Tuesday, July 31, 2012

Subarachnoid Hemorrhage And Pregnancy (PART 3)

Other consideration:(4)
Fluids and electrolyte changes occur as a result of the increase in interstitial fluid by as much as 6 litres.To maintain this isotonic hyperhydration sodium is retained. 
Although total body sodium is increased the serum sodium is 2-3 meq/L below non pregnant level.
The infusion of sodium free fluids such as 5% dextrose in water can lead to hyponatremia in mother and neonate (Lind,1983), potassium levels are also somewhat lower in pregnancy.

Plasma osmolality is reduced by as much as 10 mosm /kg H20(Hytten 78) within the first few weeks of pregnancy due to the fall in electrolyte and urea. Urea falls in early pregnancy to about a quarter of normal values and continues to fall slightly throughout pregnancy possibly due to the increased renal clearance.Similarly creatinine and uric acid levels falls.

Fasting glucose levels are decreased by the 10th week of pregnancy. Glycosuria however is common making the diagnosis of gestational diabetes dependent on fasting blood sugar levels.
Periods of starvation should be restricted to the minimum necessary for anesthetic safety as rapid increase in ketone production can occur.

Serum alkaline phosphatase rises to about 4 times normal in pregnancy as it produced by the placenta in normal women.

Marked leucocytosis occurs due to an increase in the neutrophil polymorphnuclear cells.The erythrocyte sedimentation rate is not value in pregnancy as a nonspesific sign of disease.It is usually very high possibly due to the high levels of plasma globulins and fibrinogen.

How the mother's immunological system deals with the fetal allograft is not known. Certainly she can still respond with anaphylactic reactions to drugs (Lund,1980,Bareka 1980).The hypotension and bronchospasm of such response can be lethal to the fetus eventhough the mothers survives.


The developing fetus and anesthethics:(4,5)
The risk of anesthesia for the mother is proportionate to gestation. The risk to the fetus of anesthesia are however in inverse proportion to its gestational age.(Broadsky et all 1980).

It is estimated that 30% of pregnancies abort 
spontaneously.It is not known wether anesthesia in early and as yet undiagnosed pregnancy does increase the rate of fetal loss. It seems certain that some drugs and enviromental factors can cause fetal loss during the first week of pregnancy before implantation has occured and its possible that anesthesia may also cause fetal death at this early stage.


Organogenesis takeplace in the fetus from second to the tenth week of gestation and during this period, when pregnancy is often not yet diagnosed teratogenic affects may occur.However even during this very vulnerable fetal stage,it seems possible that the most likely effect of drugs would be fetal death.

By the end of the first trimester the differentiation of embryonic cells into organ is completed and congenital malformations can no longer becaused by the drugs. But it is possible that fetal death may result from the action of drugs ,or the indirect effect of anesthesia or surgery. Fetal loss of 23% indiagnosed pregnancy has been reported following laparatomy (Saunders and Milton, 1973) and 30% following cervical sutures(Shinder and Loebster 1965).
Many different factors may play a part in these very high rates of fetal loss and there is no evidence that any particular anesthetic technique is involved.Teratogenic damage to the fetus is the most feared side effect of drugs during pregnancy.It is seems essential thay any drugs that does have teratogenics effects must cross the placenta (Beeley 1981).

But this is not an inevitable consequence of drugs that cross the placenta even at this stage of organogenesis.
All drugs that affect the mother's CNS must also cross the placenta and are thus treated with suspicion early in pregnancy.
Thalidomide cause congenital abnormalities in only a quarter of the cases at the same stage of development. 

Several factors may be involved in damage to the fetus including enviromental factors.
Other drugs are suspected of teratogenic potentially,such as alcohol,phenytoin,warfarin,lithium and quinine.
Many more have a lesser index of suspicion such as barbiturate,phenothiazine,diazepam and chronic low dose inhalational agents especially N20.

Even so the evidence seems to point to a possible rise in spontaneous abortion rate rather than congenital malformation (Vesseg and Nunn,1980) in those working in the theatre and also in women undergoing.
Anesthesia in the first trimester of pregnancy (Heinomen et al 1977). No anesthetic drugs other than N20 has been directly implicated in causing congenital abnormalities.
Many factors other than teratogenicity may be involved in the apparent rise of fetal loss associated with anesthesia.
Indirect effect such as a fall in placental perfusion,anoxia
relative hypercarbia,hyperpyrexia,acidosis and fluid and electrolyte imbalance may all cause the death of the fetus without apparent ill effects on the mother.Direct effects of anesthetic drugs on the fetus may cause exagerated effects on fetal physiology such as a reduction in fetal cardiac output resulting in death.

Monitoring maternal temperature between 37-37,5 C is important as fetal wastage is high following pyrexia from any cause.


Anesthetic consideration :(4)
All elective surgery should be postponed until after pregnancy. Anesthesia in the first trimester should be avoided whenever possible if fetal survival is desired.But if it does take place it seems more possible that fetal death rather than malformation will result.
Therapeutic abortion is therefore not advised.
Pregnancy should be excluded in all women in whom it is possibly before elective surgery is undertaken.

New drugs which of necessary have not been tested for teratogenicity should not be used in the first trimester if fetal survival is desired eventhough there is some benefit from the drug.
New sedatives,metoclopromide,and H2 antagonist have not been shown to be safe from teratogenic effects and should be avoided when possible.


Effects of Anesthetic and Analgesic drugs:(4,5,6)
Non anesthetic factors :
Anxiety: Morishima et al 1978 have experimentally established and reproduced fetal asphyxia induced by psychological maternal stress.


Pain:(5)
The pain of labor produces an increase in maternal blood cathecolamine and decrease in UBF and therefore in fetal oxygenation (Shnider 1971).
Maternal cathecolamines decrease intrauterine pressure and frequency of contractions.However it is still uncertain wether the small amount of epinephrine added to local anesthetic for epidural analgesia during labor affects the duration of labor (Albright et all 1981).
Epidural analgesia decreases the maternal cathecolamine level and restores UBF as well as a decreasing sympathetic activity and vasoconstriction caused by painful uterine contractions(Shnider et all 1980).


Drugs :(2,3,5,6)
Drugs administered during pregnancy can have fetal or maternal side effects and interact with anesthetic drugs.
Betamimetics are prescribed in obstetrics as tocolytic (Jouhet 1981). The drugs most often used in France
(salbutamol,ritodrine) have predominant beta-2 action but also have beta-1 actions,which can cause maternal side effects both cardiovascular (tachycardia,hyper or hypo
tension),fetal tachycardia and metabolic (hypoglycaemia,
maternal and fetal hyperinsulin,lipolysis).
Pulmonary edema and cardiac failure have been reported when betamimetics are used,especially when used with corticosteroids to accelarate fetal lung maturation (Millier,1980).

The interactions of these drugs with some anesthetics are known :
1.Cardiovascular effects of betamimetics can be poten
   tiated by halogenated anesthetics and produce cardiac 
   arrythmia.


2.Muscle relaxant such as succinylcholine can have cardio
   vascular side effects potentiated by betamimetics.


3.Regional anesthesia can produce hypotension,with 
   betamimetics these effect may be increased and induce 
   acute fetal distress.


Antihypertensive therapy :
Betablocker and especially propranolol increase fetal and neonatal vulnerability to hypoxia by preventing increases in cardiac output. After blockade of betareceptors,the neonate may have bradycardia and hypoglycaemia and delayed pulmonary fluid resorption after birth.
These effects can be correlated with the neonatal phar
macokinetics of the betablocker (Boutroy et all 1981).
The pharmacokinetics of propranolol are modified by cimetidine which is sometimes administered as a preme-
dication for emergency can to avoid the acid aspiration syndrome (Mc Coughey et all 1981).
If the propranolol and cimetidine are administered together the blood level is higher than otherwise(Howe et all 1980).
As cimetidine is transfered across the placenta neonatal side effects of propranolol could be increased although this is not yet been reported.

But a bolus of esmolol (0,5 to 1mg/kg) may be critical in preventing aneurysm rupture. Methyldopa is very useful for antihypertensive therapy during pregnancy. 
A recent study has demonstrated that neonate from mothers who receive methyldopa have a significant decrease in systolic blood pressure(SBP) for two days after birth(Whitelaw, 1981).

Hazard of anesthetic drugs to both the mother and the neonate are increased by the use of antihypertensive drugs.
Drugs that are potentially toxic include nitropruside ,betablockers and mannitol. Although nitropruside may decrease UBF and cause fetal cyanide toxicity one or two boluses of 25 to 100 mcg may be extremely useful during laryngoscopy and intubation.
Both nitropruside and betablocker given briefly in bolus form before delivery are unlikely to produce fetal problem.


Mannitol has been shown to cross the placenta and it may accumulate in the fetus and lead to change in fetal osmolality,volume and the concentration of various electrolytes. In human study the administration of 200 g of mannitol to the mother before delivery altered 
the volume, osmolality and concentration of solutes in 
the fetus. 
However in dosage used clinically in aneurysm clipping (0,5 to 1 g/kg) mannitol is unlikely to cause severe fluid or electrolyte abnormalities on the fetus.
Mannitol is also not always essential for brain relaxation
however if it is required moderate doses should be used.


All drugs used for relief of apprehension and pain during labour and delivery cross the placenta and affect the baby who is markedly susceptible to the depressant effect of drugs used in labour.
Conway and Brackbill 1970 evaluated the neonatal effects of a number of anesthetic and analgesic drugs and described muscular hypotonia, decreased level response to auditory stimuli,and decreased visual attention and all these signs lasted for one month.
The most widely used narcotics is pethidine(mepheridine)
by im at a dose of 50 to 100 mg or intravenous 12,5  to 
30 mg, neonatal respiratory depression is slight unless there is fetal distress or other central depressant drugs have been administered before pethidine.
The use of narcotics whatever the way of administration carries a risk of respiratory depression to the neonate so an antagonist is essential in the delivery room. Naloxon is the agent of choice. Neonatal respiratory depression may occur after moderate maternal administration of narcotic
especially if there has been fetal asphyxia. 
Neonatal injection of naloxone (0,04 mg iv or 0,2 mg im) should be given after ventilation resuscitation (Lassner et all 1978).


Inhalation analgesia :(3,5,6)
N20 can be offered throughout labour for intermittent analgesia, selfadministered by the mother or administered by the midwife or doctor,70% of mothers have reasonable pain relief with a mixture of 50%N20 and 50% oxygen. The concentration is safe for the mother and fetus and does not cardiorespiratory depression or affect the progress of labour. A premix concentration of 50% N20 and 50% 02 (Entonox) is available in the VK and most of Europe 
 allowing self administration without the risk of oxygen failure.
Increasing the dose and duration of N20 anesthesia before delivery carries with the risk of producing diffusion hypoxia in the neonate.
If the induction delivery period exceeds 20 minutes,N20 should be stop.


Halothane used in 0,5% concentration is a good supple-
mental anesthetic to N20 for ceasarean section, in higher concentrations it depresses uterine tone.During vaginal delivery this effect may be used to treat uterine hyper
contractility or to facilitate intrauterine manipulation.
The halogenated agents do not cause important depres
sion of neonate. If absolutely necessary isoflurane seems  
a good choice because it maintains uterine blood flow in experimental animals at levels of 1,5 MAC.


Thiopental in less than a 250 mg dose does not produce an important degree of depression of the nonate.
Tranquilizers are administered iv and/or im for treat apprehension early in labour;promazine 25-50 mg,prome-   
thazine 25-50mg,propromazine 10-20 mg and hydroxyzine 25-50 mg. These drugs should be given carefully when combined with sedative or narcotics because ventilatory and cardiovascular depression in the mother and the baby.


Ergot alkaloids and vasopressors administered together or following one another may lead to severe hypertension and cerebrovascular accidents.The only agents that do not cross the placenta (except gallamine) are muscle relaxant.


Drugs in Breast milk :(4)
Analgesia and anesthesia in the puerperium cause concern when the mother is breast feeding as the effect of the drugs on the neonate may be undesirable. Analgesic and anesthetics are all lipid soluble drugs that are distributed throughout the body and in the milk.
For similar pharmacokinetics reason drugs in the milk would be absorbed by the neonate.Therapeutic doses of analgesic and anesthetic drugs used for short periods of time do not result in neonatal sedation of prolonged duration.These drugs are highly protein bound in the mother and only very small quantities of free drug are able to cross to the milk.

Here futher protein binding occurs but less in plasma. 
Milk has a lower pH than plasma so weakbases such a narcotics, benzodiazepines and phenothiazines can reach higher concentrations in the milk than weak acids such as barbiturate. However,although these lipid soluble drugs diffuse into the milk already present in the breast between feeds, incomplete equilibration occurs because of the changing plasma levels and rate of milk production.The volume of milk the baby ingest is small and the low level of drug in the milk prevents therapeutic level being obtained in the baby's plasma.
However it is possible that the baby may have an allergy to a drug in less than therapeutic dose.
Breast feeding is no justification for following the mother poor analgesic in the puerperium when pain can be considerable from abdominal of perineal wounds.

to be continued





















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