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Gastric Emptying of Water in Obese Pregnant Women at Term

Section Editor(s): Birnbach, David J.Wong, Cynthia A. MD; McCarthy, Robert J. PharmD; Fitzgerald, Paul C. RN, MS; Raikoff, Kiril MS; Avram, Michael J. PhD

doi: 10.1213/01.ane.0000278136.98611.d6
Obstetric Anesthesiology: Research Report
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BACKGROUND: Healthy nonpregnant and pregnant patients may ingest clear liquids until 2 h before induction of anesthesia without adversely affecting gastric volume. In this study, we compared gastric emptying in obese, term, nonlaboring pregnant women (prepregnancy body mass index >35 kg/m2) after the ingestion of 50 and 300 mL of water.

METHODS: Gastric emptying was assessed in 10 obese, term pregnant volunteers using both serial gastric ultrasound examinations and acetaminophen absorption in a crossover study design. After an overnight fast, volunteers ingested 1.5 g acetaminophen and 50 or 300 mL water (randomly assigned) on two occasions separated by at least 2 days. Serial gastric antrum cross-sectional areas were determined using gastric ultrasound imaging and the half-time to gastric emptying (T[1/2]) was calculated. Areas under the plasma acetaminophen concentration versus time curve (AUC), peak concentrations (Cmax), and time to peak concentration (tmax) for 50 mL and 300 mL ingestions were compared.

RESULTS: Mean prepregnancy body mass index was 41 ± 9 kg/m2. Gastric emptying T[1/2] was not different after ingestion of 300 mL water compared with 50 mL (23 ± 11 min vs 32 ± 15 min). There were no differences between acetaminophen AUCs at 60, 90, or 120 min, Cmax or tmax after ingestion of 300 mL compared with 50 mL of water.

CONCLUSIONS: Gastric emptying in obese, nonlaboring term pregnant women is not delayed after ingestion of 300 mL compared with 50 mL of water. Gastric antral volume after ingestion of 300 mL of water is similar to the baseline fasting level at 60 min.

IMPLICATIONS: Findings from this crossover study demonstrate that gastric emptying in obese, term nonlaboring pregnant volunteers did not differ after the ingestion of 50 mL compared with that after 300 mL water. These findings suggest that allowing obese pregnant women to ingest clear liquids may not increase their risk of aspiration.

From the Department of Anesthesiology and Mary Beth Donnelley Clinical Pharmacology Core Facility, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.

Accepted for publication June 1, 2007.

Supported in part by a grant from the Northwestern Memorial Foundation, Chicago, Illinois.

Presented in part at the Annual Meeting of the American Society of Anesthesiologists, San Francisco, California, 2003.

Dr. Cynthia A. Wong, Section Editor for Obstetric Anesthesiology, was recused from all editorial decisions related to this manuscript.

Address correspondence to Cynthia A. Wong, MD, Department of Anesthesiology, 251 E. Huron, F5–704, Chicago, IL 60611. Address e-mail to c-wong2@northwestern.edu.

Reprints will not be available from the author.

Aspiration of liquid and particulate gastric contents into the lungs upon induction of anesthesia is a rare, but serious risk of general anesthesia. Therefore, patients have traditionally been asked to fast overnight to ensure that their stomachs are empty. However, it is often difficult and uncomfortable for patients not to eat or drink, particularly for those scheduled for surgery later in the day. Fasting leads to thirst, hunger, noncompliance, and increased anxiety (1), along with the potential for hypoglycemia and dehydration. Results of studies during the last several decades in healthy, nonpregnant adults, and children have supported the safety of ingestion of clear liquids up to several hours before the induction of general anesthesia (1–6). In 2002, we showed that gastric emptying is not delayed in healthy, term, nonlaboring, nonobese pregnant women after the ingestion of a clear liquid meal (water) compared with remaining nil per os (NPO) after an overnight fast (7).

The Practice Guidelines for Obstetric Anesthesia approved by the American Society of Anesthesiologists' House of Delegates in October 2006 suggest that uncomplicated pregnant women undergoing elective cesarean delivery adhere to the same presurgical fasting guidelines as nonpregnant women (7a), e.g., NPO for clear liquids for 2 h before the scheduled surgical procedure (8). The safety of this practice in the obese obstetrical population has not been well studied, however, and the obstetric guidelines also state that “patients with additional risk factors for aspiration (e.g., morbid obesity …) may have further restrictions of oral intake, determined on a case-by-case basis.”1

The data concerning gastric emptying in the obese population are contradictory. Using radiolabeled food/liquid assessment techniques, various studies have found that gastric emptying of solids and liquids is delayed, unchanged, or more rapid in the obese compared with the lean population (9).

We hypothesized that gastric emptying in obese, term pregnant women after the ingestion of water would not differ from that observed in the same individuals after an overnight fast. The purpose of this study was to compare gastric emptying in obese, term pregnant volunteers after the ingestion of 50 mL water (control) with gastric emptying after ingestion of 300 mL water. We chose 50 mL as the control volume, as opposed to maintaining a strictly NPO status, to ensure that acetaminophen was delivered to the stomach.

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METHODS

Pregnant volunteers provided institutionally approved written informed consent to participate in this crossover study. Exclusion criteria included: systemic disease (other than Type II diabetes mellitus or gestational diabetes mellitus), multiple gestation, prepregnancy body mass index (BMI) <35 kg/m2, use of medications known to affect gastric motility or secretion, and acetaminophen ingestion within 48 h of the study periods. Gastric emptying was determined directly by serial gastric ultrasound examinations (10) and indirectly using the acetaminophen (paracetamol) absorption method (11). The procedures, and the rationale for using ultrasonography and acetaminophen absorption, have been discussed in detail previously (7).

Subjects were studied on two occasions, separated by at least 48 h, between 37 and 39 wk gestation. Subjects fasted overnight and presented for study participation at 0730 h. An IV catheter was inserted into a hand or arm vein. The catheter was attached to a disposable, pressurized, in-line flush system without heparin. This closed system allowed for return of the waste blood to the subject after each blood draw. A blank blood sample was drawn, and baseline ultrasound examination was performed. Study participants then ingested 1.5 g acetaminophen (15 mL liquid suspension acetaminophen) immediately followed by 50 or 300 mL water, the order of which was determined using a random number table. Subjects remained in the semisitting position until completion of the serial ultrasound examinations and were then allowed to sit upright until the last blood sample was obtained.

Ultrasound examinations (Acuson, Mountain View, California; 5 MHz probe) were performed by one of two ultrasonographers who were blinded to the volume of water ingested. The same ultrasonographer performed examinations both times a subject participated in the study. The subjects were positioned in a semiupright position with the head of the bed elevated to 45 degrees (12). The gastric antrum was visualized at baseline (t0), and at 10-min intervals after acetaminophen ingestion for 60 min. Correct identification of the stomach was confirmed by directly observing the entry of the study drug/water into the stomach.

The cross-sectional area (CSA) of two sections of the gastric antrum (distal antrum near the pylorus, antrumpylorus, and proximal antrum, closer to the zone of transition between the corpus and antrum, antrumcorpus) was measured in two sagittal planes (10,13) by the ultrasonagrapher. The maximal anteroposterior and longitudinal diameters were measured, and the CSA for each antral section (corpus and pyloris) was calculated using the formula:

The antrumcorpus and antrumpylorus CSAs at each time point were averaged for further data analysis. The half-maximal CSA (CSA½) was defined as:

The half-time to gastric emptying (T[1/2]) was defined as the time from t0 until the antral CSA area returned to the half-maximal value (14).

Blood was drawn for determination of plasma acetaminophen concentrations immediately before, and every 10 min after the ingestion of acetaminophen and water for 60 min, then every 30 min until 120 min after t0. Plasma acetaminophen concentrations were measured using the high-performance liquid chromatography technique of Ameer et al. (15) except that samples were eluted isocratically at 1.2 mL/min using a mobile phase consisting of methanol-pH 5.29, 0.05 M phosphate buffer in a 15:85 ratio after liquid–liquid extraction, using freshly prepared acetylsalicylic acid as the internal standard. Using 0.25-mL plasma aliquots, this assay had a sensitivity of 0.5 μg/mL with within-day coefficients of variation of 5% or less. Areas under the acetaminophen concentration versus time curve (AUC) were determined at 60, 90, and 120 min by trapezoidal approximation. In addition, peak concentration (Cmax) and time to peak concentration (tmax) were determined.

The primary outcome variable was AUC120. Sample size analysis (α = 0.05, power = 80%) using a two-tailed paired t-test determined that 10 subjects would be necessary to detect a 600 μg · min · mL−1 decrease in acetaminophen AUC120 from a control value of 1800 μg · min · mL−1, assuming a standard deviation of 600 μg · min · mL−1. The control AUC120 in our previous study was 1949 ± 606 μg · min · mL−1 (7). This decrease in acetaminophen AUC has been used as an arbitrarily chosen clinically significant delay in gastric emptying (16).

Antral CSA volumes and acetaminophen AUC values were compared for the control (50 mL) and treatment (300 mL) sessions using ANOVA for repeated measures (session, time). The T[1/2], acetaminophen Cmax and tmax were compared by two-tailed paired t-tests. The criterion for rejection of the null hypothesis was P < 0.05. Data are summarized as mean ± sd.

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RESULTS

Eleven women volunteered to participate in the study. One volunteer did not complete the study because she delivered her baby before the second study session could be conducted; therefore, this subject's data were excluded from the analysis. The characteristics of the remaining 10 study subjects are shown in Table 1.

Table 1

Table 1

Mean antral CSA at times 0–60 min are shown in Figure 1. Gastric volumes at 60 min were not different from baseline. The paired differences in antral CSA (300 − 50 mL) as a function of time are shown in Figure 2. These were not different from each other at any given time. The gastric emptying T[1/2] after ingestion of 300 mL water (23 ± 11 min) was not different from T[1/2] after ingestion of 50 mL (32 ± 15 min) (P = 0.23). The mean decrease and 95% confidence intervals in gastric emptying T[1/2] after ingestion of 300 mL compared with those after 50 mL was 8.4 (−3.4 to 20.4) min.

Figure 1

Figure 1

Figure 2

Figure 2

The results of the analysis of the acetaminophen plasma concentration data are summarized in Table 2. There were no differences between acetaminophen AUCs at 60, 90, or 120 min, acetaminophen Cmax, or acetaminophen tmax after ingestion of 300 mL water compared with those after the ingestion of 50 mL water.

Table 2

Table 2

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DISCUSSION

The important finding of this study is that gastric emptying in obese, term pregnant volunteers did not appear to differ after the ingestion of 50 mL compared with that after 300 mL water. This suggests that fasting guidelines for obese patients scheduled for elective cesarean delivery should not differ from lean patients, and that all women, regardless of BMI, be allowed to consume clear liquids up until 2 h before scheduled surgery. This is important information, as the incidence of obesity is steadily increasing in the pregnant population and obese women are at increased risk for cesarean delivery (17). Other factors besides gastric emptying, however, may influence the risk of aspiration. Obesity is associated with more difficult mask ventilation (18) and intubation (19,20) and difficult airway management is a risk factor for aspiration (21). In addition, the incidence of hiatal hernia and gastroesophageal reflux disease is higher in obese compared with that in lean patients (22). Therefore, obesity may be a risk factor for aspiration during cesarean delivery independent of gastric emptying time.

The critical determinants of morbidity or mortality associated with pulmonary aspiration are gastric volume and pH (23). Several studies in surgical patients have found that fasting gastric volumes, as measured by determining the volume of gastric aspirate, are not different between obese and lean patients (24,25). In the current study, however, the fasting mean (±sd) CSA (518 ± 213 mm2) determined in obese subjects was larger than the mean determined in lean subjects in our previous study (407 ± 255 mm2, mean prepregnancy BMI = 23.1 ± 3.7 kg/m2) (P = 0.02) (7). This, and all subsequent comparisons between the current study in obese women and our previous study in lean women, however, should be interpreted with caution as these were two separate studies. Other investigators compared gastric fluid volume in fasting and nonfasting obese patients scheduled for elective surgery (26). The gastric volume and pH were not different in patients randomized to drink 310 mL clear liquid compared with 10 mL liquid 2 h before scheduled surgery and induction of anesthesia.

Data on fasting gastric pH in obese compared with lean patients are conflicting. Studies have shown no difference (25) and a lower pH in obese patients (24). Although we did not measure pH in our study, it may not be clinically significant because obstetric patients are routinely premedicated with an antacid before the induction of anesthesia for surgical procedures (7a). In any case, gastric volume and pH are intermediate outcome variables, and a larger study is indicated to determine whether liberalizing preoperative fasting guidelines for all term pregnant women, lean and obese, is indeed safe.

The T[1/2] of gastric emptying in our current study population was similar to that found for lean subjects in our previous study using the same methodology (24 ± 6 min for 300 mL and 33 ± 8 min for 50 mL, P < 0.01) (7). Although we found a decrease in T[1/2] of similar magnitude after 300 mL compared with that after 50 mL in the current study, the difference was not statistically significant because of greater variability. The T[1/2] found in the current study was similar to that measured in obese subjects after ingestion of 30–50 mL of radionuclide-labeled water (20.4 min) (27). These investigators also documented marked variability (range, 4–80 min) in half-time to gastric emptying.

Acetaminophen absorption is an indirect method of assessing gastric emptying because acetaminophen passes through the stomach and is absorbed in the intestine (28). Its reliability as a measure of gastric emptying assumes stable pharmacokinetic variables (29). The acetaminophen absorption data in the current study in obese women were markedly different from those in our previous study in lean women (7). The mean AUC120 was approximately one-third that of the lean population. The AUC is directly proportional to the dose of the drug absorbed and inversely proportional to the elimination clearance of the drug. In the present study of obese subjects, Cmax was lower and tmax was later than those observed in our earlier study of lean subjects. These findings are similar to those in another study in which orally administered acetaminophen pharmacokinetics was compared in obese subjects versus lean subjects (30). This observation led the study's investigators to conclude that acetaminophen is absorbed more slowly in obese patients (30). In the context of the present study, this suggests that one reason our obese volunteers had lower AUCs120 is the absorption of less acetaminophen by 120 min compared with the amount absorbed in the lean subjects of our earlier study. Other investigators have compared the pharmacokinetics of IV-administered acetaminophen (to eliminate variability due to variability in absorption) in lean and obese subjects and found a nearly 50% increase in the elimination clearance of acetaminophen in obese subjects (31). This suggests that another reason the obese volunteers of the present study have lower AUCs120 is an increased elimination clearance compared with the lean subjects of our earlier study.

There are several limitations to our study design and results. Our study was under-powered to detect the difference in acetaminophen AUC that we observed. We sampled blood as we had in our earlier study because we did not anticipate slower gastric acetaminophen absorption in obese subjects. Unfortunately, this sampling duration was not long enough to characterize the elimination phase and calculate AUCinfinity in all of the subjects of the present study. Acetaminophen AUCs after 50 mL or 300 mL in the obese subjects of our present study did not differ at 60, 90, and 120 min, nor did those in the lean subjects of our earlier study (7). In addition, the acetaminophen AUCinfinity did not differ between treatments in the lean subjects. Therefore, we have no reason to suspect that AUCinfinity would have differed between treatments in the obese subjects of the present study.

Given the increased variability in T[1/2] in the current study of obese subjects, the study was under-powered to determine a difference in gastric emptying between 300 and 50 mL liquid. A further study limitation is that acetaminophen pharmacokinetics is altered in the obese population, and its use as an indirect measure of gastric emptying has not been validated in this patient population.

Finally, the clinically relevant question is whether term pregnant patients should be allowed to drink clear liquids up until several hours before elective surgical procedures. The finding that gastric emptying of 300 mL water is not prolonged compared with that of 50 mL water does not directly answer this question. Gastric emptying is a surrogate marker for risk of aspiration and increased morbidity. Theoretically, both lean and obese patients could have a large gastric volume at the time of induction of anesthesia, and be at risk for pulmonary aspiration, despite having a fast gastric emptying time.

In summary, we showed that gastric emptying in obese, term, nonlaboring pregnant women is not delayed after ingestion of 300 mL water compared with that after ingestion of 50 mL of water, and that gastric antrum CSA after ingestion of 300 mL of water is similar to the baseline fasting level at 60 min. This finding suggests that allowing obese pregnant women to ingest clear liquids up until several hours before a planned surgical procedure may not increase the risk of aspiration and subsequent morbidity and mortality; however, this remains to be proven.

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