Dehydration and Orthostatic Vital Signs in Women with Hyperemesis Gravidarum

692 ~~ ____ ~ ~

ACADEMIC EMERGENCY MEDICINE AUG 1995 VOL 2/NO 8

University of New Mexico. School of Medicinc. Albuquerque, NM

Oregon Health Sciences University. School of Medicine. Portland. OR

Department of Emergency Medicine

Division of Toxicology. Department of Emergency Medicine

Rcceived: June 9. 1994 Revision received: August 22. 1994 Accepted: August 3. 1994

Address for correspondence and reprints:

David R. Johnson. MD University of New Mexico Department of Emergency Medicine Ambulatory Care Center. 4W Albuquerque. NM 87131

Key words: hyperemesis gravidarum; pregnancy: orthostatic vital signs: tilt test: receiver operating characteristic curves: blood pressure

Dehydration and Orthostatic Vital Signs in Women with Hyperemesis Gravidarum

David R. Johnson, MD, Daniel Douglas, MD, Mark Hauswald, MD, Dan Tandberg, MD

I ABSTRACT

Objectives: To assess the hydration status of women presenting to an ED with hyperemesis gravidarum and to determine whether clinically relevant changes in orthostatic vital signs occur.

Methods: A convenience sample of 23 pregnant women who had hyperemesis gravidarum, with each patient serving as her own control. The study took place in the E D observation unit of an urban teaching hospital. Women who had pregnancies of 5 1 6 weeks’ gestation who had been vomiting for at least 24 hours were included. Supine and standing pulse rates and blood pressures (BPs) were measured sequentially after 5 minutes in each position. Patient weight and urine specific gravity (SG) also were recorded. After 6 L of lactated Ringer’s solution was infused over a 12-hour period, the same measurements were repeated. Pre- and posthydration changes were analyzed using the paired t-test.

Results: The mean treatment weight gain as a percentage of the total body weight was 5.6% 2 2.2% (mean 2 SD). The urine SG de- creased from 1.027 f 0.004 to 1.008 ? 0.003 (p < 0.001). The mean change in systolic BP upon assuming the standing position was - 8.3 ? 12.7 mm Hg before hydration vs 2.9 ? 7.8 mm Hg after hydration (p < 0.001). The corresponding change in mean diastolic BP was 3.7 f 10.9 mm Hg before hydration vs 8.6 2 10.9 mm Hg after hydration (p = 0.12). The mean change in pulse rate upon standing was 26.8 +. 14.5 beatslmin before hydration vs 14.5 2 10.1 beatslmin after hydration (p = 0.002). . Conclusions: Women who present to the ED with hyperemesis gravidarum are significantly dehydrated and experience measurable im- provement in postural pulse rate and systolic BP changes with rehydration. However, the presenting orthostatic changes lack sufficient sensitivity to be effectively used as quantitative screening tests for dehydration.

Acad. Emerg. Med. 1995; 2:692-697.

, . . , . . . . . . . . , . , . . . . . . , . . . , . . . . . . . . . . . . . . . . . . , . . . . . . . . . , , . , . . , . , . , . . . , . . . . . . , . . . . . , . , . . . . , . . . . . . . . . . . . , . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Orthostatic Vital Signs in Hyperemesis Gravidarum. Johnson cr al. 693

I Nausea with accompanying vomiting in early pregnancy is common. If it is not severe, pregnant women who have this symptom complex actually have a lower incidence of spontaneous abortion than do those who do not have these symptoms.’.2 However, when nausea and vomiting are severe and lead to dehydration, in- trauterine growth retardation and lower birth weight may Prior to the widespread use of IV hydration, hyperemesis gravidarum commonly resulted in termination of pregnancies and of maternal death.‘

Although this syndrome likely represents one ex- treme on a continuum, a common definition of hyperemesis gravidarum is: “intractable nausea and vomiting during pregnancy, so severe as to necessitate hospital- i ~ a t i o n . ” ~ Unfortunately, this is a vague definition that does not really help the clinician evaluating subtle alterations of nutritional status, intracellular hydration, and intravascular volume status. A variety of clinical and laboratory findings are thought to provide useful clues to the severity of this syndrome, but few have been evaluated rigorously.

A common bedside test for hypovolemia is the use of orthostatic changes in pulse rate and blood pressure (BP), dso known as the tilt test.6 Interpretation of this test in hypovolemia relies on a rise in heart rate or fall in BP after the patient moves from the supine to the standing position. The merit of orthostatic vital signs for detection of mild to moderate hypovolemia has been

The usefulness of orthostatic vital signs in pregnancy has not been previously studied. We assessed the degree of dehydration in vomiting pregnant patients presenting to an ED by measuring patient weight and urine specific gravity (SG) before and after hydration. We determined the association of presenting postural vital sign changes with degree of dehydration. We also determined whether clinically important changes in postural vital sign changes occur with rehydration.

I METHODS

Study Design This was a prospective, observational study using a

convenience sample of pregnant women presenting to an urban teaching hospital with a chief complaint of persistent nausea and vomiting. Orthostatic changes in pulse rate and BP on initial presentation were compared with the same measurements obtained after a standardized 12-hour period of IV hydration. Each patient served as her own control.

Population and Setting All pregnant women with a chief complaint of nau-

sea and vomiting of at least 24 hours’ duration were

eligible for this study. Patients were included when they had a positive qualitative P-hCG (human chorionic go- nadotropin) determination and pregnancy judged to be of 516 weeks’ gestation by estimated dates and physical examination. An additional inclusion requirement was a urine SG of 21.025, or urinary ketones of 240 mgl dL noted on initial urinalysis obtained upon ED presentation. Patients were excluded when they had other serious medical problems (including presenting serum chemistry abnormalities, as noted below), they had been taking medications (other than vitamins or iron) in the preceding 24 hours, there was evidence of a concurrent infection, or the experimental protocol was violated (discussed below).

The study took place in an urban teaching hospital ED with a volume of 50,000 patients annually. Patients were enrolled in the study after written informed consent was obtained by the attending physician. Each patient was then admitted directly to a six-bed observation unit. No treatment intervention was undertaken until it was determined that the patient met the inclusion requirements and informed consent had been obtained. Patients were enrolled in the study from April 1991 to December 1993. This study was reviewed and approved by the Human Research and Review Committee of the University of New Mexico.

Experimental Protocol An initial laboratory evaluation was carried out in

the ED and included measurement of serum electro- lytes, BUN, creatinine, alanine aminotransferase, total and direct bilirubin, and magnesium. Clinically significant alterations in these studies as determined by the attending physician excluded the patient from the study and necessitated prompt admission to the obstetrics service. The patient’s presenting weight in kilograms was recorded. Heart rate and BP were then measured after 5 minutes in the supine position. These measurements were then repeated after 5 minutes in the standing position.

Intravenous fluids were administered according to a standard protocol. One liter of lactated Ringer’s solution was given over each of the first two hours, then lactated Ringer’s solution with 5% dextrose was given at 500 mL/hour for seven hours. For the last three hours the same fluid was given at a maintenance rate of 167 mlhour . This allowed the infusion of 6 L of fluid in 12 hours. Each patient was kept free of oral intake (NPO) during hours 1-8, was allowed clear liquids during hours 9-11, and was again NPO for the final hour of the protocol. Oral intake and fluid output data were recorded at the discretion of the observation unit nurse. No medication or other intervention was allowed during the study period.

694 ACADEMIC EMERGENCY MEDICINE AUG 1995 VOL 2/NO 8

FALSE POSITIVE FRACTION

I _ _ _ _ Sysltolic BP -----Diastolic BP---PuIsD R ~ D 1

I FIGURE 1. Receiver operating characteristic (ROC) curves for the detection of 2 5 % dehydration. More informative tests are repre- sented by curves that are closer to the top and left boundaries of the graph. The straight diagonal line represents no information. The y- axis represents the true-positive fraction and the x-axis represents the false-positive fraction (1 - specificity). BP = blood pressure.

At the end of the 12-hour study period, a repeat urinalysis was obtained and the patient was instructed to fully empty her bladder. She was again weighed and orthostatic vital signs were measured. Medications were allowed at the end of the study period as dictated by the patient's attending physician. A decision was then made to discharge her, continue hydration in the observation unit for up to 12 more hours, or admit her to the obstetrics service. Though the physicians were not blinded with regard to treatment administered, alterations in the study protocol necessitated study exclu- sion.

Measurements All measurements of pulse rate and BP were made

by the observation unit nursing staff using a Dinamap 8100 vital signs monitor (Critikon, Inc., Tampa, FL). A standardized set of nursing orders was used to ensure uniform data collection. A data collection form was

used to record all study variables. The nursing staff had been previously trained in the use of the vital signs monitor and were informed about the study design and data collection during a series of inservice meetings conducted by one of the investigators.

Data Analysis Changes in systolic BP, diastolic BP, and pulse rate

were analyzed with the paired t-test. The Statgraphics Plus, Version 6 (Manugistics, Inc., Rockville, MD), statistical package was used. All results are reported as the mean 2 SD. A p < 0.05 was considered significant and two-sided tests were used throughout.

Receiver operating characteristic (ROC) curves were calculated for each of the study variables. In relation- ships that have predictive utility, as information in- creases for each test the curve should shift toward the upper left side of the graph (100% sensitivity, 100% specificity) and away from the diagonal line, which in- dicates no apparent information. The area under each curve, therefore, is a measure of the information con- tent of each test.

Hypothesis tests among areas under ROC curves were carried out using parametric maximum likelihood estimates. 'O.'' All ROC statistical calculations were done using FORTRAN algorithms developed by Mew (LABROC1 and CORROC, Metz CE, 1993, Univer- sity of Chicago, Chicago, IL).

I RESULTS

Of 32 patients entered into the study, nine were dropped from the study because complete vital signs were not recorded, leaving 23 subjects for evaluation. The study population ranged in age from 18 to 31 years.

After IV hydration, all women gained weight. The mean weight gain as a percentage of body weight was 5.6 2 2.2%. Urine SG declined in all cases. Mean prehydration SG was 1.027 ? 0.004, compared with 1.008 & 0.003 after hydration (p < 0.001). Table 1 shows the mean changes in pulse rate and BP that oc- curred when the subjects moved from the lying position to standing, during both the pre- and posthydration periods. When the prehydration postural vital sign

4 TABLE 1 Prehydration vs Posthydration Changes in Vital Signs (Mean 2 SD) When Moving from the Lying to the Standing Position . . . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . . . , , , , . , . , . , . . , , , . , . . . . . . . . . . . . . , . . , , . . . . . . . . , , . . , . . . . . . . . . . . . . . . . . . . , . , . . . . . . , , . , . . . . . . . . . . . . . . . . . . . . . . . . , . . . . . . , , . . , . . , . . . . . . . . ,

Postural Change Postural Change before Hydration after Hydration Significance 95% CI

Pulse rate 26.8 -C 14.5 beatslmin 14.5 f 10.1 beatshin p = 0.002 5.2, 19.4

Systolic blood pressure -8.3 f 12.7 mm Hg 2.9 2 7.8 mm Hg p < 0.001 -16.1, -6.4

Diastolic blood pressure 3.7 2 10.9 mm Hg 8.6 2 10.9 mm Hg p = 0.120 -11.0, 1.3

Orthostatic Vital Signs in Hyperemesis Gravidarum, /ohmon et al. 695

changes were compared with the corresponding posthydration values, significant differences were noted for pulse rate and systolic BP, but not for diastolic BP.

The assumption was made that all the women were fully hydrated at the end of the 12 hours of IV fluids, to calculate dehydration as a percentage of total body weight. On the basis of percentage of body weight gained, 20 of the 23 patients (87%) were 23% dehydrated, while nine of the 23 (39%) were 2 5 % dehydrated.

Figure 1 shows the ROC curves for each orthostatic vital sign for detection of dehydration of 2 5 % total body weight. Only a drop in systolic BP and a rise in pulse rate were found to provide significant information gain (p < 0.001 and p = 0.01, respectively).

The areas under each curve were: 0.84 & 0.07 for systolic BP, 0.61 -+ 0.09 for diastolic BP, and 0.70 & 0.09 for pulse rate. Of the three variables, only systolic and diastolic BPs were significantly different from each other (p = 0.013).

Table 2 shows the sensitivity and specificity of each of the vital sign changes to detect a 2 5 % fluid deficit. These calculations were based on the assumption that nine of the 23 patients were 25% dehydrated. No cutoff achieved a sensitivity of 280%.

I DISCUSSION

Nausea and vomiting complicate approximately 70% of pregnancies.2 The degree of dehydration and the usefulness of orthostatic vital signs in the evaluation of these patients in an ED setting have not been previously studied. In this study, we describe some of the clinical characteristics of pregnant women who present to an urban ED with nausea and vomiting.

Previous studies have attempted to evaluate the usefulness of orthostatic vital signs in other populations, with conflicting result^.^.*.^ Currens studied a group of 1,OOO healthy men and women during routine physical examinations and found wide variations in pulse rate and BP when the patients moved from the lying to the standing position.l2 A more recent study by Koziol- Mchin et al. in an ED population revealed similar finding^.'^

In 1947, Green and Metheny showed that for subjects who had been phlebotomized 1,OOO mL of blood, changes were noted when these subjects were passively tilted on a table to 750.14 Other authors have evaluated the ability of orthostatic vital signs to detect acute blood loss. Knopp et al. showed, in a group of healthy blood donors, that a pulse rise of 230 beatdmin or the pres- ence of severe symptoms had a sensitivity of 98% for detection of a 1,000-mL acute blood loss. However, this threshold was not sensitive in detecting a 500-mL blood loss. Blood pressure was not useful in either group.6 Similarly, Baraff and Schriger found that although pulse

.............................................................................................................

I TABLE 2 Sensitivity and Specificity (96) of Pulse Rise and Blood Pressure (BP) Drop to Detect a 2 5 % Fluid Deficit ................................................................................................................

Sensitivity Spccificlty

Pulse > 20 beatslmin Pulse > 25 beatshin Pulse > 30 beatshin

64.3 53.1 57.1 65.6 42.9 75.0

Systolic BP > - 5 mm Hg 78.6 59.4 Systolic BP > - 10 mm Hg 50.0 78.1 Systolic BP > -20 mm Hg 28.6 81.3 Diastolic BP > - 10 mm Hg 14.3 78.1

Pulx > 20 beatshin or systolic 71.4 46.9 B P > - 1 0 m m H g

rise was more sensitive than BP in detecting a 450-mL blood loss, no parameter was sufficiently sensitive to be clinically usefuLn In addition, their study showed no significant difference in orthostatic responses with age.

However, studies of acute blood loss may not be comparable to studies of gastrointestinal (GI) fluid loss. In acute blood loss, intravascular volume depletion pre- dominates, whereas in dehydration, volume loss is spread across all compartments. Therefore, intravascular volume may be relatively spared.

Fuchs and Jaffe found that measuring orthostatic vital signs in a pediatric population was useful for detecting hypovolemia from GI fluid loss. Their study showed that pulse rise was predictive of those who had a fluid deficit as determined by a volume depletion scoring system. l5 However, their volume depletion scoring system was subjective and had not been previously validated.

Finally, Levitt et al. studied a heterogeneous population of adults presenting to an urban ED with com- plaints suggestive of dehydration or occult blood loss. They found a large variation in orthostatic vital signs in both the study and the control population^.^ They were able to show a statistically significant postural difference in systolic BPs only in the group who had suspected blood loss. However, this difference was not large enough to be considered clinically useful.

In our relatively homogeneous study population of pregnant women who had experienced vomiting, we found statistically significant and clinically important differences in orthostatic vital signs, which improved significantly with rehydration. Even though pregnancy is associated with changes in the cardiovascular system, our findings were similar to those for nonpregnant subjects in that a significant increase in pulse rate was found in these dehydrated patients6 In addition, we found a significant drop in systolic BP in our dehydrated patients when they assumed the standing position. In fact, ROC curves for each of the vital signs indicated that a

6% ACADEMIC EMERGENCY MEDICINE AUG 1995 VOL 2/NO 8

drop in systolic BP may yield more information re- garding hydration status than does a change in diastolic BP or an increase in pulse rate. A post-hoc sample size estimate suggests that at least 50 patients would have been required to show a statistically significant change in diastolic BP.

None of the various vital sign change cutoffs used in our ROC curve analysis achieved a sensitivity of r80%'€6hiehydration 25% of total body weight. This finding supp-, the observation that orthostatic vital signs are quite variable between individuals. Hence, we are in agreement with those authors who have con- cluded that this bedside procedure is not sensitive enough to be used as a screening test for hypov~lemia.~,~

The fact that we were unable to find a cutoff that had sufficient sensitivity and specificity for these measurements to stand alone as reliable predictors of hypovolemia should not be surprising. It is likely that most physical findings and bedside procedures fall short of being perfect predictors of any given condition when taken alone. Given our data and the existing literature, it is perhaps more appropriate to use orthostatic vital signs as supplemental clinical information in the as- sessment of potentially hypovolemic patients and a monitor of rehydration success rather than as an iso- lated screening test. The fact that this test is inexpensive and easy to perform also argues for its continued use so long as it is interpreted in the context of the entire clinical picture.

LIMITATIONS AND FUTURE QUEsTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , , . . . . . . . . . . . . . . . . .

As with earlier studies of orthostatic vital sign changes, there is no reliable and easily measurable criterion standard to detect hypovolemia or dehydrat i~n.~ Our study population was defined primarily by patient history and urinary SG. The fact that all of these patients gained weight and showed significant declines in urinary SG supports our contention that they were all dehydrated. However, the amount of weight gain may not be an accurate indicator of the degree of dehydration.

The use of a convenience sample may have intro- duced some selection bias. However, consecutive sam- pling was not possible since both patients and physicians alike had the opportunity to opt for shorter periods of hydration than the 12 hours required by our protocol. In addition, there were times when the observation unit was full and patients could not be entered into the study.

As others have suggested, it is possible that larger changes in postural vital signs would have been noted in a more volume-depleted patient population.6.8 It is interesting that none of our patients became sufficiently symptomatic in the standing position to preclude the measurement of vital sigds. Since this test is influenced primarily by intravascular volume depletion, it may be

more sensitive in detecting acute blood loss as opposed to gradual dehydration from GI fluid losses over several days. The 5-minute delay in measuring vital signs in the standing position was selected arbitrarily; there is a wide variability in delay times reported in the literature.' This time frame is relatively long in comparison with those of other studies and may have dampened the orthostatic changes s ~ m e w h a t . ~ - ~

We used a Dinamap oscillometric BP monitor to prevent observer bias and potential differences in tech- niques between observers. One study has indicated that this method can overestimate systolic BP when compared with random-zero sphygmomanometry. The cor- relation between these two methods was good and the degrees of reproducibility were comparable. l6 Others have found the two methods to be comparable. l7

The diagnosis of hyperemesis gravidarum is poorly standardized. As it is commonly defined, this diagnosis implies hospital admission. It is likely that without well- defined clinical parameters, admitting practices vary greatly among physicians. It is therefore possible that in the absence of a study protocol, several of our patients might have been treated in the ED and released.

This study focused on an ED population of pregnant women who had vomiting and moderate dehydration. It might be useful to look at whether larger changes in orthostatic vital signs occur for those patients who are more severely dehydrated. Such an investigation might evaluate patients who are admitted to the hospital for more prolonged rehydration. However, the widespread availability of IV fluid therapy in outpatient settings for the avoidance of progression to Severe dehydration would limit patient enrollment.

In this study, each woman served as her own control. While this is a useful technique, we could not be sure that all patients were fully hydrated at the end of the study protocol. Although none of the patients returned within 24 hours of discharge, some of them remained in the observation unit for further hydration after the initial 12-hour study period. Simultaneous evaluation of pregnant women who are not vomiting and are not suspected of dehydration as a control group may further clarify the usefulness of orthostatic vital signs as a measure of dehydration status.

Finally, it is possible that obtaining multiple data points, rather than just vital signs before and after hydration, would have yielded useful information regard- ing hydration during treatment.

I CONCLUSIONS

Women who present to the ED with hyperemesis gravidarum are often moderately to severely dehydrated. Clinically important abnormalities in orthostatic pulse rate and systolic BP can be found in such a population.

~ ~ ~~ ~ ~~ ~~ ~ ~

Orthostatic Vital Signs in Hyperemesis Gravidarum, Johnson ct al. 697

However, these presenting abnormalities are of insuf- ficient sensitivity and specificity to be used alone as reliable indicators of dehydration. Nonetheless, im- provement in orthostatic vital sign changes can serve as useful indicators of volume rehydration.

I REFERENCES 1. Weigel RM, Weigel MM. Nausea and vomiting of early preg-

nancy and pregnancy outcome. A meta-analytical review. Br J Obstet Gynecol. 1989; %:1312-8.

2. Weigel MM, Wcigel RM. Nausea and vomiting of early pregnancy and pregnancy outcome. An epidemiological study. Br J Obstet Gynecol. 1989; %:3304- 11.

3. Gross S, Librach C, Cecutt A. Maternal weight loss associated with hyperemesis gravidarum: a predictor of fetal outcome. Am J Obstet Gynecol. 1989; 160906-9.

4. Fitzgerald JE, Webster A. Hyperemesis gravidarum: a clinical study of 3% cases. Am J Obstet Gynecol. 1938; 36:460-6.

5. Abell TL, Riely CA. Hyperemesis gravidarum. Gastroenterol Clin North Am. 1992; 21:835-49.

6. Knopp R. Claypool R, Leonardi D. Use of the tilt test in measuring acute blood loss. Ann Emerg Med. 1980; 9:29-32.

7. Williams TM. Knopp R. The clinical use of orthostatic vital signs. In: Roberts JR, Hedges JR (eds). Clinical Procedures in Emer- gency Medicine. Philadelphia: W. B. Saunders, 1991, pp 445-9.

8. Baraff U. Schriger DL. Orthostatic vital signs: variation with

age, specificity. and sensitivity in detecting a 450 mL blood loss. Am J Emerg Med. 1992; 10:99-103.

9. Levitt MA, Lopez B, Lieberman ME, Sutton M. Evaluation of the tilt test in an adult emergency medicine population. Ann Emerg Mcd. 1992; 21:713-8.

10. Dorfman DD, Alf E. Maximum-likelihood estimation of parameters of signal-detection theory and determination of confidence intervals-rating method data. J Math Psychol. 1969; 6:487-96.

I I . Metz CE. Kronman HB. Statistical significance tests for binormal ROC cuwcs. J Math Psychol. 1980; 22218-43.

12. Currens JH. A comparison of the blood pressure in the lying and standing positions: a study of five hundred men and five hundred women. Am Heart J. 1948; 39646-54.

13. Koziol-Mclain J, Lowenstein SR, Fuller B. Orthostatic vital signs in emergency department patients. Ann Emerg Med. 1991; 20:606- 10.

14. Green DM. Metheny D. The estimation of acute blood loss by the tilt test. Surg Gynecol Obstet. 1948; 8:145-50.

15. Fuchs SM, Jaffe DM. Evaluation of the "tilt test" in children. Ann Emerg Med. 1987; 16:386-90.

16. Manolio TA, Fishel SC, Beattie C, et al. Evaluation of the Dina- map continuous blood pressure monitor. Am J Hypertens. 1988;

17. Silas JH. Barker AT, Ramsay LE. Clinical evaluation of Dina- map 845 automated blood pressure recorder. Br Heart J. 1990;

1:1615-75.

43:202-5.

Documents

Dehydration and Orthostatic Vital Signs in Women with Hyperemesis Gravidarum