Would Dipyrone work in treating malignant hyperthermia


Effects on the circulatory and other organ systems in the fetus.

In the last trimester of pregnancy, nonsteroidal anti-inflammatory drugs (NSAIDs) can lead to premature closure of the ductus arteriosus in the fetus (Mas 1999). A meconium analysis in newborns to clarify a possible connection between NSAIDs and persistent pulmonary hypertension (PPHN) found NSAIDs in the meconium (ibu-profen, naproxen, indomethacin and acetylsalicylic acid) in newborns with PPHN more than twice as often as in healthy children (Alano 2001).

The more mature the fetus, the greater the likelihood that its ductus arteriosus will close during anti-inflammatory therapy (Rasanen 1995). This effect was already observed from the 27th week of pregnancy (Bivins 1993). Before week 32, the fetal circulation should only respond in 5–10% of cases, with 32 weeks in 50% and from week 34 in 100% of cases (Moise, 1993, Moise et al., 1988). An apparently paradoxical effect was also observed after prenatal exposure to NSAIDs in newborns: a persistent ductus arteriosus. This had to be closed surgically (Norton 1993). The authors postulated that in this case indomethacin damaged the intima of the ductus and thus prevented spontaneous closure.

Premature duct closure can lead to pulmonary hypertension in the newborn, e.g. in a mature child whose mother has 75 mg a day in addition to heparin 2 weeks before delivery due to thrombophlebitis Diclofenac had received for 5 days. The pulmonary hypertension persisted and had to be treated with high doses of NO inhalation for 22 days. An apparently ischemic tricuspid valve reflux persisted even afterwards (Zenker 1998). Another case of pulmonary hypertension was described in a newborn with a closed ductus arteriosus who was delivered by caesarean section at week 39 due to fetal bradycardia. The mother had been treated with Diclofe-nac three days earlier (Siu 2004). In another case with 220 mg twice a day Naproxen Within the last 4 days before delivery, a mature child developed pulmonary hypertension 2 hours after birth with right heart hypertrophy and a closed ductus arteriosus. The symptoms normalized under oxygen therapy by the second day of life. After 5 months the child was clinically healthy, with slight echocardiography still detectable right heart hypertrophy (Talati 2000).

Fetal and neonatal kidney function can also be inhibited to the point of anuria if an NSAID was used in the last trimester of pregnancy. This effect is attributed to reduced kidney perfusion and an increase in circulating vasopressin (van der Heijden 1994, Walker 1994). The cases of necrotizing duck colitis (NEC) observed in newborns after prenatal exposure to NSAIDs are also explained by underperfusion in the fetus (Ojala 2000, Parilla 2000, Major 1994, Norton 1993). Renal dysfunction and NEC also occurred in newborns with persistent ductus arteriosus after birth Indomethacin wanted to close.

Finally, intracranial bleeding has also been described, particularly in premature infants, possibly as a result of an indomethacin-induced inhibition of platelet aggregation (Norton 1993).

It can be assumed that the organ disorders described as an example can occur in the fetus after administration of all NSAIDs (e.g. duct closure in Ketoprofen other Nifluminic acid; Radi 1999, Llanas 1996).

When acting primarily as a COX-2 inhibitor Nimesulide was reported in two case reports of kidney failure (requiring dialysis) in children after the mother had been treated in late pregnancy. In the second case it was 200 mg / day for tocolysis from weeks 26 to 32 (Balasubramaniam 2000, Peruzzi 1999). In a child born at week 33, acute kidney failure was described after oligohydramnios was determined at week 30 and already in the 1st trimester, i.e. before the "sensitive phase" of therapy with nimesulide, diclofenac and paracetamol (Benini 2004). Another case report describes a child with chronic kidney damage after four weeks of nimesulide therapy for the mother from week 30, who was diagnosed with oligohydramnios just 2 weeks after the start of therapy. Conservative therapy was still required at the age of 20 months (Magnani 2004). Holmes and co-workers (2000) Also report on an oligohydramnios, which occurred 3 weeks after a nimesulide therapy for labor prophylaxis started in week 24 and which normalized again after the end of the therapy. The child born ripe was healthy. A similar result was found in a report of 5 pregnancies with nimesulide therapy for preterm labor. All women developed oligohydramnios about 3 days after the start of therapy, which regressed after the end of treatment. None of the children showed any manifest kidney damage (Locatelli 2001). In a prospective study, around half of the 44 women who received nimesulide therapy for the prophylaxis of premature labor developed oligohydramnios after about four weeks of therapy, which regressed again after the end of therapy. In one case of acute kidney failure in the premature baby, the mother failed to attend the prescribed check-ups. In no case was it necessary to discontinue therapy because of occlusion of the ductus arteriosus (Sawdy 2004). Paladini (2005) describes 10 cases with occlusion of the ductus ateriosus in newborns after taking a maximum of 2 single analgesic doses shortly before birth (Paladini 2005).

Other investigators found no side effects in the newborn after tocolysis Sulindac in 10 pregnant women in week 28-32 (Sawdy 2003). Sulindac Due to the low placenta penetration of its active (sulfide) metabolite, it should not have any changes on the fetal circulation that can be detected by Doppler sonography (Carlan et al., 1995, Carlan et al., 1992, Kramer 1995). This preference over other NSAIDs is not confirmed in other publications (Kramer 1999).

Recommendation for practice:

Well-tested NSAIDs such as ibuprofen and diclofenac can be used as analgesics or for anti-inflammatory therapy in the first two thirds of pregnancy. From week 30 onwards, these agents should be avoided. If treatment is nevertheless carried out in late pregnancy, the fetal circulation should be checked regularly (once or twice a week) sonographically for changes in the haemodynamics in the ductus arteriosus and oligohydramnios should be excluded. Tokolysis with prostaglandin antagonists cannot be recommended. After therapy in the 1st trimester, none of these agents requires invasive diagnostics. A risk-based termination of a desired and intact pregnancy is not indicated (see Chapter 1.15).