General Anesthetic Drugs Used during Labor –Effects on the baby

General Anesthetic Drugs  –Effects on the baby

Neonatal drug depression is minimized by keeping drug dosage levels low in the mother and by keeping the induction delivery interval as short as possible. Avoiding aortocaval compression, hypotension or hypoxia in the mother ensures that the infant is not hypoxic.

                Maternal safety during general anesthesia remains unpredictable. The danger of inhalation of stomach contents, especially in patients undergoing emergency cesarean section, continues to be a significant cause of maternal death. For this reason conduction anesthesia for surgical delivery of patients in labor is gaining popularity. However, general anesthesia remains essential for a small number of obstetric patients.

                The intravenous induction agents that are in widespread use in obstetric anesthesia, thiopentone, methohexitone and althesin, cross placenta so rapidly that it is not possible to deliver the baby before some quantity of the drug has been transferred; detectable levels occur within 30 seconds of an intravenous dose. However, the newborn appears not to be affected with these levels since the drugs, after crossing the placenta from the umbilical vein, pass through the fetal liver where some is metabolized. /the drug level in the infant’s brain is further lowered by dilution with less contaminated blood from the fetal legs and abdomen. The drug concentration very rapidly declines in the mother after a single dose as the drug I redistributed throughout her circulation. This ensures that the level continues to fall in the fetus.

                Volatile anesthetic agents are generally added to the inspired mixture to ensure maternal unawareness. The halogenated agents, halothanes, methoxyflurane and enflurane allow the mother a 50% oxygen proportion in the inspired air and may improve uterine blood flow. These agents do not increase postpartum uterine bleeding unless used in very high doses. They do not depress the newborn.

                Muscle relaxants cross the placenta in clinically insignificant amounts; succinyl choline I very rapidly metabolized by the pseudocholinesterase in the mother’s plasma. The non-depolarizing. Longer acting relaxants are very large molecules that are highly ionized and so are unable to cross the placenta.

                Nitrous oxide used intermittently or continuously for pain relief in normal labor does not cause maternal cardiovascular depression or alters uterine contractility, and it is safe for the fetus in concentrations of up to 50% in inspired air. However, nitrous oxide ad oxygen, when used alone for cesarean section without supplementary inhalational agents, has resulted in neonatal depression. This is possibly caused by decrease uterine perfusion following high endogenous catecholamine levels that are associated with this very light anesthesia.

                The premixed cylinders of 50% nitrous oxide and oxygen have been shown to give considerable analgesia. But timing of administrations is not easy when they are used intermittently, and thus analgesia is less efficacious than continuously inhaled self- administered nitrous oxide.

Local Anesthetic Drugs -Effects on the Baby

Local Anesthetic Drugs Used During Labor –Effects on the Baby

Conduction anesthesia has become the most commonly used in modern obstetric practice, both to provide analgesia for labor pain and anesthesia for surgical delivery. Epidural blocks give a versatile range of anesthesia from a mild sensory block for normal labor to a dense blockade of most of the nerve fibers required for cesarean section.

                The local anesthetics commonly used for obstetrics are bupivicaine and lignocaine. When injected, these drugs are absorbed from the epidural space into the maternal blood stream. This results in a significant level of circulating drug which will cross the placenta rapidly by passive diffusion. Many factors affect the placental transfer such as the total dose of drug injection, route of administration, presence of adrenalin, maternal metabolism and exertion, maternal protein binding and intervillous blood flow. These factors determine the fetal-to-maternal concentration ratio. Pathological conditions of the placenta such as eclampsia, diabetes, hyper-tension, and Rhesus disease may also affect this transfer but the extent to which they do so is unknown. The local anesthetic is taken up by the fetus and metabolized and excreted by the baby. Similar, though delayed, decay curves of drug activity are a seen in neonatal and maternal circulations.

                Local anesthetics act on all conduction tissue and toxicity in the fetus and neonate is seen in the central nervous system, peripheral blood vessels and the heart. No fetal heart rate changes occur at modest plasma levels of local anesthetic.

                Conduction anesthesia also has indirect effects on the fetus, which requires an adequate delivery of oxygenated maternal blood to the intervillous space. This can be affected by changes in the uterine blood flow, which varies directly with perfusion pressure across the uterine vascular bed, and in aversely with uterine vascular resistance. So, if hypotension results from an epidural block, a reduction in mean uterine pressure will reduce uterine blood flow and thereby impair fetal oxygenation and well-being. Hypotension is a common complication of epidural block, especially at term when pooling of blood in the lower limbs in encouraged not only by sympathetic blockade but by aortocaval compression.

                Uterine vascular resistance is maintained by the intrinsic vasomotor state of uterine vessels. These are fully dilated at term but ill constrict with high catecholamine levels, general anesthesia and toxic levels of local anesthetic drugs.

Antibiotics in Pregnancy

Antibiotics in Pregnancy

Antibiotics which are safe for pregnancy penicillin, erythromycin clindamycin cephalosporins.

Prophylactic Antibiotics

Ampocillin, amoxicillin, cefazolin, and erythromycin/sulbactam are the safest drug to treat the preterm premature rupture of membrane, prevention of bacterial endocarditis and during cesarean section, urinary tract infection, chorio-amnionitis and group B streptococci.

Antibiotics to be avoided

Following drugs to be avoided:

Ø  Amino glycosides = eight cranial nerve damage

Ø  Erythromycin estolate = hepatotoxic to mother

Ø  Fluoroquinolones = potentially mutagenic, cartilage damage, arthopathy, teratogenicity

Ø  Ribavarin = possibly fetotoxic

Ø  Tetracyclines = staining of deciduous teeth.

Drug Induced Acute Renal Failure in Pregnancy- Management

Drug Induced Acute Renal Failure in Pregnancy

Acute renal failure is a most challenging clinical problem when it occurs in pregnancy. It requires an understanding of the normal physiology of the kidney in pregnancy and the natural history of different underlying renal diseases when pregnancy occurs.

                Acute renal failure defined as the condition in which the urine volume falls below 400 ml in 24 hours. Anuria is the absence of excretion of urine in 12 hours whereas oliguria is the term given to clinical condition.

                Because patients with chronic renal disease may present with worsening proteinuria, hypertension, and renal function, these disorders must be excluded from those conditions that cause acute deterioration of renal failure in otherwise normal women during pregnancy. As in all patients who develop acute renal failure, perennial, renal and post renal obstructive causes must be excluded.

Causes of Renal Failure

Drugs

·         Hemodynamic affects

·         Acute allergic interstitial nephritis

·         Direct toxicity to tubule

Pathogenesis

Reversible prerenal acute Renal Failure

Homodynamic disturbances can initially produce acute renal dysfunction that has the potential to be rapidly reversed, prompt recognition and treatment is important.

                Prolonged under perfusion of kidney may lead to failure of the compensatory mechanisms and hence a acute decline in GRR. The renal tubules are intact and become hyper functional: that is, tubular reabsortion of sodium and water is increased, partly through physical factors associated with changes in blood and urine flow and partly through influence of angiotensins, aldosterone and vasopressin. This leads to formation of low volume urine which is concentrated but low in sodium. These urinary changes may be absent in patients with impaired tubular function, e.g. pre-existing renal impairment, or those who have received loop diuretics.

Established Acute Renal Failure

Established ARF may develop following severe or prolonged under perfusion of kidney. In such cases, the histological pattern of acute tubular necrosis is usually seen. In patients without an obvious cause of prerenal ARF, alternative ‘renal’ and ‘post renal’ causes must be considered.

Ischemic tubular necrosis usually follows a period of shock, during which renal blood flow is greatly reduced. Even when systemic hemodynamic are restored, renal blood flow can remain as low as 20% of normal, due to swelling of endothelial cells of glomeruli and per tubular capillaries, and edema of the interstitium. Blood flow is further reduced by vasoconstrictors such as thromboxane, vasopressin, noradrenaline and angiotensin II, partly counterbalanced by release of intrarenal vasodilators prostaglandins. Thus in ischemic ATN there is reduced oxygen delivery to tubular cells. These cells are vulnerable to ischemia because they have high oxygen consumption in order to generate energy for solute reabsorption, particularly in thick ascending loop of henle.

The ischemic insult ultimately causes death of tubular cells, which may shed into the tubular lumen causing tubular obstruction. Focal breaks in the tubular basement membrane develop, allowing tubular contents to leak into the interstitial tissue and cause interstitial edema. In nephrotoxic ATN a similar sequence occours, but it is intitiated by direct toxicity of causative agent to tubular cells. Examples include aminoglycoside antibiotics such as gentamicin, cytotoxic agent cisplatin and the antifungal drug amphotericin B.

Clinical Presentation

The clinical presentation of both these conditions should be apparent, and appropriate diagnosis and treatment can then be promptly instituted. Renal cortical necrosis is another cause of renal failure that occurs more frequently in pregnancy and it must be differentiated from the many causes of acute tubular necrosis that may be associated with pregnancy. Those conditions that cause renal failure unique to pregnancy must always be considered when renal function deteriorates in the last trimester or the postpartum period. Severe pre-eclampsia, acute fatty liver of pregnancy and idiopathic postpartum acute renal failure may all present similar complications but the approach to each or these clinical disorders must be individualized. By understanding the causes of renal functional deterioration in pregnancy, a logical differential diagnosis can be established, allowing appropriate therapeutic decisions to preserve both maternal and fetal well-being.