation of suboxides, acidosis and hystotoxic hypoxia development; In condition of acidosis О2-connecting function of erythrocytes is violated - hemic hypoxia. Toxicosis appears: exogenous – as a result of action of microbal toxins, and endogenous – as a result of metabolism violations. Violations of other organs and systems, all types of exchange and immunologic homeostasis appear. Brain is mostly sensitive to hypoxemia and hypoxia, that’s why function violations of CNS are irreplaceable concomitants of newborns. Classification By the periods of origin: intrauterine (antenatal and transplacental), intranatal, postnatal (by the location of origin: out-of-hospital, hospital). By the etiology: viral, bacterial, fungous, mixed. By the morphologic substrate: focal, segmental, lobal (croupous), interstitial. By the localization: one-side, two-side, injured lobe and segment. By the course: acute (till 6 weeks), prolonged. By the severity: moderate, severe, over severe. By the degree of respiratory insufficiency: І, ІІ, ІІІ degrees. By the period: starting, height, resolution, recovery. By the presence of complications: Toxic (cardio- vascular syndrome, syndrome of neurotoxicosis, DICsyndrome, gastric- intestinal syndrome, acute epinephros insufficiency). Purulent: pulmonary (abscess, destruction), pulmonary- pleural (pleuritis, pneumothorax), extrapulmonary (meningitis, osteomielitis, pyelonephritis, otitis). Examples of diagnosis: Antenatal interstitial pneumonia, severe form, acute course, starting period, uncomplicated, RI of the third degree Intranatal small- focal bronchopneumonia, medium difficult, acute course, period of height, uncomplicated, RI of the second degree Clinical and diagnostic criteria of pneumonia Pulmonary (respiratory) complaints Intoxication symptoms Signs of respiratory insufficiency Local physical data Roentgenologic changes Laboratory data Clinical and diagnostic criteria of antenatal pneumonia Symptoms of respiratory insufficiency (dyspnea, tachypnea, dilated nostrils, additional muscles’ part in the act of breathing, cyanosis, expiratory sounds) are shown up in the first minutes of life. Often it connects with difficult hypoxia and it is one of the component of generalized intrauterine infection. Intoxication symptoms (depression, temperature instability, appetite decreases, tolerance to enteral feeding decreases, haemodynamics violations, jaundice, haemorrhagic symptom, tachycardia, deafness of heart sounds) prevail in clinic. Physical data is informative: dullness on percussion, small- vesicle and crackling rales during inspiration. Clinical and diagnostic criteria of intranatal pneumonia Light interval is typical (2-3 days of life); Often it connects with purulent conjunctivitis and local purulent skin injures; Physical data is informative: dullness on percussion, small- vesicle and crackling rales during inspiration. Clinical and diagnostic criteria of postnatal pneumonia Out-of-hospital: The beginning is acute, it starts with catarrhal processes in epipharynx, temperature increase with consequential RI. Processes of toxicosis prevail at the beginning of disease (flaccidity, refusal of food, decrease of muscle tonus). Physical data of lungs are small informative: tympanic resonance at periapical areas, rales are rare. Hospital: Difference between hospital and out-of-hospital pneumonias is: spectrum of causative agents, resistance of agents to antibacterial therapy, difficulty and frequency of complications, high lethality. Features of pneumonia course at premature children: Dominating of symptoms of RI and toxicosis in clinics. Fever is not constant, it also can be hypothermia. The frequency of complications is high: pulmonary (pneumothorax, atelectasis , pleuritis) and extrapulmonary (otitis, enteroparesis, haemorrhagic symptom, metabolic violations- mixed acidosis, hypoglycemia, hypo-calcium, sodium, - potassiumemia, hyperbilirubinemia). Aspiration pneumonia is more frequent at premature children in comparison with mature ones. The following order is characteristic: RDS – pneumonia- sepsis, as opposed to mature children that in case of sepsis don’t have lungs as site of entry of infection. The frequency of connecting with other diseases is high. The frequency of remote consequences is high, it causes recidivation of bronchopulmonary diseases. Plan of examination of the newborn with suspicion on pneumonia Roentgenography of chest in 2 projections (interspersed peribronchial focal infiltration or focal shadows at the background of increased bronchovascular pattern and hyperpneumotization). Clinical blood analysis with calculating of thrombocytes (leucopenia or leucocytosis are typical, increase of total amount of stab neutrophils, leukogram shift to the left, total neutrophillosis, increase of leucocytic index, thrombocytopenia). Determination of gas content of blood and indices of acid-base balance. Virologic and bacteriological research. Blood examination on its sterility. Urine clinical analysis. Cerebrospinal puncture by indications.. Treatment of pneumonias at newborns Main directions of therapy: Keeping the therapy- protective, hygiene and sanitary regimen. Infusion therapy. Treatment of respiratory insufficiency. Etiotropic therapy. Pathogenic therapy (anticoagulant and antienzyme therapy). Increase of child’s resistance (immunesubstitutive and vitamins therapy). Physical therapy and exercise therapy. Treatment of pneumonias at newborns Volume and type of feeding is determined by age, maturity and condition of the newborn. Indication for enteral feeding: -absence of vomiting and regurgitations; -absence of bloating; -absence of decompensation of circulation and RI II- III degrees. Purpose of infusion therapy is: absorption of toxins and its excretion from the organism, correction of acid-base balance violations and water-electrolytes exchange violations, improve of rheological properties of blood. The fluid volume is counted individually and it depends on daily needs in fluid, condition of heartvascular system, signs of dehydration, presence or absence of pathologic loss. Treatment of pneumonias at newborns Solutions that are used for infusions: 10% solution of glucose, 5% solution of albumin, fresh frozen plasma. The fluid is injected through infusator droply. Features of infusion therapy: Using of osmose diuretics and volemic preparations is forbidden (10% solution of albumin, reopolyglycin). 5% albumin can be used not often than 1 time a day. Infusion therapy is carrying under obligatory control by the hour diuresis and water-saline balance. Using the lazix by 1mg/kg 2 times a day is obligate. Plasmapheresis and hemosorption can be used for detoxication. Treatment of pneumonias at newborns Methods of oxygen therapy in case of pneumonia Through mask or funnel – speed of oxygen giving is 2-3 l/min., it allows to make oxygen concentration around 25-34%. Through oxygen tent – speed of oxygen giving is 3-4 l/min., it allows to make oxygen concentration around 25-40%. Through the nasal cannulas (“moustache”) – speed of oxygen giving is 0,2-0,5 l/min., it allows to make oxygen concentration around 40-50%. Oxygen therapy that is carrying directly in the baby’s place – speed of oxygen giving is 3-4 l/min., it allows to make oxygen concentration around 30%. An indispensable condition of oxygen therapy is warming-up and humidification of oxygen. Treatment of pneumonias at newborns Indications for spontaneous breathing under permanent positive pressure (SBUPPP) : augmenting of RI symptoms on the background of usage of oxygen therapy by free oxygen flow, rating by the Silverman’s or Down’s scale is > 4 points, frequent and long attack of apnea, bradycardia. Indications for artificial lung ventilation (ALV): clinical symptoms of severe RI (rating by the Silverman’s or Down’s scale is > 7 points), on the background of SBUPPP Ра О2 is <50 mm. mercury column, Ра СО2 is >60 mm. mercury column, рН is <7.2; shock, prolonged apnea with bradycardia and cyanosis; persistent central cyanosis on the background of SBUPPP arterial hypotension; violations of the peripheral haemodynamics. Inhalation therapy (lazolvan, euphylin, hydrocortizon, vit C, 2% solution of chlorides or hydrocarbonate of sodium), ultrasonic inhalator is used. Treatment of pneumonias at newborns Treatment of intrauterine pneumonia: 1. Penicillins: Natural – benzylpenicillin by 25 000 UA/kg/day 2 times parenteraly; Semisynthetic: - ampicillin, oxacillin by 25 mg/kg/day 2 times parenteraly; - amoxicillin by 30 mg/kg/day 2 times parenteraly; - “protected” penicillins (amoxyclav, ampysulbin) - 30 mg/kg/day 2 times parenteraly. 2. Cephalosporins of the І generation (cephalexin, cephazolin) or ІІ generation (cephuroxim) by 20-50 mg/kg/day 2 times parenteraly. 3. Aminoglycosides of the ІІ generation (gentamycin) or the III generation (amicacyn) by 5-7,5 mg/kg/day 2 times parenteraly. Treatment of pneumonias at newborns Treatment of out-of-hospital pneumonia: 1. Amoxyclav - 30 mg/kg/day 2 times parenteraly; 2. Cephuroxim - 50 mg/kg/day 3 times parenteraly. 3. Aminoglycosides of the ІІ generation (gentamycin) or the III generation (amicacyn) by 5-7,5 mg/kg/day 2 times parenteraly. Penicillins and cephalosporins are effective at treatment of out-of-hospital pneumonia that are caused by Str. рneumoniae, H.influenzae, at pneumonia that are caused by Chlamidia pneumoniae, Mycoplasma pneumoniae macrolides should be used (erythromycin, azitromycin – 10 mg/kg/day by the scheme). Treatment of pneumonias at newborns Treatment of hospital pneumonia: 1. Semisynthetic penicillins: carbopenicillins (carbenicillin) by 100 mg/kg/day, ureidopenicillins (azlocillin, mezlocillin) by 50 mg/kg/day, “protected” penicillins (amoxiclav) by 30 mg/kg/day. 2. Cephalosporins of the IIІ generation (cephtriaxon, cephoperazon, cephotaxim) or the IV generation (cephepim) by 50 mg/kg/day. 3. Aminoglycosides of the ІІ generation (gentamycin, tobramycin, sizomycin by 4-8 mg/kg/day or the III generation (amycacin by 7,5 mg/kg/day, nethilmycin by 2,5 mg/kg/day). 4. Fluoroquinolones of the II (ciprofloxacin), the III (levofloxacin) or the IV generation (gatifloxacin) by 15 mg/kg/day in 2 doses. 5. Carbopenems (imipenem, meropenem) by 60 mg/kg/day. The 4th and the 5th groups of antibiotics are prescribed according to live indications. Haemorrhagic disease of newborns. Definition Haemorrhagic disease of newborns (HmDN) is a disease of newborns that is connected with the low rate of vit Kassociated factors of blood coagulation. At the first days of life healthy mature newborns have the low rate of vit K- associated factors of blood coagulation, that is caused not by vit K deficiency, but it is caused by transient insufficiency of liver function. 2-5% of children have more low level of vit K- associated factors of blood coagulation in comparison with healthy mature children, and exactly they have HmDN. Variants of HmDN Early HmDN. It develops at the first day of life. It occurs rarely. Clinically it is characterized by skin and mucous layers hemorrhages, intracranial hemorrhages, hemorrhage from the umbilical wound, melena (intestinal hemorrhage). Risk factors: applying medical therapy (anticoagulants, anticonvulsant preparations, antibiotics, sulfanilamides, acetylsalicylic acid) at the late periods of pregnancy. Classical HmDN. It develops at the 2nd- 6th day of life. Clinically it is characterized by melena, skin and mucous layers hemorrhages, hemorrhage from the umbilical wound. Risk factors: gestosis of pregnancy, deficiency of vegetables in the feeding of pregnant woman, liver diseases, bile-excreting pass diseases, intestinal disbacteriosis, prematurity, intrauterine growth retardation. Late HmDN. It develops after the 1st week of life during 3-8 weeks. Clinically it is characterized by intracranial hemorrhages, skin hemorrhagic syndrome, melena. Risk factors: artificial feeding, absence of prophylaxys prescription of vit K. Diagnostics and treatment of HmDN Diagnostics is based on anamnesis and typical clinical data. Among laboratory methods test of Apt is used. Also prolongation of prothrombin time and shortening of prothrombin index are typical. Treatment: Treatment- protected regimen; Adequate feeding; Prophylactical intramuscularly injection of vit K (1% solution of vicasol by 0,3-0,5 ml 1-2 mg) after birth; Local therapy in case of melena is 0,5% of sodium chlorides per os by 1 tea spoon 3 times a day, solution of thrombin in epsilonaminocapron acid per os by 1 tea spoon 3 times a day. In case of difficult course using of fresh frozen plasma by 15 ml/kg and concentrate of factors of prothrombin complex PPSB by 15-30 UA/kg is possible.