Neurodevelopmetal effects of maternal blood pressure management with noradrenaline during general anaesthesia for nonobstetric surgery in the pregnant rabbit model

Abstract

BACKGROUNDIn pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, the rationale being to maintain uterine perfusion pressure and thereby uterine blood flow. Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent.OBJECTIVETo analyse the effects of treating anaesthesia-induced hypotension with noradrenaline on brain development of rabbit foetuses of mothers subjected to general anaesthesia for nonobstetric surgery. We hypothesised that treatment of maternal hypotension would improve foetal outcomes.DESIGNRandomised controlled laboratory study using 21 pregnant rabbits (does) at 28 days of gestation.INTERVENTIONTwo hours of sevoflurane anaesthesia for a laparotomy without treatment of anaesthesia-induced hypotension (hypotension group) or with maintaining maternal mean arterial pressure above 80% of the awake value using noradrenaline (noradrenaline group). In the control group, does remained untouched. At term, all pups were delivered by caesarean section. One day later, the neurobehaviour of the pups was assessed and brains were harvested.MAIN OUTCOMESNeuron density in the frontal cortex for the comparison of noradrenaline groups versus hypotension groups was the primary outcome; the neurobehavioural scores and other histological outcomes were secondary outcomes.RESULTSIn the noradrenaline groups and hypotension groups, neuron density in the frontal cortex was similar (1181 ± 162 versus 1189 ± 200 neurons mm−2, P = 0.870). However, significantly less foetal survival, lower sensory scores in neurobehavioural assessment and less proliferation were observed in the noradrenaline group when compared with the hypotension group. Neuron densities in other regions, total cell densities, biometrics and synaptogenesis were not affected. There were no differences between the control group and hypotension group.CONCLUSIONDuring general anaesthesia for nonobstetric surgery in rabbits, treatment of anaesthesia-induced hypotension using noradrenaline did not affect neuron densities but was associated with impaired foetal outcomes according to several secondary outcome parameters. Further studies are needed to investigate any clinical relevance and to determine the target blood pressure in pregnant women during general anaesthesia.KEY POINTSIn pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, with the rationale to maintain uterine perfusion pressure and thereby uterine blood flow.Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent.We investigated the effects of treating anaesthesia-induced hypotension with noradrenaline on the brain development of rabbit foetuses, of mothers subjected to general anaesthesia for nonobstetric surgery.We hypothesised that treatment of maternal hypotension would improve foetal outcomes.Neuron densities were similar but significantly less foetal survival, impaired neurobehaviour and less proliferation were observed after treat...

General anesthesia for maternal surgery during pregnancy: dogmas, myths and evidence, a narrative review

“…The most likely explanation for this observation is that noradrenaline reduces uterine blood flow in rabbits 93,94 . Clinical relevance of these observations remains to be investigated 93 .…”

“…In rabbits, several parameters of fetal brain development were impaired and fetal mortality was higher when maternal blood pressure was maintained at ≥ 80% of the awake value using noradrenaline when compared to untreated maternal hypotension 93 . The most likely explanation for this observation is that noradrenaline reduces uterine blood flow in rabbits 93,94 . Clinical relevance of these observations remains to be investigated 93 .…”

“…In contrast to the extensive evidence in the setting of neuraxial anesthesia for cesarean section, evidence on the hemodynamic management during general anesthesia for non-obstetric surgery is nearly absent. The hypothesis that maintaining the maternal blood pressure around the awake value would improve fetal outcome during general anesthesia for maternal surgery was recently tested in a preclinical study 93 . In rabbits, several parameters of fetal brain development were impaired and fetal mortality was higher when maternal blood pressure was maintained at ≥ 80% of the awake value using noradrenaline when compared to untreated maternal hypotension 93 .…”

“…The hypothesis that maintaining the maternal blood pressure around the awake value would improve fetal outcome during general anesthesia for maternal surgery was recently tested in a preclinical study 93 . In rabbits, several parameters of fetal brain development were impaired and fetal mortality was higher when maternal blood pressure was maintained at ≥ 80% of the awake value using noradrenaline when compared to untreated maternal hypotension 93 . The most likely explanation for this observation is that noradrenaline reduces uterine blood flow in rabbits 93,94 .…”

Prenatal anesthetic exposure and offspring neurodevelopmental outcomes—A narrative review

“…Hypotension during anesthesia and surgery can be another confounding factor that affects uteroplacental perfusion and therefore the fetus. In this regard, Bleeser et al ( 18 ) used pregnant rabbits to investigate whether hypotension affects the fetal outcome and the neurodevelopment of the offspring. Pregnant rabbits were randomized into a norepinephrine group (maintaining the mean arterial pressure above 80% of baseline) and a hypotensive group and underwent a 2 h exploratory laparotomy under sevoflurane anesthesia.…”