Volume of Ipecac-Induced Emesis As a Function of the Volume

Home , Syrup of ipecac

VOLUME OF IPECAC-INDUCED EMESIS AS A FUNCTION OF THE VOLUME

OF FLUIDS ADMINISTERED

Ellen Fassmann Jarvis

A project submitted to the faculty of the

University of Utah In partial fulfillment of the requirements

for the degree of

Doctor of Pharmacy

College of Pharmacy

University of Utah

March 1985 •I

UNIVERSITY OF UTAH COLLEGE OF PHARMACY

FINAL READING APPROVAL

TO THE DOCTOR OF PHARMACY COMMITTEE OF THE UNIVERSITY OF UTAH COLLEGE OF PHARMACY:

I have reed the clinical research project report of Ellen Fassmann Jervis In Its final form and have found that 1) its format, citations, and bibliographic style are consistent and acceptable; 2) its illustrative materials including figures, tables and charts are in place; and 3) the final manuscript Is satisfactory to the Supervisory Committee and is ready for submission to the Doctor of Pharmacy Committee.

Date

Approve acy Practice

Chairman

Approved for the Doctor of Pharmacy Committee

Chairman, Doctor of Pharmacy Committee UNIVERSITY OF UTAH COLLEGE OF PHARMACY

FINAL READING APPROVAL

TO THE DOCTOR OF PHARMACY COMMITTEE OF THE UNIVERSITY OF UTAH COLLEGE OF PHARMACY:

I have read the clinical research project report of Ellen Fassmarm Jarvis In Its final form and have found that 1) its format, citations, arid bibliographic style are consistent and acceptable; 2) its illustrative materials including figures, tables and charts are in place; and 3) the final manuscript is satisfactory to the Supervisory Committee and is ready for submission to the Doctor of Pharmacy Committee.

Approve acy Practice

Chairman

Approved for the Doctor of Pharmacy Committee

h^k /km< lairman, Doctor of Pharmacy Committee UNIVERSITY OF UTAH COLLEGE OF PHARMACY

SUPERVISORY COMMITTEE APPROVAL

of a clinical research project report submitted by

Ellen Fassmann Jarvis

We, the undersigned have read this clinical research project report and have found it to be of satisfactory quality for a Dxtor of Pharmacy Degree.

3Jltfe Date Cnairmen, Supervisory Committee

liti/nr Date ember, Supervisory Committee

Date Member, Supervisory Comm Ittee ACKNOWLEDGEMENT

I would like to thank the members of my Supervisory Committee, John Bosso, Pharm.D.,

Joseph Veltri, Pharm.D., and Douglss Rollins, M.D., PhD. for their guidance and help in the preparation of this manuscript. A special thanks goes to Tom Jennison for his help with the statistical analysis of this study and the University of Utah Hospital Emergency Department for the use of their facilities. TABLE OF CONTENTS

LIST OF TABLES vi

LIST OF FIGURES vii

INTRODUCTION AND OBJECTIVES 1

SUBJECTS 2

METHODS , 3

RESULTS A

Other data collected 5

DISCUSSION 6

CONCLUSION 8

TABLES 10

FIGURES 1?

APPENDIX 1 23

APPENDIX 2 26

REFERENCES 28

CURRICULUM VITAE 30 LIST OF TABLES

Eags

Table I. Subject characteristics : ... 11

Table 2. Time to onset of vomiting, number of single and major vomiting episodes, duration, and volume of ipecac-induced emesis with differing amounts of water 12

Table 3. Time between vomiting episodes, ml/ single episode, and ml/major episode of ipecac-induced emesis with differing amounts of water 13

Table 4 Comparison between the first and second phases in Group 1 and the first and second phases in Group 2 14

Table 5. Comparison between subjects given 8 ounces of water first and subjects given 8 ounces of water second 15

Table 6. Comparison between subjects given 16 ounces of water first and subjects given 16 ounces of water second 16

vi LIST OF FIGURES

Figure 1. Volume {ml) of ipecac-induced emesis with differing amounts of water

Figure 2, Time to onset (min) of ipecac-induced emesis with differing amounts of water

Figure 3. Number of single vomiting episodes of Ipecac-induced emesis with differing amounts of water

Figure 4, Number of major vomiting episodes of ipecac-Induced emesis with differing amounts of weter

Fgiure 5. Duration of vomiting (min) of ipecac-induced emesis with differing amounts of water

vii INTRODUCTION AND OBJECTIVES

Ipecac syrup is the emetic of choice for decontamination of the stomach in many drug overdoses and poison ingestions. Introduced into Europe from its native South America in the 17th century, ipecac (ipecacuanha, "Brazil Root") W8S used as a secret remedy for dysentery until

France's King Louis XIV bought the secret and introduced the formula into the public domain.1

Ipecac is derived from the dried root of Cephaelis ipecacuanha or C. acuminata, plants indigenous to

Brazil and Central America, and cultivated 1n India and Malaysia.2 The active emetic principles in

Ipecac have been identified as the alkaloids, emetine and cephaeline.3 Cephaeline produces greater

nausea and vomiting than emetine, but emetine, which constitutes one third to one half of the total alkaloids in ipecac, is more toxic to the heart and other organs.3 Ipecac also contains the alkaloid

psychotrlne which is believed to be less active and less toxic than the other two alkaloids.3

Ipecac is used as an emetic iri the United States in the form of ipecac syrup USP. Ipecac syrup is

inexpensive, readily available, easy to use, and relatively f8st acting.4"7

The emetic action of ipecac fs thought to be the result of its centrally mediated emetic action accompanied by Its local Irritant action on the gastrointestinal tract. Evidence supporting the centrally mediated emetic action of ipecac syrup includes the work of Thumas which showed that local application of emetine in the area of the medulla produced vomiting in dogs,8 Eggleston and

Hatcher later reported that emetine and cephaeline caused vomiting movements and symptoms of

nausea in animals whose stomachs were completely removed.9 Evidence supporting a gastrointestinal irritant effect of ipecac includes the work of Weaver and Griffith.10 These

investigators demonstrated that early vomiting (within 30 minutes) is due to the direct action of

ipecac on the gastrointestinal tract and that late vomiting (vomiting occurlng 30 minutes or more 2 after administration of ipecac syrup) is a result of centrally induced vomiting. This evidence suggests that the mechanism of ipecac is twofold: a direct irritation of the gastrointestinal mucosa to initiate vomiting and stimulation of the chemoreceptor trigger zone to help propagate the emetic response.

The oral administration of fluids, given immediately prior to or immediately after the ipecac ayrup, is thought to be of some clinical importance as an enhancement of emesis. Anecdotal information suggests that greater amounts of fluid taken by the patient concurrently with ipecac syrup produces more effective emesis. Wood and Bache in 1858 stated that the procedure "is facilitated by and rendered milder by giving fluid just after the syrup. About 200 ml of water or clear fluid should be given".11 In 1975 Arena advised: "The patient should also be given fluid

(1 to 2 glasses) several minutes after the ipecac is swallowed, since emesis may not occur if the stomach is empty".12 In 1980 King observed: "The oral administration of fluids, given just before or after the ipecac syrup, is of utmost importance In effectively inducing emesis."2

Current widely accepted recommendations call for the administration of 2-4 ounces of clear fluids for infants 6 to 11 months old, 4-8 ounces of clear fluids for children 1 to 6 years old, and 8-16 ounces of clear fluids for persons 7 years and older 2 However, these current recommendations are empiric aid have not been clinically tested for effectiveness.

The objective of this study was to determine if a relationship exists between volume of fluids taken with ipecac syrup and volume of emesis produced.

SUBJECTS

Twenty volunteers were recruited to participate In the study. The volunteers were paid for their participation, and each volunteer signed a consent form (Appendix 1) approved by the

University of Utah Institutional Review Board. 3

Volunteers were included in the stud/ if they were at least 18 years of age, currently healthy and free of chronic disease, and had a physical examination within 12 months prior to participation in the stud/. Volunteers were excluded from the stud/ if they were pregnant, taking any chronic medications other than birth control pills, or if they had a blood pressure or pulse which were not within normal limits prior to participation in either phase of the stud/.

METHODS

Each test session involved one subject, the investigator, and a trained observer-assistant.

Arrangements were made with the University of Utah Hospitdl Emergency Department for use of their facilities. A physician was available at all times within the Emergency Department throughout each session.

Vomiting was induced in each subject on two occasions separated by at least one week. The subjects were instructed to take nothing by mouth, solid or liquid, for at least eight hours prior to each session and remained seated throughout each session. For each session, the subject was induced to vomit by administering 30 ml of ipecac syrup and a measured amount of water. The vomitus from each subject was collected and measured by two independent observers, the

investigator and a trained assistant. Both measurements were recorded. The average of the

measurements was used as the volume of vomitus for analytical purposes. The time to onset of vomiting, the number of single and major vomiting episodes, and the duration of vomiting were also recorded for each subject (Appendix 2). For this stud/, a single vomiting episode was defined as an abdominal convulsion which resulted in the expulsion of material from the subject's mouth.

A major vomiting episode was defined as several single vomiting episodes occurlng in rapid succession followed by 8 period of time when the subject reported that he/she no longer felt nauseous. Subjects were advised to take nothing by mouth for two hours following the last 4 vomiting episode. Esch subject was contacted by the principal investigator as a follow-up within

24 hours of each testing episode to determine if any side effects had occurred.

Subjects were divided into two groups by use of a random numbers table. Group 1 was given

30 ml ipecac syrup with 240 ml (8 ounces) water at ambient temperature, and Group 2 was given 30 ml of ipecac syrup and 480 ml (16 ounces) of water at ambient temperature. The groups were then crossed-over, and the amount of water given with the ipecac syrup was switched between the two groups.

In accordance with the objective of the study, the volume of vomitus was analyzed by a two-tailed Student's t-test with 8 level of significance 8t the p<0.05 level for paired data to determ ine if there is a statistically significant difference in the volume of vomitus produced with differing amounts of water. For academic interest, a stepwise multilinear regression analysis with a level of significance at the p<0,05 level W8S also performed on all the data gathered in this study.

RESULTS

Twenty subjects entered the study. Three subjects had to be dropped from the study and were not included in the statistical analysis (Table 1). One subject experienced vomiting and diarrhea lasting approximately eight hours and painful stomach cramps lasting approximately two days and declined to participate in the second phase of the study. Another subject was unable to swallow the ipecac syrup during the second phase of the stud/, and the third subject was subsequently found to suffer from chronic headaches, an exclusion criterion of the study (chronic disease).

The average volume (±SEM) of emesis with 8 ounces of water and 1 ounce of ipecac syrup was 350 ± 15.8 ml. When 16 ounces of water and 1 ounce of ipecac syrup were given, the average volume of emesis was 548 ± 15.5 ml (Table 2, Figure 1). The difference in volume returned was significant (p<0.05) using a two-tailed Student's t-test for paired date.

Other Data Collected

Other data gathered for each subject during the course of this study Included time to onset of vomiting, number of single and major vomiting episodes, and duration of vomiting (Table 2). The average time to onset of vomiting (±SEM) with 8 ounces of water was 19 ± 2.4 minutes as compared to 15 ± 1.5 minutes with 16 ounces of water (Table 2, Figure 2). The average number of single vomiting episodes (±SEM) with 8 ounces of water was 22 ± 3.2 compared to 19 ± 1.8 episodes with 16 ounces of water (Table 2, Figure 3). The average volume of emesis per single vomiting episode USEM) with 8 ounces of water was 22 ± 2.9 ml and 3? ± 4.6 ml with 16 ounces of water (Table 3). The average number of major vomiting episodes (±SEM) with 8 ounces of water was 5.0 ± 1.0 and 4.0 ± 0.46 with 16 ounces of water (Table 2, Figure 4). Subjects' nausea would disappear for an average of 9.7 ±1.1 minutes with 8 ounces of water or 10 ± 1.6 minutes with 16 ounces of water before the next major vomiting episode (Table 3). The average volume of emesis per major vomiting episode was ! 10 ± 19.2 ml with 8 ounces of water and 149

± 17.0 ml with 16 ounces of water (Table 3). The average duration of emesis (±SEM ) with 8 ounces of water was 41 ± 7.0 minutes and 45 ± 5.0 minutes with 16 ounces of water

(Table 2, Figure 5).

Using a stepwise multilinear regression analysis, the only variable which contributed significantly to the total volume of vomitus produced was the amount of fluids administered with the Ipecac syrup (p < 0.05). volume of emesis was 548 ± 15,5 ml (Table 2, Figure 1), The difference in volume returned was significant (p<0.05) using a two-tailed Student's t-test for paired data.

Other Data Collected

Other data gathered for each subject during the course of this study included time to onset of vomiting, number of single and major vomiting episodes, and duration of vomiting (Table 2). The average time to onset of vomiting (±SEM) with 8 ounces of water was 19 ± 2.4 minutes as compared to 15 ± 1.5 minutes with 16 ounces of water (Table 2, Figure 2). The average number of single vomiting episodes (±SEM) with 8 ounces of water was 22 ± 3.2 compared to 19 ± 1,8 episodes with 16 ounces of water (Table 2, Figure 3). The average volume of emesis per single vomiting episode (±SEM) with 8 ounces of water was 22 ± 2.9 ml and 3? ± 4.6 ml with 16 ounces of water (Table 3). The average number of major vomiting episodes (±SEM) with 8 ounces of water was 5.0 ± 1.0 and 4.0 ± 0.46 with 16 ounces of water (Table 2, Figure 4). Subjects' nausea would disappear for an average of 9,7 ± 1.1 minutes with 8 ounces of water or 10 ± 1,6 minutes with 16 ounces of water before the next major vomiting episode (Table 3). The average volume of emesis per major vomiting episode was 110 ± 19.2 ml with 8 ounces of water and 149

± 17.0 ml with 16 ounces of water (Table 3). The average duration of emesis (±SEM ) with 8 ounces of water was 41 ± 7.0 minutes and 45 ± 5.0 minutes with 16 ounces of water

(Table 2, Figure 5).

DISCUSSION

This study W8s designed to answer a fundamental question concerning the relationship between the volume of fluids with ipecac syrup end the volume of the resulting emesis. The results of this study indicate that there is a relationship between administration of differing amounts of fluids with ipecac syrup and the volume of emesis. Sixteen ounces of water produced a volume of emesis that was significantly greater than the volume of emesis produced following 8 ounces of water (p<0.05),

Wh ile it appears intuitively logical that greater amounts of fluids given with ipecac syrup should result In greater volumes of vomitus, this may not necessarily be true. The volume of vomitus in cases of ipecac-induced emesis may be primarily due to the action of the emetic, rather than the volume of fluids administered, If this were the case, then administering the same volume of ipecac with differing amounts of fluids would yield the same volume of vomitus.

A stepwise multilinear regression analysis was performed on all the data gathered tn the study. However, because of the small number of subjects in this study, differences between variables must be large in order for differences to be statistically significant. While no statistical significance was found relating volume of vomitus produced and time to onset of vomiting, this latter variable could influence the final volume of vomitus. Water may be absorbed during this time and be unavailable for emesis. Since most water absorption occurs in the colon, predominantly in the cecum,13 it would be necessary for a significant volume of water to leave j the stomach prior to the onset of vomiting in order to significantly effect the volume of induced i emesis, |

A subjective observation made by all participants in the study was that the second phase of j the study "felt easier on the stomach". This observation occurred regardless of the amount of fluid 1 taken during the second phase. Because of the possible influence of the subjects' "experience" with vomiting during the second phase, Group 1 (subjects given 8 ounces of water first) was compared to Group 2 (subjects given 16 ounces of water first). The average number of single and major vomiting episodes and average duration of vomiting decreased during the second phase of the study for both groups (Table 4). These two factors were probably most influential in contributing to the subjective feelings of the subjects. The subjects* physiological and psychological disposition may have changed because of their experience with Ipecac. Emetine and cephaellne, the most abundant alkaloids in ipecac syrup, re erratically absorbed following oral administration in human volunteers." The half-life of emetine following deep subcutaneous or intramuscular injection is 40-60 days.'"5.'16 Thehalf-lifeofcephaeline is not known. All subjects except three were separated from the two phases by seven days, Subject I was separated from the two phases by 26 days, subject 11 by 17 days, and subject 4 by 12 days, Erratic absorption of the ipecac alkaloids and the long half-life of emetine may have caused a physiological change which affected their reponse during the second phase of the study. Vomiting is an experience that most people find extremely unpleasant, Psychologically, the subjects may have felt less anxious about

Ipecac's effects during the second phase of the study. These factors may have accounted for some of the differences between the groups in number of single vomiting episodes and duration of vomiting which were observed. This observation, however, is not cllncally relevant since patients in poisoning situations are given Ipecac on only one occasion.

Also of interest is the comparison of subjects who received 8 ounces of water for the first phase and subjects who received 8 ounces of water for the second phase (Table 5), A similar comparison was made between subjects receiving 16 ounces of water for the first phase and subjects who received 16 ounces of water for the second phase (Table 6). The average values for time to onset of vomiting, number of single and major vomiting episodes, duration of vomiting, and

volume of vomitus between the groups for the 16 ounce test are reasonably similar. However, the

average values for these same categories between the groups for the 8 ounce test re quite

different. Because the subjects were randomly assigned to the order in which the 8 ounces and 16

ounces of water were given, this difference is unlikely an artifact of the data gathering process but

may be the result of the coveriance of the data.

Toxicity from ipecac alkaloids may Involve the cardiovascular or neuromuscular systems,

the gastrointestinal tract, as well as prolonged vomiting, aspiration of vomitus, and bloody

diarrhea.17-22 However, clinically significant toxicity from the use of this emetic drug is

unusual and has most often occurred as a result of intentional ipecac overdose, inappropriate administration at home, or Inadvertent administration of fluid extract of ipecac which 1s 14 times

more potent than ipecac syrup. Side effects from the administration of ipecac syrup were minimal

in this study. All subjects felt drowsy after completing each separate phase of the study. Six of

the 17 subjects (351) reported having mild to moderate diarrhea. The diarrhea usually occurred

within two hours after taking the Ipecac syrup and usually resolved within six hours. No other

side effects were noted. No subject reported vomiting after leaving the health care facility.

CONCLUSION

This study establishes a relationship between volume of fluids taken with ipecac syrup and

the volume of the resulting emesis. When a 16 ounce volume of water was administered after the

ipecac syrup, a statistically greater volume of emesis was returned than when an 8 ounce volume

of water was administered. Although not statistically significant in this study, there was a trend

toward a shorter time to onset of vomiting, fewer number of single vomiting episodes, and more

volume per vomiting episode when 16 ounces of water was administered. Such a trend was not seen when compering the duration of vomiting between the two different volumes of fluid administered Therefore, a more efficient emetic reponse was produced when 16 ounces of water was administered.

The significance of this study as it relates to the emergency treatment of ingested poisons rests on the assumption that a greater volume of emesis returns a greater amount of the poison( s) ingested by the patient. If this assumption is valid, then these data suggest that larger amounts of

Ingested poisons can be removed from a patient by administration of larger volumes of fluid with ipecac syrup. Future studies might administer a non-toxic dose of a drug to test subjects. Some time later these subjects would be administered ipecac syrup along with differing amounts of fluids. After the induced emesis, blood levels of the previously administered drug would be measured. Such a stud/ would help determine If a relationship does exist between the volume of induced emesis and the effective removal of ingested poisons.

The results from this study suggest that a more efficient emesis is produced when 16 ounces of water is given with 1 ounce of ipecac syrup, and I would, therefore, recommend that larger volumes of fluid be administered when optimal emesis is needed. TABLES 11

Table 1. Subject characteristics

Subject Age Sex Weight (yrs) (lbs)

1 30 F 140

2 31 F 120

3 22 M 212

4 18 M 165

5 24 F 176

6 18 F 175

7 26 M 172

8 20 M 175

9 35 F 125

10 23 M 172

11 19 F 105

12 20 F 138

13 45 F 125

14 20 F 115

15 21 F 120

16 24 F 130

17 25 M 165

Mean ± SEN 25 ± 1.7 149 ±7.16 12

Table 2. Time to onset, number of single and major vomiting episodes, duration, and volume of ipecac-induced emesis with differing amounts of water

Subject 6roup Time to onset No. of single No. of major Duration Volume * (min) episodes episodes (min) (ml)

8oz. 16oz. 8oz. 16oz. 8oz. 16oz. 8oz, 16oz, 8oz. 16oz.

1 1 22 20 37 28 06 04 94 26 445 510

2 2 23 06 16 20 03 03 22 44 315 550

3 2 21 17 12 17 02 03 14 50 298 540

4 1 12 14 36 27 10 07 5B 72 435 485

5 1 10 07 28 18 10 06 45 24 390 630

6 1 11 18 18 20 08 06 51 58 358 545

7 1 13 10 29 24 07 05 66 66 345 570

8 2 19 11 17 29 03 05 38 61 360 545

9 1 08 08 29 23 04 04 61 66 360 690

10 1 13 23 12 10 03 02 11 11 360 600

11 2 11 08 15 10 04 06 36 33 337 653

12 2 46 29 07 08 Of 02 02 63 360 540

13 2 20 11 13 21 03 05 47 69 400 480

14 2 24 12 04 07 01 02 01 16 180 510

15 1 15 17 56 09 17 03 97 27 270 450

16 2 36 19 11 19 02 02 12 25 305 510

17 2 22 16 25 29 04 08 41 59 423 510

Mean 19 15 22 19 5.0 4,0 41 45 350 548

SEM 2.4 1.5 3,2 1.8 1.0 0,46 7,0 5.0 15.8 15.5 Table 3. Time between vomiting episodes, ml/single episode, and ml/major episode of ipecac-induced emesis with differing amounts of water

802. 16oz. (Mean ± SEM) (Mean ± SEM)

ml/ single episode 22 ± 2.9 37 ± 4.6 ml/major episode 110 ± 19.2 149* 17.0

Time between vomiting episodes 9.7 ± 1.1 10 ±1.6 (min) 14

Table 4, Comparison between the first and second phases In 0roup 1 and the first and second phases in Group 2

Group 1 Group 2

1st phase 2nd phase 1st phase 2nd phase

time to onset, min 13 ±1.5 15 ±2.1 14 ± 2.3 25 ± 3.4 (mean ± SEM)

* of single episodes 31 ±4.7 20 ±2.5 18 ±2.7 13 ±2.0 (mean ± SEM)

* of major episodes 8.1 ±1.6 4.6 ±.60 4.0 ±.71 2.6 ±.38 (mean ± SEM) duration, min 60 ±9.7 44 ± 8.5 47 ±6.2 24 ±5.8 (mean ± SEM) volume, ml 370 ±19.2 560 ±28.0 538 ±16.3 331 ±23.5 (mean ± SEM) Table 5. Comparison between subjects given 8 ounces of water first and subjects given 8 ounces of water second

8 oz 1st 8 02 2nd

no. of subjects sex 3li 3li 5F 6F weight, lbs 156 ±8.05 143± 11.5 (mean ± SEM) age.yrs 24 ±2.1 25 ±2.8 (mean ± SEM) time to onset, min 13 ±1.5 25 ±3.4 (mean ± SEM)

* of single episodes 31 ± 4.7 13 ± 2.0 (mean ± SEM)

* of major episodes 8.1 ±1.6 2.6 ±.38 (mean ± SEM) duration, min 60 ± 9.7 24 ± 5.8 (mean ± SEM) volume, ml 370 ± 19.2 331 ± 23.5 (mean ± SEM) Table 6, Comparison between subjects given 16 ounces of water first and subjects given 16 ounces of water second

16 oz 1st 16 oz 2nd

no, of subjects sex 3f1 3M 6F SF weight, lbs 143 ±11.5 156 ±8,05 (mean ± SEM) age.yrs 25 ±2.8 24 ±2.1 (mean ± SEM) time to onset, min 14 ±2.3 15 ±2.1 (mean ± SEM)

* of single episodes 18 ± 2.7 20 ± 2.5 (mean ± SEM)

* of major episodes 4.0 ± .11 4.6 ± .60 (meant SEM) duration, min 47 ± 6,2 44 ± 8,5 (mean ± SEM) volume, ml 538 ± 16.3 560 ± 28.0 (mean ± SEM) FIGURES 18

700 t

600

300

200 ••

1 00 J—H 1 1 1 1 1 1 1 1——I 1 1 1 i i 1 1 f 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Subject

Figure 1, Volume (ml) of ipecac-induced emesis with differing amounts of vater 19

50 t 45..

40-

35-

30- Minutes

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1? Subject Figure 2. Time to onset (min) of ipecac-Induced emesis with differing amounts of water 20

40 + Number of Episodes 30

I 2 3 4 5 6 7 8 9 10 III2 13 14 15 16 17 Subject Figure 3. Number of single vomiting episodes of ipecac-induced emesis with differing amounts of water 21

Number j q .. of Episodes 8 • • 6

4 2

0 1 2 3 4 5 6 7 S 9 10 1 1 12 13 14 15 16 17 Subject

Figure 4, Number of major vomiting episodes of ipecac-induced emesis with differing amounts of water IP

Minutes

I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Sdbjacl Figure 5, Duration of vomiting (min) of ipecac-induced emesis with differing amounts of water !

APPENDIX 1 pap 1 of 2

PARTICIPANT CONSENT FORM

You are Invited to participate in a pharmaceutical research project Involving ipecac syrup, a stomach irritant which induces vomiting. The purpose of this research is to determine if a relationship exists between volume of fluids taken with ipecac syrup and volume vomited.

As a participant, you will be Induced to vomit on two separate occasions. For each occasion, you will have taken nothing by mouth, solid or liquid, in the past eight hours. You will be given differing amounts of water to drink with the Ipecac syrup. The amount you vomit will be collected for measurement.

The duration of each occasion is dependent on the length of time the ipecac syrup requires to induce vomiting (usually 20 minutes) and the amount of time spent vomiting (may continue for up to 2 tours).

Harmful side effects from the use of ipecac syrup may involve the heart, nerve and muscle systems, the stomach and intestinal tract, prolonged vomiting, and aspiration of vomitus. However, these effects are extremely rare when ipecac syrup is properly administered. I pecac syrup has maintained a remarkable record of safety.

In the event you sustain physical injury resulting from the research project in which you are participating, the University of Utah will provide you, without charge, emergency and temporary medical treatment not otherwise covered try insurance. Furthermore, if your injuries are caused by negligent acts or (missions of University employees acting in the course and scope of their employment, the University may be liable, subject to limitations prescribed by law, for additional medical costs and other damages you sustain. If you believe that you have suffered a physical injury as a result of participation in this research program, please contact the Office of Research Administration, phone number 581 -6903.

For completing both phases of the study you will receive $ 100.00. The compensation is offered for your inconvenience. Your participation is voluntary, and you may withdraw from the study at any time, Approximately 20 participants will be Involved in this study.

Confidentiality of records which identify you by name will be maintained, although the Food and Drug Administration may inspect the records.

Please contact Ellen Jarvls for answers to any questions you may have about this research. The telephone number is 583-9256. 25

page 2 of 2

PARTICIPANT CONSENT FORM

By signing below you affirm that you have read and fully understand your participation in, and the nature of, this research.

Participant's Name (please print) Date

Signature of participant APPENDIX 2 PARTICIPANT DATA FORM

Participant * — Telephone * -

Age — Sex (M or F) -- Weight — __

Consent Form — Physical Exam

NPO 8 hours? —

8 oz. 16 oz.

Date

B.P, / Pulse

Onset (min.)

* Episodes

Length (min.)

Volume (ml) /

Mean Volume (ml)

Follow-up (Date & Time)

Date taken by: REFERENCES

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4. Corby D0, Decker WJ, Moran MJ, Payne CE. Clinical comparison of pharmacologic emeti in children. Pediatrics 1968;42:361-364.

5. Manoguerra AS, Krenzelok EP. Rapid emesis from high-dose ipecac syrup in adults and children intoxicated with antiemetics or other drugs. Am J Hosp Pharm 1978;35:1360-1362.

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13. GreenbergerNJ.IsselbacherKJ. Disorders of absorption. In Thorn GW, Adams RD, BraunwaldE, Isselbacher KJ, Petersdorf RG (eds). Harrison's Principles of Interna! Medicine. New York:McGraw Hill, 1977:1518-1537.

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17. MacLeod J. Ipecac intoxication-use of a cardiac pacemaker in management N Engl J Med 1963:268:146-147.

18. Dershewltz RA, Niederman LG, Ipecac at home-a health hazard? Clin Toxicol 1981;18:969-972.

19. Adler AG, Walinsky P, Krall RA, Cho SY. Death resulting from Ipecac syrup poisoning. JAMA 1980:243:1927.

20. Friedman EJ. Death from ipecac intoxication in a patient with anorexia nervosa. Am J Psychiatry 1984;141:702-703.

21. Brotman MC, Forbath N, Garfinkel PE, Humphrey JG. Myopathy due to ipecac syrup poisoning in a patient with anorexia nervosa. Can Med Assoc J 1981;125:453-454.

22. Tandberg D, Liechty EJ, Fishbein D. Mallory-Weiss syndrome: an unusual complication of ipecac-induced emesis. Ann Emerg Med 1981 ;10:521 -523. CURRICULUM VITAE

PERSONAL; Ellen Fassmann Jarvis Born April 15,1956, Salt Lake City, Utah

EDUCATION: Highland High School, Salt Lake City, Utah Graduated 1974

University of Utah, Salt Lake City, Utah Graduated 1979, Bachelor of Science - Pharmacy

University of Utah, Salt Lake City, Utah Graduated 1985, Doctor of Pharmacy

University of Utah, Salt Lake City, Utah 1983-1985 Clinical Pharmacy Residency

HONORS: Freshman Honor Society (Phi Sigma) Senior Honor Society (Phi Kappa Phi) Pharmacy Honor Society (Rho Chi) Dean's List Graduated Cum Laude Grace P. Swinyard Scholarship

EXPERIENCE: Third Avenue Pharmacy, Salt Lake City, Utah Pharmacist, 1979-1981

K-Mart Pharmacy, Salt Lake City, Utah Assistant Pharmacy Manager, 1981 -1982

K-Mart Pharmacy, Woodscross, Utah Pharmacy Manager, 1982-1983

University of Utah Hospital, Salt Lake City, Utah Clinical Pharmacy Resident, 1983-1985

PROFESSIONAL American Pharmaceutical Association SOCIETIES: Utah Pharmaceutical Association Utah Society of Hospital Pharmacists