Tocolisis

Jorge Luis Nuez Pizarro

Introduccion
La labor pretrmino (LPT) precede el 50% de partos
pretrmino, pero aproximadamente el 30% se resuelve
espontanemente y slo el 10% da a luz en los primeros 7 das
(el 50% de las pacientes hospitalizadas por LPT tiene un parto
a termino). La terapia tocoltica cesa las contracciones
tempralmente, pero no remueve el estimulo causal; por lo que
es util para horas a dias, pero no para semanas o meses.
No partner Systemic infection
Low socioeconomic status Bacteriuria
Anxiety Periodontal disease
Depression Placenta previa
Life events (divorce, separation, death) Placental abruption
Occupational issues
Vaginal bleeding, especially in more than one
trimester
Abdominal surgery during pregnancy Previous preterm delivery
Multiple gestation Substance abuse
Polyhydramnios Smoking
Uterine anomaly Maternal age (<18 or >40)
Uterine leiomyoma African-American race
Diethylstilbestrol-induced changes in uterus Poor nutrition and low body mass index
History of second trimester abortion Inadequate prenatal care
History of cervical surgery Anemia (hemoglobin <10 g/dL)
Premature cervical dilatation or effacement (short
cervical length)
Excessive uterine contractility
Sexually transmitted infections Low level of educational achievement
Pyelonephritis, appendicitis, pneumonia Genotype
Systemic infection Fetal anomaly
Environmental factors (eg, heat, air pollution) Fetal growth restriction
Labor pretrmino
Clnica no especfica (puede presentarse varias horas antes)
Clicos parecidos a menstrual
Contracciones leves e irregulares
Dolor lumbar
Sensacin de presin en la vagina
Secrecin vaginal de moco (claro, rosa o ligr sanguinolento)

Dx: Clnico. Eco tv es la mejor manera de medir cuello (<30cm
riesgo)
Contracciones: 4 every 20 minutes or 8 every 60 minutes.
Incorporacin 80%; dilatacin >2cm.
Triaje basado en longitud de cuelo (>30cm: bajo riesgo 20cm:
alto riesgo) Fibronectina fetal como predictor. (ayuda a
diferenciar de Braxton Higgs)
Indicaciones
Slo indicado en gestantes con una edad gestacional en la que el
feto se beneficia de un retraso de 48h del parto.
1. Evaluacin inicial
2. Objetivos: 1) Demorar parto al menos 48h para alcanzar efecto
mximo profilctico de corticoides. 2) Dar tiempo para el traslado
de la madre. 3) Si se sospecha de causa transitoria (infecciosa o
ciruga)
3. Contraindicaciones:
Muerte fetal
Anomala fetal letal
Status fetal no reactivo
Preeclampsia o eclampsia severa
Hemorragia materna con inestabilidad hemodinmica
Infeccin intraamnitica
Contraindicacin materna a la droga tocoltica



Tratamiento
Systematic review and network meta-analysis of 95 randomized
trials of tocolytic therapy for preterm labor, all of the commonly
used tocolytic agents (cyclooxygenase inhibitors, beta-adrenergic
receptor agonist, calcium channel blockers, magnesium sulfate,
oxytocin receptor antagonists) were statistically more effective
than placebo/no therapy for delaying delivery for 48 hours (odds
ratios compared toplacebo/no treatment ranged from 1.91 to 5.39)
[18]. Cyclooxygenase inhibitors and calcium channel blockers had
the highest probability of delaying delivery and improving neonatal
and maternal outcomes. However, prolongation of pregnancy was
not associated with a statistically significant reduction in overall
rates of respiratory distress syndrome or neonatal death. This may
be related to the rarity of neonatal death and inconsistency in
definitions and reported outcomes among trials.
Haas DM, Caldwell DM, Kirkpatrick P, et al. Tocolytic therapy for
preterm delivery: systematic review and network meta-analysis. BMJ
2012; 345:e6226.

Atosiban
Inhibidor competitivo de receptores de oxitocina.
FDA no lo aprob. Us en Europa.
A recent Cochrane review (Papatsonis et al, 2005) did not
demonstrate any superiority of atosiban over beta-agonists
or placebo in terms of tocolytic efficacy or infant outcomes.
Compared with beta-agonists, there were more atosiban-
exposed infants with birth weights under 1500 gms (RR 1.96;
95% CI 1.15 to 3.35, 2 trials, 575 infants), and no overall clear
benefit on in perinatal or neonatal outcomes
Initial intravenous injection of 6.75mg in 0.9ml slowly
injected over one minute
A continuous infusion at a rate of 24 ml/hr up to 3 hours
A continuous infusion at a rate of 8ml/hr up to 45 hours

Inhibidores Ciclooxigenasa
(indometacina)
Por su eficacia, seguridad y costo-efectividad, se considera de
primera linea hasta las 32ss. (2-A)
Prostaglandinas son esenciales para el labor de parto. Tanto la COX1
como la COX2 son producidas por la placenta, teniendo ms
importantcia la COX2 durante el parto.
Compared to the other drugs, COX inhibitors were associated with a
trend toward reduction of birth within 48 hours of initiation of
treatment (RR 0.59, 95% CI 0.34-1.02) The effect was more robust
when COX inhibition was only compared with beta-adrenergic
receptor agonists (RR 0.27, 95% CI 0.08-0.96).
50 to 100 mg loading dose (may be given per rectum), followed by
25 mg orally every four to six hours
If indomethacin is continued for longer than 48 hours, sonographic
evaluation for oligohydramnios and narrowing of the fetal ductus
arteriosus is warranted at least weekly
Informacin limitada sobre COX2 selectivos.
Bloqueadores de canales de
calcio
Disminuye el ingreso y liberacin por el retculo
sarcoplasmtico de Ca, lo que disminuye la interaccin entre
cadenas de actina y miosina, disminuyendo contractibilidad.
Compare with Beta-agonist, use of nifedipine was also
associated with significant reductions in risk of respiratory
distress syndrome, necrotizing enterocolitis, intraventricular
hemorrhage, neonatal jaundice, and admission to the
neonatal intensive care unit, and had a better side effect
profile.
De primera linea entre las 32 y 34ss. (2-B)
30 mg loading dose and then 10 to 20 mg every four to six
hours
Agonistas beta adrenrgicos
( terbutaline)
Se une al receptor beta-2 e incrementa adenil ciclasa
intracelular, activando a la proteinkinasa y fosforilando
proteinas intracelulares, lo que disminuye el Ca libre y
finalmente, la interaccion entre actina y miosina,
disminuyendo la contractibilidad.
0.25 mg can be administered every 20 to 30 minutes for up to
four doses or until tocolysis is achieved
Monitorizar FC materna (parar si >120xmin), K y glucosa.
Sulfato de Magnesio
Mecanismo de accin no claro. Compite con calcio en
membrana celular.
In 15 comparative trials, magnesium sulfate was neither more
nor less effective than other tocolytics.
Review from 4 meta-analisis evidence there was no evidence
of a clinically important tocolytic effect of magnesium sulfate
Efecto neuroprotector sobre neonato. (We limit magnesium
sulfate for neuroprotection to pregnancies less than 32 weeks
of gestation). Descontinuar tras 24h. Este efecto no debe
condicionar eleccin de tocoltico.
6 g intravenous load over 20 minutes, followed by a
continuous infusion of 2 g/hour. Puede ajustarse de acuerdo a
toxicidad materna y efectividad en contracciones.

Donadores de oxido ntrico
Incrementa el cGMP mediante la interaccin la guanilato
ciclasa. Esto interacciona con la cadena de miosina
produciendo relajacin del musculo liso.
There is insufficient evidence to recommend NO donors for
inhibition of preterm labor
10 mg glyceryl trinitrate patch applied to the skin of the
abdomen. Aumentar otro parche si fuera necesario.
10ug/min en infusin intravenosa.
Referencias
UPTODATE
American College of Obstetricians and Gynecologists, Committee on
Practice BulletinsObstetrics. ACOG practice bulletin no. 127:
Management of preterm labor. Obstet Gynecol 2012; 119:1308.
King JF, Grant A, Keirse MJ, Chalmers I. Beta-mimetics in preterm labour:
an overview of the randomized controlled trials. Br J Obstet Gynaecol
1988; 95:211.
Gazmararian JA, Petersen R, Jamieson DJ, et al. Hospitalizations during
pregnancy among managed care enrollees. Obstet Gynecol 2002;
100:94.
Scott CL, Chavez GF, Atrash HK, et al. Hospitalizations for severe
complications of pregnancy, 1987-1992. Obstet Gynecol 1997; 90:225.
McPheeters ML, Miller WC, Hartmann KE, et al. The epidemiology of
threatened preterm labor: a prospective cohort study. Am J Obstet
Gynecol 2005; 192:1325.
Fuchs IB, Henrich W, Osthues K, Dudenhausen JW. Sonographic cervical
length in singleton pregnancies with intact membranes presenting with
threatened preterm labor. Ultrasound Obstet Gynecol 2004; 24:554.