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Effect of Milk on Ipecac-Induced Emesis
Effect of Milk on Ipecac-Induced Emesis Robert J. Varipapa and Gary M. Oderda The effect of milk on the onset of emesis produced by ipecac was determined. Using a crossover design, it was found that milk
significantly increased the time to onset of emesis produced by ipecac syrup. The authors conclude that ipecac should not be
administered with milk and recommend that ipecac syrup be administered with water when possible.
Ipecac syrup is presently the emetic of choice in drug overdoses and poison ingestions. To produce emesis, 15 ml of the syrup is administered with 240 ml of liquid. If emesis does not occur in 15 to 20 minutes, the regimen should be repeated. 1 In a number of instances, we noted that milk appeared to delay the onset of emesis produced by ipecac. To determine if these observations were clinically important, the following study was performed. Preliminary data were published earlier;2 we now present the report in its entirety. Eleven healthy adult volunteers, who were told of the procedures involved and who were paid to participate in the study, signed consent forms approved by the Human Volunteers Research Committee. The subjects were divided randomly into two groups. Those in the first group were given 15 ml of ipecac syrup immediately followed by eight ounces of milk in the first trial, and by eight ounces of water in the second trial. The two trials were separated by at least one week. The order of administration of milk and water was reversed for the second group. If emesis did not occur within 30 minutes, the regimen was repeated. The time from ipecac administration to emesis was determined. Blood pressure, pulse rate and respiratory rate were noted before administration of ipecac and immediately after emesis. All subjects had fasted for at least four hours prior to administration of ipecac and remained seated throughout the entire procedure.
Figure 1. Time to emesis with ipecac administered with water and milk (nine subjects). Time to 70 emesis (minutes) 60
at the chemoreceptor trigger zone. Decreased absorption may be produced by changes in gastric pH or by the complexation of ipecac with milk's protein and lipid constituents. Although the major site of absorption of ipecac is unknown, if it is absorbed in the duodenum, inhibition of gastric emptying time by milk4 would be expected to delay ipecac's absorption, and consequentially, emesis. Since, in most cases, increases in pulse rate, blood pressure and respiratory rate were noted following ipecac-induced emesis, this procedure must be used with caution in patients with compromised cardiac function. One subject with a history of fainting fainted 15 minutes after administration of ipecac with milk. His blood pressure fell to 100/60 mm Hg from a baseline level of 115/70 mm Hg. We attributed this fall to a vasovagal reaction. This subject did not receive a second dose of ipecac and was dropped from the study. The most frequent adverse reaction, reported in 60 percent of the group, was transient diarrhea occurring one to three hours after administration of ipecac.
Results
The average time (± standard error) to induction of emesis with water was 23.9 ± 3.25 minutes. When milk was given, the average time increased to 34.5 ± 3.97 minutes. The difference in induction time was signifiRobert J. Varlpapa, PharmD, is Assistant Editor, American Hospital Formulary Service, American Society of Hospital Pharmacists, Washington, D.C. 20014. Gary M. Oderda, PharmD, is Director of the Maryland Poison Information Center, School of Pharmacy, University of Maryland at Baltimore, Baltimore, Maryland 21201 . The authors are indebted to Mary S. Furth, MD, MPH; J. Edward Moreton, PhD; Jacquelyn S. Lucy, MEd; and Frank Palumbo, PhD, for their advice on this article, and to Annette Syers for her secretarial skills.
50 40
30 20
.
~'
10
Water
Milk Group 0.05) using the paired two-tail
cant (P < t-test. Only one of the nine subjects included in the statistical analysis vomited in a shorter period of time when milk was administered (Figure 1, above). Two other subjects were dropped from the study and are not included in the analysis. One, who seemed resistant to the effects of ipecac, vomited four and a half hours after administration with water and not at all after milk. The other fainted 15 minutes after administration of ipecac and milk. The following average changes (and range) of vital signs were noted from induction of emesis by ipecac: systolic blood pressure +14.3 (0-35) mm Hg, diastolic blood pressure +8.7 (0-20) mm Hg, pulse · rate +24 (15-56) per minute, respiratory rate +4.4 (0-8) per minute. The data indicate an apparent interaction between milk and ipecac syrup which results in a significant delay of emesis. It appears that the combination of water and ipecac is preferred. The exact mechanism of this interaction is unknown. Milk, by acting as a demulcent, 3 may inhibit the gastric irritation produced by ipecac. It also may retard the absorption of ipecac, thereby diminishing its central action 510
Conclusion
The data indicate that ipecac syrup should not be administered with milk. Since no studies indicate otherwise, we recommend that ipecac syrup be administered with water when possible. Practitioners should be aware that ingestion of milk following an acute intoxication may delay emesis produced by subsequent administration of ipecac. Further study is needed to delineate the advantages and disadvantages of methods of administration and dosing of ipecac syrup. • References 1. Oderda, G.M., and West, S.: Emetic and antiemetic products, in Handbook of nonprescription drugs, fifth edition, American Pharmaceutical Association, Washington, D.C., 1977, p. 57. 2. Varipapa, R.J ., and Oderda, G.M.: Effect of milk on ipecac-induced emesis, N. Engl. J. Med. 296: 112-113, (Jan. 13) 1977. 3. Arena, J.M. : Poisoning, third edition, Charles C Thomas, Springfield, Illinois, 1974. 4. Mos'panov, L.S.: The effect of some dairy products on gastric motor function, Vopr. Pitan 25: 76-79, 1966. This study was supported in part by a student research grant from the American Association of Poison Control Centers.
Journal of the American Pharmaceutical Association
significantly increased the time to onset of emesis produced by ipecac syrup. The authors conclude that ipecac should not be
administered with milk and recommend that ipecac syrup be administered with water when possible.
Ipecac syrup is presently the emetic of choice in drug overdoses and poison ingestions. To produce emesis, 15 ml of the syrup is administered with 240 ml of liquid. If emesis does not occur in 15 to 20 minutes, the regimen should be repeated. 1 In a number of instances, we noted that milk appeared to delay the onset of emesis produced by ipecac. To determine if these observations were clinically important, the following study was performed. Preliminary data were published earlier;2 we now present the report in its entirety. Eleven healthy adult volunteers, who were told of the procedures involved and who were paid to participate in the study, signed consent forms approved by the Human Volunteers Research Committee. The subjects were divided randomly into two groups. Those in the first group were given 15 ml of ipecac syrup immediately followed by eight ounces of milk in the first trial, and by eight ounces of water in the second trial. The two trials were separated by at least one week. The order of administration of milk and water was reversed for the second group. If emesis did not occur within 30 minutes, the regimen was repeated. The time from ipecac administration to emesis was determined. Blood pressure, pulse rate and respiratory rate were noted before administration of ipecac and immediately after emesis. All subjects had fasted for at least four hours prior to administration of ipecac and remained seated throughout the entire procedure.
Figure 1. Time to emesis with ipecac administered with water and milk (nine subjects). Time to 70 emesis (minutes) 60
at the chemoreceptor trigger zone. Decreased absorption may be produced by changes in gastric pH or by the complexation of ipecac with milk's protein and lipid constituents. Although the major site of absorption of ipecac is unknown, if it is absorbed in the duodenum, inhibition of gastric emptying time by milk4 would be expected to delay ipecac's absorption, and consequentially, emesis. Since, in most cases, increases in pulse rate, blood pressure and respiratory rate were noted following ipecac-induced emesis, this procedure must be used with caution in patients with compromised cardiac function. One subject with a history of fainting fainted 15 minutes after administration of ipecac with milk. His blood pressure fell to 100/60 mm Hg from a baseline level of 115/70 mm Hg. We attributed this fall to a vasovagal reaction. This subject did not receive a second dose of ipecac and was dropped from the study. The most frequent adverse reaction, reported in 60 percent of the group, was transient diarrhea occurring one to three hours after administration of ipecac.
Results
The average time (± standard error) to induction of emesis with water was 23.9 ± 3.25 minutes. When milk was given, the average time increased to 34.5 ± 3.97 minutes. The difference in induction time was signifiRobert J. Varlpapa, PharmD, is Assistant Editor, American Hospital Formulary Service, American Society of Hospital Pharmacists, Washington, D.C. 20014. Gary M. Oderda, PharmD, is Director of the Maryland Poison Information Center, School of Pharmacy, University of Maryland at Baltimore, Baltimore, Maryland 21201 . The authors are indebted to Mary S. Furth, MD, MPH; J. Edward Moreton, PhD; Jacquelyn S. Lucy, MEd; and Frank Palumbo, PhD, for their advice on this article, and to Annette Syers for her secretarial skills.
50 40
30 20
.
~'
10
Water
Milk Group 0.05) using the paired two-tail
cant (P < t-test. Only one of the nine subjects included in the statistical analysis vomited in a shorter period of time when milk was administered (Figure 1, above). Two other subjects were dropped from the study and are not included in the analysis. One, who seemed resistant to the effects of ipecac, vomited four and a half hours after administration with water and not at all after milk. The other fainted 15 minutes after administration of ipecac and milk. The following average changes (and range) of vital signs were noted from induction of emesis by ipecac: systolic blood pressure +14.3 (0-35) mm Hg, diastolic blood pressure +8.7 (0-20) mm Hg, pulse · rate +24 (15-56) per minute, respiratory rate +4.4 (0-8) per minute. The data indicate an apparent interaction between milk and ipecac syrup which results in a significant delay of emesis. It appears that the combination of water and ipecac is preferred. The exact mechanism of this interaction is unknown. Milk, by acting as a demulcent, 3 may inhibit the gastric irritation produced by ipecac. It also may retard the absorption of ipecac, thereby diminishing its central action 510
Conclusion
The data indicate that ipecac syrup should not be administered with milk. Since no studies indicate otherwise, we recommend that ipecac syrup be administered with water when possible. Practitioners should be aware that ingestion of milk following an acute intoxication may delay emesis produced by subsequent administration of ipecac. Further study is needed to delineate the advantages and disadvantages of methods of administration and dosing of ipecac syrup. • References 1. Oderda, G.M., and West, S.: Emetic and antiemetic products, in Handbook of nonprescription drugs, fifth edition, American Pharmaceutical Association, Washington, D.C., 1977, p. 57. 2. Varipapa, R.J ., and Oderda, G.M.: Effect of milk on ipecac-induced emesis, N. Engl. J. Med. 296: 112-113, (Jan. 13) 1977. 3. Arena, J.M. : Poisoning, third edition, Charles C Thomas, Springfield, Illinois, 1974. 4. Mos'panov, L.S.: The effect of some dairy products on gastric motor function, Vopr. Pitan 25: 76-79, 1966. This study was supported in part by a student research grant from the American Association of Poison Control Centers.
Journal of the American Pharmaceutical Association