Intraabdominal Carbon Dioxide Insufflation in the Pregnant Ewe: Uterine Blood Flow, Intraamniotic Pressure, and Cardiopulmonary Effects

Nine Dorset-cross ewes with singleton pregnancies of 120 to 135 days' gestation (full-term at 150 days) were used in this study, which was approved by the Animal Care Protocol Review Committee, University of Saskatchewan, and conducted in accordance with Canadian Council of Animal Care guidelines. The ewes were fasted for 18 h and deprived of water for 8 h before instrumentation and study.

A lumbosacral epidural injection of 10 ml lidocaine hydrochloride with epinephrine (lidocaine with epinephrine 2%; Langford, Guelph, Ontario, Canada) and 0.07 mg/kg xylazine hydrochloride (Rompun; Bayvet Division, Chemagro Ltd., Etobicoke, Ontario, Canada) was aseptically administered. Animals were placed in dorsal recumbency with oxygen (inspired oxygen concentration 1.0) via face mask (5 l/min) and received balanced electrolyte solution (5% dextrose and 10 ml [centered dot] kg sup -1 [centered dot] h sup -1 Ringers) intravenously. After a ventral midline laparotomy, the pregnant uterine horn was identified and a 10-cm hysterotomy incision was made to exteriorize the fetal hindlimb. Using local infiltration with 2% lidocaine and a surgical cutdown, the fetal femoral artery was isolated and catheterized with a 21-gauge over-the-needle catheter. Using the Seldinger technique, a 5-French, 6-cm customized silastic infant feeding tube (Bard Canada, Mississauga, Ontario, Canada) was placed over a pediatric J-wire (central vein catheterization set; Arrow International, Reading, PA) and inserted through the femoral artery into the descending aorta. The infant feeding tube was connected to arterial pressure tubing (Abbott Laboratories, North Chicago, IL) and secured with sutures and adhesive (Vetbond; 3M Canada, Toronto, Ontario, Canada). A 12-French Kaslow stomach tube (Baxter Healthcare Corporation, Deerfield, IL) was placed in the amniotic cavity to monitor IAP. The two pressure catheters were exteriorized through one end of the hysterotomy incision. The fetal surgical site and uterine incision were closed with 2-0 absorbable sutures. A calibrated transit time ultrasonic flow probe (model T201; Transonic Systems, Ithaca, NY) was placed around the uterine artery of the pregnant horn just proximal to the arterial bifurcation. The two intrauterine catheters and the Transonic cable were exteriorized through the ewe's right flank and the laparotomy site was closed. One hundred twenty milliliters of warm saline solution with 500 mg of sodium ampicillin (Penbritin 500; Ayerst Laboratories, Montreal, Quebec, Canada) were infused into the amniotic cavity through the amniotic catheter to replace amniotic fluid lost during the procedure.

After local infiltration and surgical cutdown, the maternal carotid artery was catheterized using a 16-gauge, 14-cm catheter (Angiocath, Becton-Dickinson, Sandy, UT) and attached to noncompliant pressure tubing. An 8-French pulmonary artery catheter introducer (Cordis Introducer, Daig Corp., Minnetonka, MN) was placed and secured in the jugular vein. Postoperative analgesia consisted of 0.2 mg/kg butorphanol tartrate (Torbugesic; Ayerst Laboratories) intramuscularly, after which ewes were returned to their pen. Antimicrobial therapy consisted of 25,000 iu/kg procaine penicillin (Ethacillin; Rogar/STB, London, Ontario, Canada) given intramuscularly and an intraamniotic infusion of 500 mg sodium ampicillin once daily.

The animals were randomized to receive two treatments: insufflation to an intraabdominal pressure of 15 mmHg and no insufflation (controls). No laparoscopic surgery was done.

Ewes were rested for 48 h between implantation and the time of the study. Once the first study was complete, the ewes recovered from anesthesia, rested for 48 h, and then entered the cross-over study.

Before inducing anesthesia, fetal and maternal arterial blood samples were drawn. If fetal acidemia (pH < 7.2) was present, the study was postponed until the fetal pH was normal. After anesthesia was induced with 10 to 15 mg/kg sodium thiopental (Pentothal, Abbott Laboratories, Montreal, Quebec, Canada), the trachea was intubated and the animal maintained at a constant end-tidal halothane (MTC Pharmaceuticals, Cambridge, Ontario, Canada) administered at 1 to 1.5 minimum alveolar concentration (MAC; 1 MAC was taken as 0.78% [11]) and 100% oxygen. Continuous skeletal muscle relaxation was provided with 0.01 mg/kg intravenous vecuronium bromide (Norcuron; Organon Canada Ltd., West Hill, Ontario, Canada) and monitored using a peripheral nerve stimulator (Digi Stim III, Neurotechnology, Houston, TX) placed over the peroneal nerve.

In both insufflation and control groups, changes in mechanical ventilation were made to maintain Pa^CO2between 35 and 40 mmHg. A volume-cycled ventilator (Drager AV Ventilator, North American Drager, Telford, PA) was used to control and maintain ventilation by adjusting tidal volume up to 20 ml/kg and then respiratory rate, guided by intraoperative maternal arterial blood gas analysis. Minute ventilation was obtained from ventilator settings of tidal volume and respiratory rate. Circuit airway peak pressure was measured from the Bourdon gauge of the breathing circuit. Maternal ETCO², end-tidal halothane, and respiratory rate were recorded with a gas analyzer (Ohmeda 5250 respiratory gas monitor; Ohmeda, Louisville, KY).

A 7-French triple-lumen pulmonary artery catheter (Edwards Swan-Ganz catheter; Baxter Corp., Toronto, Ontario, Canada) was advanced through the catheter introducer and positioned in the pulmonary artery to measure cardiac output, pulmonary arterial wedge pressure, mean pulmonary arterial pressure, and central venous pressure. Correct placement was confirmed by observing characteristic pressure waveform. Maternal mean arterial pressure (MAP), pulmonary artery wedge pressure, mean pulmonary artery pressure, central venous pressure, IAP, heart rate (HR), and fetal MAP and HR were recorded with a multichannel computer system (Hewlett-Packard M1092A, Sorrona, Italy). Cardiac output was determined using the thermodilution technique, using 10 ml room temperature 5% dextrose and a cardiac output computer (Gould Hemodynamic Profile Computer SP1445; Gould, Cardiovascular Products Division, Oxnard, CA). Three measurements were averaged and recorded. Blood samples were drawn from the fetus and the maternal carotid and pulmonary arteries to measure blood gases (Copenhagen Radiometer Acid-Base Laboratory 330, Copenhagen, Denmark).

The intraamniotic, fetal, and maternal lines were connected to a pressure transducer computer (Hewlett Packard M1092A) and the Transonic flow cable was connected to a computerized monitor (model T201; Transonic Systems).

Carbon dioxide pneumoperitoneum to a pressure of 15 mmHg was achieved by insufflating carbon dioxide through a Verres needle placed in the supraumbilical area using a standard procedure. An automatic laparoscopic insufflator (SOLOS Endoscopy, Atlanta, GA) was used to monitor the intraperitoneal pressure during insufflation. Baseline measurements were taken 30 min after anesthesia was induced. Data were collected at regular intervals during the 60-min insufflation period and during the first 30 min after desufflation.

Corrected fetal MAP was calculated by subtracting the IAP from the measured fetal MAP. Maternal and fetal heart rate (m-HR, f-HR), maternal MAP, and UBF were measured every 5 min. Central venous pressure, mean pulmonary artery pressure, Pulmonary artery wedge pressure, cardiac output, ETCO², maternal and fetal serum lactate, m-ABG, and f-ABG measurements were taken every 15 min. Respiratory rate, tidal volume, airway peak pressure, fresh gas flow, and IAP were measured every 20 min. All pressures and cardiac output measurements were taken at the end-expiration phase of the respiratory cycle. Percentage of venous admixture, minute ventilation, cardiac index, systemic vascular resistance (dynes [centered dot] cm [centered dot] s sup -5), pulmonary vascular resistance (dynes [centered dot] cm [centered dot] s sup -5), and to ETCO²(Pa^CO2-ETCO²) gradient were calculated using standard formulas. All ewes and fetuses were killed at the end of the study by an overdose of sodium thiopental.

One-way analysis of variance for repeated measures was used for statistical evaluation of the results. A probability value less than 0.05 was considered significant. Differences over time in variables that were significant according to the analysis of variance were examined using the Student's t test for paired observations.

The animal population did not differ significantly from each other in their mean weight (58 +/- 8 kg) or stage of pregnancy (125 +/- 6 days) at the time of surgical instrumentation. One ewe was allowed to rest for an additional 24 h after instrumentation because the fetal arterial pH was 7.2. This animal recovered without complications and completed the cross-over study. All of the variables investigated were normally distributed.

Increases in the Pa^CO2Pa^CO2-ETCO²gradient to a mean maximal value of 16 mmHg (P = 0.04) occurred during insufflation, with values returning to baseline with desufflation. In the control group, the gradient remained constant at approximately 6 mmHg (Figure 1). Decreases in ETCO²were statistically significant (P = 0.0006) during insufflation (Table 1). To maintain maternal normocarbia, an increase in minute ventilation (P = 0.001) was required during insufflation up to 300 ml [centered dot] kg sup -1 [centered dot] min sup -1 (Figure 2). Maternal PaO²decreased significantly (P = 0.02) during insufflation, with a mean minimal value of 137 +/- 35 mmHg. Values returned toward baseline with desufflation (Figure 3.)

Breathing circuit peak pressure increased significantly during insufflation to a mean maximal value of 25 +/- 2.8 cm water (P < 0.001), returning toward baseline with desufflation.

A constant IACO²pressure of 15 mmHg was maintained during insufflation. Statistically significant increases (P = 0.02) in IAP, on average 9 mmHg greater than baseline pressure, resulted during insufflation, whereas values remained constant in the control group (Figure 4).

No significant differences were found between insufflation and control groups with respect to MAP, HR, central venous pressure, pulmonary artery wedge pressure, mean mean pulmonary artery pressure, cardiac index, systemic vascular resistance, pulmonary vascular resistance, UBF, or venous admixture.

Fetal Pa^O2remained within physiologically normal limits in both groups (Table 2). Corrected fetal MAP to account for IAP changes was not different between groups (Figure 5). No significant differences in HR were noted between study groups, nor were there changes in acid-base status (Table 2). There were no fetal deaths and no preterm labor was detected in any of the animals in this study.

Fetal death, [12]spontaneous abortion, and preterm labor [13]have been reported in pregnant patients shortly after undergoing laparoscopic surgery. However, uncomplicated completion of pregnancy after laparoscopic surgery has also been reported. [6,14,15] 

The use of laparoscopic surgical procedures during pregnancy remains controversial. Potential risks include maternal and fetal acid-base disturbances and uteroplacental perfusion alterations secondary to carbon dioxide pneumoperitoneum. Physiologic implications of pregnancy must be considered in addition to the known effects of IACO²insufflation before considering the use of laparoscopic techniques in pregnant women.

Previous studies in pregnant animal models have shown maternal and fetal acidosis and tachycardia using ETCO²-guided ventilation. [10],* In our previous pilot study, [10]maternal acidosis confounded the interpretation of the fetal acidosis. In the present study, Pa^CO2-guided ventilation was used to maintain maternal normocarbia and define the effects of carbon dioxide pneumoperitoneum on fetal acid-base status and maternal cardiopulmonary parameters, UBF and IAP changes.

Precise control of ventilation during the insufflation and early desufflation periods is required to avoid maternal hypercarbia and hypocarbia, respectively. During desufflation, ventilatory parameters must be regulated because hyperventilation can result in decreased UBF, [16]and hypocarbia may increase maternal hemoglobin oxygen affinity with potential detrimental effects on fetal oxygenation. [16,17] 

During carbon dioxide pneumoperitoneum, increased intraabdominal pressure can result in decreased diaphragmatic excursion, reduced pulmonary compliance, and increased deadspace ventilation. [18]In addition, absorption of carbon dioxide from the peritoneal cavity [19,20]can result in increased Pa^CO2unless appropriate ventilatory adjustments are made to eliminate the excess carbon dioxide and overcome the increased deadspace ventilation. [21]The marked increase in the Pa^CO2-ETCO²gradient observed in our study reflects the inadequacy of ETCO²to estimate Pa^CO2accurately.

Decreases in maternal oxygenation probably was a reflection of decreased functional residual capacity and increased ventilation/perfusion ratio mismatch. Despite the decrease in maternal oxygenation, the fetal Pa sub O²remained within normal limits. The absence of fetal acidosis in this model would suggest that fetal acidosis reported in other studies [10]a, has been due to the concurrent maternal respiratory acidosis resulting from ineffective ventilation.

As in other gravid animal studies, [10,22,23],* no significant changes occurred in maternal hemodynamics during a 1-h insufflation period to an intraabdominal pressure of 15 mmHg in dorsal recumbency. Galan and associates [9]reported increases in pulmonary artery wedge pressure, central venous pressure, and mean pulmonary artery pressure at 20 mmHg but not at 10 mmHg insufflation pressure using the gravid baboon model.

In nongravid patients, wide variations in hemodynamic responses to insufflation have been observed. Most studies report an increase in systemic vascular resistance, MAP, and right atrial pressure and a decrease in cardiac index. [24,25]Venous return is reduced when insufflation pressures approach those used in our study. [26]Other studies did not report a significant change in cardiac output, although there was an increase in MAP, central venous pressure, and HR. [27] 

Increased intrathoracic pressure also may develop in pregnant patients during insufflation because of decreased chest compliance as the diaphragm is pushed into the thorax. Although it is an inaccurate reflection of true intrathoracic pressure, circuit pressure was increased significantly in this study during insufflation.

We noted no changes in UBF. In a previous study, [23]carbon dioxide pneumoperitoneum at an intraabdominal pressure of 20 mmHg resulted in pressure-dependent decreased perfusion of the maternal placenta. However, no changes were seen in maternal arterial pressure, fetal cardiopulmonary, or acid-base status.

We observed a significant increase in Pa^CO2-ETCO²gradient during insufflation. A considerable underestimation of Pa^CO2can occur if ETCO²is used to monitor the adequacy of ventilation of pregnant patients undergoing IACO²insufflation. There were no changes in fetal MAP, HR, acid-base status, or serum lactate.

Additional studies investigating delayed fetal effects of IACO sub 2 insufflation, cardiopulmonary effects of patient positioning, and laparoscopic surgery should be done to identify pathophysiologic changes in pregnant women.

The authors thank Dr. Antonio Garcia, Dr. Hugh Semple, Dr. Rachel St. Vincent, Sharon Martin, A.H.T., and the staff of the Animal Care Unit, University of Saskatchewan, Saskatoon, Canada, for technical and professional assistance.

*Hunter J, Swanstrom L, Thornburgh K: Carbon dioxide pneumoperitoneum induces fetal acidosis in a pregnant ewe model. Presented at the 1994 Society of the American Gastrointestinal Endoscopic Surgeons meeting, Nashville, Tennessee, S31:61.