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Clinical Hospital Centre Zagreb, Department of Obstetrics and Gynecology,** DIGOXIN AND AMIODARON
IN FETAL SUSTAINED SUPRAVENTRICULAR TACHYCARDIA
AND NONIMMUNE HYDROPS
DIGOXIN I AMIODARON
KOD TRAJNE FETALNE SUPRAVENTRIKULARNE TAHIKARDIJE
I NEIMUNOLO[KOG FETALNOG HIDROPSA
Vesna Sokol,** Josip Juras,* Ivan Mal~i},*** Jozo Blaji},** Marina Ivani{evi}**
Key words: fetalus, tachycardia supraventricular, fetal hydrops, digoxin, amiodarone
SUMMARY. Supraventricular tachycardia is the most common and clinically significant form of sustained fetal tachyar-
rhythmia in pregnancy; depending on duration and high rate variability heart failure and nonimmune hydrops may de-
velop which are associated with a high incidence of perinatal mortality. Doppler/echo diagnosis is usually accidental
during second and third trimester of pregnancy. Therapeutic goals are cardioconversion to sinus rhythm and recovery of
heart failure. We present a case of fetal supraventricualr tachycardia diagnosed at 29 weeks of gestation with nonimmune
hydrops. Treatment with digoxin and amiodarone was successful. The heart rate restored to sinus rhythm and nonim-
mune hydrops resolved within three weeks of treatment. Therapy with two drugs that act synergistically may be more
efficient than monotherapy in blocking likely atrio-ventricular reentry mechanism by accessory pathway in sustained
supraventricular tachycardia, thus allowing resolution of hydrops with favorable management outcome.
Klju~ne rije~i: fetus, tahikardija supraventrikularna, fetalni hidrops, digoksin, amiodaron
SA`ETAK. Supraventrikularna tahikardija je naj~e{}i i klini~ki najzna~ajniji oblik fetalne tahiaritmije u trudno}i, a ovi-
sno o trajanju i visini sr~ane aktivnosti mogu se razviti zatajenje srca i neimuni fetalni hidrops, oboje povezani s lo{im
perinatalnim ishodom. Tijekom drugog i tre}eg tromjese~ja dijagnoza se ~esto slu~ajno postavlja ultrazvu~nim dopler-
skim nalazom. Terapijski cilj je konverzija u sinus ritam i oporavak sr~ane funkcije. Donosimo prikaz slu~aja fetalne
supraventrikularne tahikardije s neimunim hidropsom, dijagnosticirane u 29. tjednu trudno}e. Terapija digoksinom i
amiodaronom bila je uspje{na. Ponovo je uspostavljen sinusni ritam sr~ane frekvencije, a neimuni hidrops se povukao
unutar tri tjedna lije~enja. Terapija dvama lijekovima sa sinergisti~kim djelovanjem mo`e biti u~inkovitija od monotera-
pije u blokiranju vjerojatno ponovnog ulaska atrio-ventrikularnog impulsa pomo}u sporednog puta u supraventrikular-
noj tahikardiji, time dopu{taju}i povla~enje hidropsa te bolji ishod.
Introduction
with minimal pericardial effusion. There was no history of fever or thyrotoxicosis. In family history, her mother Supraventricular tachycardia is the most common and has angina pectoris and arterial hypertension. The pa- clinically significant form of sustained fetal tachyar- tient was admitted to our hospital for administration of rhythmia in pregnancy. Depending on duration and high antiarrhythmic therapy. At admission patient’s height rate variability, heart failure and nonimmune hydrops was 168 cms and weight 73(+9) kg. Blood pressure was may develop, that are associated with a high incidence 110/60 mmHg. ECG: sinus rhythm with 76 bpm.
of perinatal mortality. Therapeutic goals are cardiocon-version to sinus rhythm and recovery of heart failure, Fetal echocardiography showed normal heart posi- most frequently by digoxin and sotalol.
tion in left hemithorax with higher cardiothoracic index of 0.42 (normal 0.25–0.35), enlarged heart silhouette Case report
underlying both dilated atria with normal ventricles and valvular morphology, normal atrioventricular concord- A 28 year old primigravida at 29 weeks of gestation ance and relations to surrounding internal organs. Pul- (with ultrasound analysis the pregnancy was 2 weeks monary veins and vv.cavae were of normal anatomy and younger) was referred to our antenatal clinic because of inflow. Patent foramen ovale with r-l shunt and ductus fetal tachycardia detected during her routine antenatal Botalli with communications between pulmonary artery scan. She was transferred from another clinical hospital and aorta corresponded with the mildly decreased same where she was treated with sotalol on which she devel- pressures in both pulmonal artery and aorta of 0.4m/s oped allergic reaction. Her antenatal period was une- (normal 0.6–07m/s). Doppler/M-mode echocardiogra- ventful till 26 weeks when Doppler/M-echocardiogra- phy demonstrated paroxysms of SVT in the range of phy showed fetal supraventricular tachycardia (SVT) 237–260 beats per minute intermittently falling down to Sokol V. et al. Digoxin and amiodaron in fetal sustained supraventricular tachycardia and nonimmune hydrops 131 beats per minute, but only rare and transitory. There There are three different types of fetal arrhythmias that can be seen in pregnancy such as fetal tachycardia The patient was started on digoxin 3×0.5 mg i.v. per with baseline fetal heart rate over 160/min (SVT, atrial day for three days and continued 3×0.5 mg per os daily. flutter or fibrillation, ventricular tachycardia), fetal bra- During complete treatment, serum electrolytes and elec- dycardia with baseline heart rate less than 110/min., trocardiography were monitored. Three days after ini- and the most common, premature beats as atrial and tial therapy with digoxin the patient developed symp- ventricular extrasystoles. An initiating premature beat toms of digoxin toxicity with epigastric pain, vomiting caused by abnormal automaticity can precipitate an epi- and nausea and ECG–changes showed intermittent first sode of SVT sustained by AV reentry mechanism and degree and second degree Mobitz II AV block and ST accessory pathway with AV conduction 1:1 up to 220 to denivelation. Serum digoxin levels were elevated up to 260 bpm (accounts for 93% of total SVT with 1:1 AV 5.3 mmol/L (normal 0.7–2.5 mmol/L). Fetal heart rate conduction).3,4 It is the most commonly encountered fe- was found to be normal. She stopped taking digoxin tal cardiac arrhythmia in pregnancy that may be associ- three days till clinical and ECG normalization and after ated with adverse perinatal outcome if untreated.5 Fetal that she again continued digoxin treatment in dose 3×0.5 SVT can be presented like non sustained (tachycardia mg per os daily with expected maintenance dose (serum with intermittent sinus rhythm) and sustained (pro- range 2.0–2.5 mmol/L). Fetal heart rate was found to be longed uninterrupted tachycardia of >12h), which is he- between 214–129/min with prevalence of tachycardia. modynamically more dangerous for fetal life.4 In this Two weeks later Doppler/M-echocardiography showed case, sustained SVT with 1:1 atrioventricular conduc- the signs of fetal hydrops, the most probable because of tion was diagnosed prenatally by the presence of 1:1 underlying heart decompensation. As there were no atrioventricular contraction sequence during tachycar- signs of maternal digoxin intoxication and fetal heart dia, abrupt onset and terminations with minimal heart rate was still high and unstable, amiodarone in a dose of rate variability. Our patient was without favorite risk 3×200 mgs was added as second line therapy. The dose factors for development of arrhythmia like smoking, of digoxin was reduced to 2×0.10 mg per day and amio- caffeine and illicit drugs. Fetal Doppler/M-echocardi- darone, after one week of therapy was gradually reduced ography showed structurally normal heart with only to 2×200 mg per day without any adverse effects. Fetal mildly enlarged cardiac silhouette and both atria.
cardiac decompensation and fetal hydrops disappeared In addition, there are some newer methods used today three weeks after starting antiarrhythmic drugs. The fe- for the diagnosis of SVT such as magnetocardiogram tal heart rate remained stable at 120–140 bpm till deliv- (MCG) and Doppler myocardial deformation analy- ery with only a few exacerbations. Last fetal ultrasound showed breech presentation. Patient’s autoimmune The prognosis and treatment of this kind of arrhyth- workup and TORCH screening were negative. Her thy- mia depend on the presence or absence of fetal hemody- namic compromise, gestational age of fetus at which the At 38 week and 6 days of gestation (on ultrasound tachycardia occurs, the ventricular rate, the percentage 36+6 weeks) she underwent elective cesarean section. of the time that the tachycardia is present and the site of The 2920 gs male infant with Apgar score 10/10 was origin of the tachycardia.5,8 Spontaneous resolution of delivered. The baby boy was transferred to Clinic of ne- SVT has been reported in some cases to occur in utero onatology for further observation. On second day of or later, during neonatal period.9,10 In fetus with a nor- hospitalization, the baby boy developed RDS, which mal anatomical survey, the management depends upon was treated with oxygen and i.v. antibiotics with gradu- the gestational age and the presence or absence of hy- al respiratory improvement. During hospitalization ba- drops. In our case we demonstrated nonimmune hy- by’s heart was monitored and was treated with digoxin drops fetalis secondary to sustained SVT that appeared 2 weeks after its initiation to develop heart failure from multiple episodes of tachycardia and recurring at rela- Discussion
The most important goal of treatment is the preven- Cardiac arrhythmias develop from impairment of im- tion or resolution of hemodynamic compromise. Today, pulse generation, impulse conduction or both. It is, numerous antiarrhythmic drugs have been prescribed however, difficult to establish the exact mechanism for for the treatment of fetal tachycardia as digoxin, sotalol, many clinical arrhythmias that can appear as response amiodarone and flecainide. We began the treatment to ischemia, inflammation, electrolyte disturbances, al- transplacentally with digoxin which is the drug of first tered load states, structural heart defects, inherited ge- choice for the treatment of SVT and two weeks later in netic conditions and other causes.1 Approximately 1% the sense of developing hydrops phenomenon, we in- of all pregnancies are complicated by a fetal arrhyth- cluded in the treatment additionally oral amiodarone, mia. Although, in most of the cases they are benign and preserving myocardial contractility, because the treat- of short duration, 1–3 % is complicated and can lead to ment and prognosis of SVT depends not only of sup- pression rate of SVT but recovery from fetal congestive Sokol V. et al. Digoxin and amiodaron in fetal sustained supraventricular tachycardia and nonimmune hydrops heart failure and hydrops as well.12 Digoxin is cardiac vaginal delivery is recommended and newborns are glycoside and for a long time prominent drug in the treated for at least 6–12 months.9 In the case of cesarean therapy of congestive heart failure. It has positive ino- section, the maturity of fetal lungs must be verified to tropic and negative chronotropic properties that increase avoid neonatal adverse affects. One third or more ne- cardiac output and decrease heart rate. With these char- onates postnatally will be free of further SVT probably acteristics, digoxin prolongs the refractoriness of the due to involution of the abnormal pathway.
AV node and terminates the circular movements within re-entrant circuit so that aberrant wave of excitation Conclusion
reaches depolarized tissue.5 Digoxin is effective and nontoxic in relatively narrow serum range (0.8 – 2.0 ng/ Sustained fetal SVT with instability rates of ventricu- mL), so the optimum therapy for pregnant women or lar rhythm and prolonged duration can be serious condi- fetus requires an accurate measurement of serum dig- tion in which the fetus is at significant risk for develop- oxin levels.13 During pregnancy increased digoxin dos- ing congestive heart failure and hydrops, neurological age may be necessary because of enhanced renal clear- damage and intrauterine death. Vigilant fetal heart rate ance and expanded blood volume. Reported fetal : ma- control and ultrasound monitoring as well as adequate ternal (F:M) plasma concentration ratios vary from 0.4 selection of antiarrhythmic drugs are crucial in tachyar- to 0.9.14,15 However, in case of fetal hydrops, this ratio is rhythmia suppression and hydrops resolution. Digoxin reduced because the placental transfer of the digoxin is and oral amiodarone with its favorable effect on myo- limited. In addition, conversion to sinus rhythm with di- cardial contractility and well known amiodarone high goxin is achieved in 50% of nonhydropic fetuses and conversion rate in fetal SVT complicated by hydrops only in 15–25% in hydropic fetuses.5,16,17 Hence, medi- were proper option in terms of management outcome.
cation with good placental transfer, such as amiodarone, should be used from the beginning of fetal treatment for hydrops. Digoxin has a few maternal side effects which References
are related to overdosing like nausea, vomiting and headache.4 There also can be found maternal cardiac ad- 1. Strasburger JF, Wakai RT. Fetal cardiac arrhythmia detec- tion and in utero therapy. Nat Rev Cardiol 2010;7(5):277–90.
verse effects such as ventricular extrasystoles or heart block that was seen in our case.
2. Maeno Y, Hiroshe A, Kanabe T, Hori D. Fetal arrhythmia: prenatal diagnosis and perinatal management. J Obstet Gynaecol Because of low conversion rate with digoxin, second line drugs are frequently required to achieve sinus 3. Rubart M, Zipes DP. Genes and cardiac repolarization: the rhythm as it was in our case with inclusion of amiodar- challenge ahead. Circulation 2005;112(9):1242–4.
4. Oudijk MA, Ambachtsheer EB, Stoutenbeek P, Meijboom Amiodarone prolongs the repolarization of the myo- EJ. Protocols for the treatment of supraventricular tachycardias cardium. A large study by Strasburger et al.18 was pub- in the fetus. Ned Tijdschr Geneeskd 2001;145(25):1218–9.
lished in which amiodarone had a 93% successful rate 5. Naheed ZJ, Strasburger JF, Deal BJ, Benson DW Jr, Gid- of conversion as second line therapy in fetal SVT tachy- ding SS. Fetal tachycardia: mechanisms and predictors of hy- cardia complicated with hydrops. Treatment with amio- drops fetalis. J Am Coll Cardiol 1996;27(7):1736–40.
darone has been associated with transient biochemical 6. Strasburger JF, Cheulkar B, Wichman HJ. Perinatal ar- neonate hypothyroidism, maternal photosensitive skin rhythmias: diagnosis and management. Clin Perinatol 2007;34 rash and thrombocytopenia. In addition, amiodarone is a suitable second line treatment in hydropic SVT and 7. Jaeggi ET, Nii M. Fetal brady- and tachyarrhythmias: new because of unsignificant possibility of proarrhythmic and accepted diagnostic and treatment methods. Semin Fetal events in distinction of flecainide and sotalol. Amiodar- one administration has been found to increase the steady-state digoxin concentration, and maintenance 8. Guntheroth WG, Cyr DR, Shields LE, Nghiem HV. Rate- based management of fetal supraventricular tachycardia. J Ultra- doses of digoxin should be decreased by ≥50%.19 There is also a question whether to treat prenatally or 9. Suri V, Keepanaseril A, Aggarwal N, Vijayvergiya R. Pre- postnatally. The decision mainly depends on gestational natal management with digoxin and sotalol combination for fetal age and in early gestational weeks prenatal treatment is supraventricular tachycardia: case report and review of litera- the reasonable management. However, if hydrops does ture. Indian J Med Sci 2009;63(9):411–4.
not resolve in 2 weeks, postnatally treatment is recom- 10. Cuneo BF, Strasburger JF. Management strategy for fetal mended.2 Transplacental therapy is proper mode of tachycardia. Obstet Gynecol 2000;96(4):575–81.
therapy in nonhydropic fetuses and first choice in hy- 11. Zales VR, Dunnigan A, Benson DW Jr. Clinical and elec- dropic fetuses. But, when conversion to sinus rhythm is trophysiologic features of fetal and neonatal paroxysmal atrial not achieved, direct fetal therapy should be recom- tachycardia resulting in congestive heart failure. Am J Cardiol After successful fetal rhythm conversion, dosage is 12. Amiodarone Trials Meta-Analysis Investigators. Effect of maintained till delivery. If the heart rate is controlled, prophylactic amiodarone on mortality after acute myocardial in- Sokol V. et al. Digoxin and amiodaron in fetal sustained supraventricular tachycardia and nonimmune hydrops farction and in congestive heart failure: meta-analysis of indi- 16. Van Engelen AD, Weijtens O, Brenner JI, Kleinman CS, vidual data from 6500 patients in randomised trials. Lancet Copel JA, Stoutenbeek P, Meijboom EJ. Management outcome and follow-up of fetal tachycardia. J Am Coll Cardiol 1994; 13. Graves SW, Valdes R Jr, Brown BA, Knight AB, Craig HR. Endogenous digoxin-immunoreactive substance in human 17. Oudijk MA, Ruskamp JM, Ambachtsheer BE, Ververs pregnancies. J Clin Endocrinol Metab 1984;58(4):748–51.
TF, Stoutenbeek P, Visser GH, Meijboom EJ. Drug treatment of 14. Maxwell DJ, Crawford DC, Curry PV, Tynan MJ, Allan fetal tachycardias. Paediatr Drugs 2002;4(1):49–63.
LD. Obstetric importance, diagnosis, and management of fetal 18. Strasburger JF, Cuneo BF, Michon MM, et al. Amioda- tachycardias. Br Med J 1988;297(6641):107–10.
rone therapy for drug-refractory fetal tachycardia. Circulation 15. Rogers MC, Willerson JT, Goldblatt A, Smith WT. Serum digoxin concentrations in the human fetus, neonate and infant. N 19. Hauptman PJ, Kelly RA. Digitalis. Circulation 1999;99 Paper received: 16. 02. 2011; accepted: 02. 03. 2011.
Address for correspondence: Dr. Vesna Sokol, Department Obstet. & Gynecol. Univ. Medical School of Zagreb, Petrova 13, 10000 Zagreb, Croatia U ^ASOPISU »GYNAECOLOGIA ET PERINATOLOGIA«
OBJAVLJENE PREPORUKE (SMJERNICE)
HRVATSKOG DRU[TVA ZA PERINATALNU MEDICINU HLZ-a
1) Novoro|en~e s mekonijskom plodovom vodom (str. 181/2008).
2) Primjena prostaglandina u novoro|en~adi sa sr~anom gre{kom (str. 182/2008).
3) Smjernice za prerano prijevremeno prsnu}e vodenjaka (str. 132/2009).
4) Europske smjernice za lije~enje neonatalnog sindroma respiratornog distresa (str. 140/2009).
5) Novoro|ena~ki RDS (str. 160/2009).
6) Antibiotska profi laksa rane neonatalne sepse uzrokovane beta hemoliti~kim streptokom grupe B (str. 119/2010).
7) Prijete}i prijevremeni porod (str. 121/2010).
8) Trudno}a/porod nakon ranijega carskog reza (str. 123/2010).
9) Prenatalni probir i dijagnostika kromosomopatija (str. 125/2010).
10) Antenatalni »in utero« transport djeteta (str. 54/2011).

Source: http://www.gynaecolperinatol.com/files/pdf/v20n1_44-47.pdf

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