Maternal Acid-base Status Research Articles

1105: Safety and feasibility of humidified-warmed PACI (partial-amniotic-carbon-dioxide-insufflation) for fetoscopic spina bifida repair

Fetoscopic spina bifida (SB) repair under humidified-warmed Partial-Amniotic-Carbon-dioxide-Insufflation (hw-PACI) is being clinically implemented without preclinical validation, yet with promising preliminary results. We experimentally assessed the safety and feasibility of hw-PACI for fetoscopic anatomical SB repair. We used a standardized skin-defect fetal lamb model (100days). We first performed a 7-8cm-hysterotomy, inserted 2 microcatheters in the fetal carotid artery and under the skin nearby a 4x2cm lumbar skin marking and closed the uterus. Animals were assigned to either veterinary or clinical general anesthesia (GA). Through an exteriorized uterus, we performed a simulated 3-port fetoscopic anatomical watertight-layered repair of the defect under hw-PACI. Primary outcomes were persistent normal pH (pH≥7.23) (safety) and postoperative watertightness of the skin closure in ≥70% of cases (feasibility). Secondary outcomes were fetal and maternal acid-base status, hemodynamics, fetal survival, operation times. Twelve fetuses (one per ewe) were operated by 2 surgeons (pneumo-amnion 5±1mmHg) and survived, 7 in the veterinary and 5 in the clinical GA groups. Compared to baseline, hw-PACI under veterinary GA induced acidosis from 60min onwards (lower pH, 7.00) and hypercapnia from 30min (higher pCO2, 112mmHg); both resolved 30min after stopping PACI at the end of the procedure (Fig.1). In contrast, acidosis and hypercapnia were transient (< 60min) under clinical GA, occurring only at 60min (lower pH, 7.18) and at 60 and 180min (higher pCO2, 90mmHg) respectively (Fig.2). Fetal pO2, base excess, lactate and heart rate as well as maternal hemodynamics and acid-base status remained normal (Fig.1&2). In both grousps respectively, 5/7 (71%) and 4/5 (80%) closures were watertight. Operation times were long and comparable (insufflation: 202±37min vs. 196±25min; fetal repair: 141±34min vs. 145±33min). Following an adequate clinical anesthetic protocol, hw-PACI for fetoscopic SB repair is safe and allows for watertight layered SB closures.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Fetal nucleated red blood cells in a rat model of intrauterine growth restriction induced by hypoxia and nitric oxide synthase inhibition

Nucleated red blood cells (NRBCs) in fetal circulation have been proposed as a marker of chronic hypoxia in fetuses with intrauterine growth restriction (IUGR). We sought to determine the effects of chronic hypoxia, chronic nitric oxide inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME), or both on NRBC counts, erythropoietin levels, and pathologic changes in an animal model of IUGR. We assigned timed pregnant adult Sprague Dawley rats to the following groups: (1) 21% oxygen + saline solution (n = 7); (2) 21% oxygen + L-NAME (n = 8); (3) 10% oxygen + saline solution (n = 6); and (4) 10% oxygen + L-NAME (n = 6). We inserted osmotic pumps that were prefilled with saline solution or L-NAME subcutaneously on day 17 of gestation. The animals were placed in a Plexiglas hypoxic chamber, which ensured a constant hypoxic environment. The animals were killed on day 21 of gestation before the onset of spontaneous labor. We collected maternal and fetal blood for measurement of NRBC and erythropoietin levels. The results were interpreted in relationship to maternal arterial blood gases and hemoglobin and hematocrit levels. Fetuses were examined for gross abnormalities and histological abnormalities that are characteristic of vascular disruptions by a blind examiner to experimental manipulation. Nitric oxide inhibition induced IUGR with maximal effect when both L-NAME and hypoxia treatments were combined. Inhibition of nitric oxide synthesis, but not chronic hypoxia, increased the number of fetal NRBCs and generalized hemorrhagic diathesis in utero. These features were aggravated significantly when the treatments were combined. Moreover, chronic hypoxia induced significant maternal metabolic acidosis and increased hematocrit and erythropoietin levels in maternal and fetal blood. Nitric oxide inhibition increased maternal hematocrit levels while decreasing maternal erythropoietin levels without significantly altering the maternal acid-base status. In contrast with chronic hypoxia, nitric oxide inhibition increased fetal NRBCs without affecting erythropoietin levels. Our findings indicate that the number of NRBCs in fetal circulation does not serve as a specific marker of chronic hypoxia that accompanies IUGR or of elevated erythropoietin levels but are an epiphenomenon that is related to the inhibition of nitric oxide.

Maternal respiration and blood gases during aerobic exercise performed at moderate altitude

We studied whether maternal acid-base status during aerobic exercise performed at moderate altitude is affected by pregnancy. Seven primiparus women were tested at 37 wk gestation and 12 wk postpartum. Subjects were studied at rest, and during two cycle (50 W, 75 W) and two treadmill (67 m.min-1; 2.5% grade, 67 m.min-1; 12% grade) protocols. Exercise bouts lasted 6 min with a 10-min rest between sessions. Minute (VE) and alveolar (VA) ventilation, tidal volume (VT), and ventilatory equivalent for carbon dioxide (VE/VCO2) were significantly (P less than 0.01) greater when exercise was performed during pregnancy. Physiological dead space (VD) was not affected by pregnancy status and did not differ between rest and exercise. Decreases (P less than 0.01) in arterial pH during exercise averaged 0.04 units in both pregnancy and postpartum. Despite similar change in maternal pH, carbon dioxide tension (PaCO2) remained unchanged during exercise at 37 wk gestation but decreased at 12 wk postpartum. Decreases in arterial bicarbonate [HCO3-] associated with exercise were smaller during pregnancy. Our findings indicate that pregnancy did not compromise maternal acid-base status during aerobic exercise.

Maternal acid-base status during cesarean section under thiopental, N2O, and succinylcholine anesthesia

Maternal acid-base status was evaluated in 17 normal term pregnant women undergoing repeat cesarean section under thiopental, nitrous oxide, and succinylcholine anesthesia. Little change in maternal acid-base status was noted during the surgical procedure. The induction and maintenance of anesthesia for operation prior to delivery resulted in a very mild acidosis (pH 7.42 to 7.37) which was due to a slight increase in arterial carbon dioxide tension and a slight decline in bicarbonate. The dosages of thiopental used (2.5 to 4 mg. per kilogram of body weight) did not affect the fetal outcome. However, it appears that prolonging nitrous oxide-oxygen anesthesia at concentrations of 70 to 30 per cent results in a high incidence of fetal depression (Apgar 5 or less at one minute) at delivery but not fetal acidosis as shown by cord blood evaluation. The 5 minute Apgar score in 13 of the 14 newborns recorded was 7 or above. Balanced anesthesia is safe for cesarean section so long as the time from induction to delivery is not prolonged.

Effects of simulated maternal hyperventilation on the umbilical vein

There is some question about the role of hyperventilation in obstetric anesthesia. There are thought to be certain fetal benefits from this alteration in the maternal acid-base status. Certain clinical and animal studies have documented that excessive hyperventilation may lead to deterioration of the acid-base status of the fetus. The etiology of this problem has been thought to be maternal alkalosis with decreased uterine artery blood flow and subsequent inadequate placental perfusion. The object of this study was to determine if there was a fetal component of this problem. This in vitro study of simulated hyperventilation in 22 human umbilical veins demonstrated pressure changes with changes in pH and Pco2. It was observed that for every 0.1 U. pH decrease the vein decreased in pressure by 8.7 per cent, and for every 0.1 U. pH increase the pressure increase was 6.3 per cent. The clinical implications of these studies were discussed.

Maternal acid-base metabolism in normal human parturition

Maternal arterial blood has been obtained serially in labor and analyzed for pH, Pco 2 , and base excess. Prior to and at the onset of labor, hypocapnia has been demonstrated. At 9 to 10cm. of cervical dilatation, a mixed disturbance with metabolic acidosis and respiratory alkalosis has been identified. This change is most marked at the conclusion of the second stage of labor. No demonstrable change in maternal acid-base status could be related to duration of labor when labor did not exceed 17hours. Properly collected maternal capillary samples may be analyzed for pH, Pco 2 , and base excess instead of arterial puncture blood without loss of accuracy.

Fetal acid-base status I. Relationship between maternal and fetal pCO2

In order to understand the control of fetal acid-base status, it is necessary to consider its relationship to the maternal acid-base status. The present investigation was designed to study the relationship between fetal and maternal capillary blood pCO2 during normal labor and following artificial increase and decrease of maternal pCO2. The relationship between fetal heart rate and fetal pCO2 was also investigated. A positive linear relationship between maternal and fetal pCO2 was found and a mathematical expression for this relationship determined. A positive correlation between fetal heart rate and fetal pCO2, was found. Maternal overbreathing lowered fetal pCO2 and carbogen inhalation raised fetal pCO2 The fetal maternal pCO2 gradient was altered during these acute experiments. In 4 patients with fetal hypercapnia, the fetal heart rate pattern showed features consistent with cord compression and in one other patient with marked bradycardia during a contraction a rise in fetal PCO2 occurred during the period of bradycardia.

Maternal acid-base status and neonatal respiratory distress in normal and complicated pregnancies

In order to investigate the possible etiological importance of maternal blood-gas and acid-base status in the respiratory distress syndrome, studies were made on the arterial blood of mothers at delivery and on cord and on 1 hour arterial samples of their infants. A total of 79 maternal samples, 76 cord bloods, and 30 1 hour infant samples were studied. The maternal blood data indicated that neither maternal hypoxia nor acidosis at delivery was etiologycally important in the 14 infants who developed respiratory distress. Moreover, clinical and cord blood biochemical studies also suggested that the presence of intrauterine asphyxia as deduced from such information was not an important etiological factor in this syndrome. Infant arterial samples suggested that maternal metabolic acidosis, when present, was associated with acidosis in the infant which persisted at least 1 hour.