- Email: [email protected]
Nitroglycerine ointment as aid to venous cannulation in children
Volume 111 Number 1
heterozygous expression in the family of our patient. Fanconi anemia, although associated with skeletal anomalies and hypoplastic marrow, is unlikely because no other hematologic abnormality has occurred over the 5-year follow up and there are no chromosomal aberrations. Folic acid deficiency, secondary to ingestion of goat milk during pregnancy, could be an additive contributor to this child's syndrome; even mild deficiency states produce a wide variety of severe malformations, but the majority are related to central nervous system defects, l~ The mother, however, was not known to have been anemic during or after the pregnancy. In our patient, the toxic effect was highly selective in affecting the committed red cell precursor series without alteration of the pluripotential stem cell. The severe decrease or absence of erythroid burst-forming suggests that a clone of cells was selectively destroyed sometime between the fourth and sixth weeks of development, when normal hematopoiesis ensues and is converting from yolk sac production to liver cell origin. The timing of the toxic insult during gestation can be clearly defined because forelimb bud development appears at the end of the fourth week of gestation, with identifiable structures developing by the sixth week. Hind limb development occurs somewhat later. Thus we can pinpoint the teratogenic effect to between the fifth and sixth weeks of embryonic development to account for this youngster's skeletal and vascular abnormalities and red cell aplasia. H
Clinical and laboratory observations
89
This case provides circumstantial evidence for the transmission of a toxic material through goat milk, presumed to be anagyrine, resulting in bilateral radial hemimelia and pure red cell aplasia. REFERENCES 1. Wagon KA. Lupine poisoning as a possible factor in congenital deformities in cattle. J Range Mgmt 1960;13:89-91. 2. Binns W, James LF, Beeson KC, Holley RA. A congenital deformity experimentally produced by feeding lupine and lead. Proc Am Col Vet Toxicol 1961;29-32. 3. Shupe JL, Binns W, James LF, Keeler RF. Lupine, a cause of crooked calf disease. J Am Vet Med Assoc 1966;151:198203. 4. Kilgore WW, Crosby DG, Craigrnill AL, Poppen NK. Toxic plants as possible human teratogens. Calif Agr 1981;35:6. 5. Meytes D, Ma A, Ortega JA, Shore NA, Dukes PP. Human erythroid burst-promoting activity produced by phytohemagglutinin-stimulated, radioresistant peripheral blood mononuclear cells. Blood 1979;54:1050-7. 6. Shupe JL, Lyn F J, Binns W. Observations on crooked calf disease. J Am Vet Med Assoc 1967;151:191-4. 7. Keeler RF. Lupine alkaloids from teratogenic and nonteratogenic lupines. Teratology 1973;7:23-30. 8. Alter BP, Nathan DG. Red cell aplasia in children. Arch Dis Child 1979;54:263-7. 9. Aase JM, Smith DW. Congenital anemia and triphalangeal thumbs: a new syndrome. J PEmATR 1969;74:471-4. 10. Hurley LS. Developmental nutrition. Engtewood Cliffs, N.J.: Prentice-Hall, 1980;154-160. 11. Pansky B. Medical embryology. New York: Macmillan, 1982:58-61, 184-5, 292-5.
Nitroglycerine o i n t m e n t as aid to venous c a n n u l a t i o n in children G. Vaksmann, M.D., C. Rey, M.D., G.-M. Breviere, M.D., D. Smadja, M.D., and C. Dupuis, M.D. From the Department of Pediatric Cardiology, UniversityHospital, Lille, France
Intravenous insertion of needles requires particular skill in children because they have smaller and more reactive veins than do adults and venous cannulation is often difficult or even impossible. Hecker et al. ~ have reported the use of nitroglycerine ointment as an aid to venipuncture in adults. Thus we decided to study the effects of nitroglycerine ointment on veins and ease of venous cannulation in children.
Submitted for publication June 10, 1986; accepted Feb. 3, 1987. Reprint requests: Guy Vaksmann, M.D., Department of Pediatric Cardiology, University Hospital, 59037 Lille C6dex, France.
METHODS The study group consisted of 150 patients referred to our pediatric department and in whom infusion was needed. These children were divided into three groups of 50 patients. In group 1, nitroglycerine ointment was applied to the skin of the wrist or the forearm before venipuncture; in group 2, a bland ointment was applied to the venipuncture site; and in group 3, nitroglycerine ointment was applied elsewhere on the body, in an area not to be punctured. The device used for cannulation was a 22- or 24-gauge needle. Ointment application and venous cannulation took place in a room at mean temperature 23 ~ C. Ointments were applied in all groups 10 to 15 minutes
9O
Clinical and laboratory observations
The Journal of Pediatrics July 1987
GROUP I GROUP 2
5"
CANNULATION SCORE
J'-"-I GROUP 3 4
1
AGE NUMBER
(MONTHS)
OF P A T I E N T S
o-1 11/11/12
i 1-12
12-eo
>60
17/11/15
13/18/13
9/10/10
Figure. Relation of age to ease of cannulation. Difficulty in cannulation was assessed on scale of 1 (very easy) to 5 (failure). Diagram shows mean (_+SD) score of cannulation in patients with local application of nitroglycerine ointment (group 1), with local application of bland ointment (group 2), or with application of nitroglycerine in area remote from that to be punctured (group 3). *Significant (P <0.05) difference for group 1 vs group 2 or 3.
before puncture. The cannulas were inserted by one of four nurses, who did not know which substance was applied or where. Each nurse did punctures in nearly the same number of patients from each of the three groups. In groups 1 and 3, 0. I to 0.2 m L 0.4% nitroglycerine ointment was rubbed into the skin, 0.4 mg nitroglycerine in patients younger than 1 year and 0.8 mg in the older children. In addition, to evaluate possible systemic effects of nitroglycerine, eight children were studied during cardiac catheterization. Six had atrial septal defect, and two had complete atrioventricular canal. H e a r t rate, right and left ventricular pressures, and pulmonary artery pressure were measured before and 30 minutes after application of nitroglycerine ointment (0.1 m L / 5 kg body weight). Statistical analysis was performed by means of the Student t test or chi-square analysis. RESULTS The degree of difficulty in cannulation was assessed on a scale of 1 (very easy) to 5 (failure) by the nurse who carried out the puncture. The mean score for group 1 (2.24 ___ 1.32) was significantly lower than that for group 2 (3.02 + 1.62, t = 2.6, P = 0.01) or group 3 (2.86 _+ 1.36, t = 2.3, P = 0.02). The mean score for group 2 was not significantly different from that for group 3. It appeared that benefit from local application of nitroglycerine was greater in children younger than 1 year (Figure). Indeed, no significant benefit was apparent in patients older than 1 year. At the time of venous cannulation, the patient's veins in the area to be punctured were assessed as palpable, dilated,
visible, or not visible. Chi-square analysis showed no significant difference among the three groups at any age. In 10 patients from group 2 with failure of venous cannulation, a second attempt was made in the same place and by the same nurse after application of nitroglycerine ointment. In six patients, this second effort led to a successful cannulation. These six were not included in the treated group. No significant modification of hemodynamic status was observed 30 minutes after application of nitroglycerine ointment in the eight patients who had cardiac catheterization. DISCUSSION Nitroglycerine 2% ointment is widely used in adults for treatment of angina 2 and heart failure? We have used a concentration of 0.4% of this drug in infants and children with coarctation of the aorta or cardiomyopathy, because of its systemic venous and arterial vasodilator effects. The final dose was probably about 2 m g / k g / d . For venous cannulation, we restricted the amount applied to 0.4 or 0.8 mg nitroglycerine, to minimize the risks of systemic effects while providing a high local concentration. Indeed, no side effects, such as headache or postural dizziness, were reported by older children, and we observed no change in hemodynamic status 30 minutes after application of nitroglycerine in the eight patients who had cardiac catheterization. Nitroglycerine ointment is fully effective as soon as 30 minutes after application, + so we conclude that this amount of nitroglycerine ointment has no systemic effect.
Volume 111 Number 1 In our study, the beneficial effects of locally applied nitroglycerine on the ease of cannulation were confined to children younger than 1 year, whereas no significant benefit was found in older children. On the other hand, no significant difference in venous status was apparent, even in younger patients. The lack of efficacy of nitroglYcerine in group 3 patients indicates local action of this drug rather than systemic effect. Greater ease of cannulation may result from diminished venous reactivity to puncture, induced b y t h e local antispastic vascular action of nitroglycerine. Nitroglycerine may be more effective in younger children, because they have smaller and more reactive veins than do older patients. These results may also be related to a larger dose per unit of body weight or to thinner skin with more rapid absorption in th e younger patient s . In any case, the Usual ease of venous cannulation in older Children reduces the need for nitroglycerine.
Clinical and laboratory observations
91
We conclude that local application of nitroglycerine ointment is an efficient way of reducing failure in venous cannulation in infants; this technique appears to be simple and innocuous. We thank Francois Leung for help in preparation of the manuscript.
REFERENCES 1. Hecker JF, Lewis GBH, Stanley H. Nitroglycerine ointment as anaid to venepuncture. Lancet 1983;1:332. 2. Reichek N, Goldstein RE, Redmond DR, Epstein SE. Sustained' effects o f nitroglycerin ointment in patients with angina pectoris. Circulation 1974;50:348. 3. Taylor WR, Forrester JS, Magnusson P, Takano T, Chatterjee K, Swan HJC. Hemodynamic effects of nitroglycerin ointment in congestive heart failure. Am J Cardiol 1976; 38:469. 4. Armstrong PW, Armstrong JA, Marks GS. Pharmacokinetichemodynamic studies of nitroglycerin ointment in Congestive heart failure. Am J Cardiol 1980;46:670.
Efficacy of lactase-treated milk for lactose-intolerant pediatric patients Jeffrey A. Biller, M.D., Sheila King, B,S., A n d r e a Rosenthal, B.S,, a n d Richard J. Grand, M.DI From the Division of Pediatric Gastroenterology and Nutrition, Boston Floating Hospital, New England Medical Center, and the Department of Pediatrics, Tufts University School of Medicine, Boston
Lactose malabsorption is a common problem in childhood, and may be associated with eructation or flatus, diarrhea. bloating, and abdominal pain. 1,2 In young children it is often transient, usually following an infectious enteritis; less commonly it is associated with bacterial overgrowth or a primary mucosal abnormality such as celiac disease. Familial absence of lactase is rare, and symptoms appear shortly after the introduction of milk2 In older children, lactose malabsorption may result from a genetic "late onset" deficiency of lactase, which has been recognized in the United States more frequently in black children after age 3 years and in white children after age 5 years, j Because milk constitutes a major source of carbohYdrate and calcium in the diet of children, restriction or eliminaSupported by Kremers Urban Company, Milwaukee. Submitted for publication Oct. 24. 1986: accepted Feb. 10. 1987. Reprint requests: Jeffrey A. Biller, M.D.. Division of Pediatric Gastroenterology and Nutrition, Boston Floating Hospital. New England Medical Center, Boston. MA 02111.
tion of lactose-containing foods poses a potential nutritional risk. The addition of various/3rgalactosidases obtained from fungi and yeasts to milk 4,5 has offered an alternative for patients with lactose intolerance. Until recently, such enzyme preparations required 12 to 24 hours incubation for effective hydrolys!s of lactose, thereby obviating much of their usefulness away from the home. Recently, Rosado et al. 6 documented in adults the efficacy of adding to milk just prior to ingestion the/3-galactosidases derived from the yeast Kluyverornyces lactis (LactAid, SugarLo Co., Pleasantville, N.J.~. They showed a decrease in both breath hydrogen production (as a manifestation of lactose malabsorption, defined as an increase in hydrogen concentration >20 ppm above baseline) and clinical symptoms after milk ingestion. We ~/ssessed the efficacy of a different/%galactosidase, derived from the fungus Aspergillus oryzae (Lactrase, Kremers Urban Company, Milwaukee) on in vivo hydrolysis Of lactose in milk in children with lactose intolerance.
heterozygous expression in the family of our patient. Fanconi anemia, although associated with skeletal anomalies and hypoplastic marrow, is unlikely because no other hematologic abnormality has occurred over the 5-year follow up and there are no chromosomal aberrations. Folic acid deficiency, secondary to ingestion of goat milk during pregnancy, could be an additive contributor to this child's syndrome; even mild deficiency states produce a wide variety of severe malformations, but the majority are related to central nervous system defects, l~ The mother, however, was not known to have been anemic during or after the pregnancy. In our patient, the toxic effect was highly selective in affecting the committed red cell precursor series without alteration of the pluripotential stem cell. The severe decrease or absence of erythroid burst-forming suggests that a clone of cells was selectively destroyed sometime between the fourth and sixth weeks of development, when normal hematopoiesis ensues and is converting from yolk sac production to liver cell origin. The timing of the toxic insult during gestation can be clearly defined because forelimb bud development appears at the end of the fourth week of gestation, with identifiable structures developing by the sixth week. Hind limb development occurs somewhat later. Thus we can pinpoint the teratogenic effect to between the fifth and sixth weeks of embryonic development to account for this youngster's skeletal and vascular abnormalities and red cell aplasia. H
Clinical and laboratory observations
89
This case provides circumstantial evidence for the transmission of a toxic material through goat milk, presumed to be anagyrine, resulting in bilateral radial hemimelia and pure red cell aplasia. REFERENCES 1. Wagon KA. Lupine poisoning as a possible factor in congenital deformities in cattle. J Range Mgmt 1960;13:89-91. 2. Binns W, James LF, Beeson KC, Holley RA. A congenital deformity experimentally produced by feeding lupine and lead. Proc Am Col Vet Toxicol 1961;29-32. 3. Shupe JL, Binns W, James LF, Keeler RF. Lupine, a cause of crooked calf disease. J Am Vet Med Assoc 1966;151:198203. 4. Kilgore WW, Crosby DG, Craigrnill AL, Poppen NK. Toxic plants as possible human teratogens. Calif Agr 1981;35:6. 5. Meytes D, Ma A, Ortega JA, Shore NA, Dukes PP. Human erythroid burst-promoting activity produced by phytohemagglutinin-stimulated, radioresistant peripheral blood mononuclear cells. Blood 1979;54:1050-7. 6. Shupe JL, Lyn F J, Binns W. Observations on crooked calf disease. J Am Vet Med Assoc 1967;151:191-4. 7. Keeler RF. Lupine alkaloids from teratogenic and nonteratogenic lupines. Teratology 1973;7:23-30. 8. Alter BP, Nathan DG. Red cell aplasia in children. Arch Dis Child 1979;54:263-7. 9. Aase JM, Smith DW. Congenital anemia and triphalangeal thumbs: a new syndrome. J PEmATR 1969;74:471-4. 10. Hurley LS. Developmental nutrition. Engtewood Cliffs, N.J.: Prentice-Hall, 1980;154-160. 11. Pansky B. Medical embryology. New York: Macmillan, 1982:58-61, 184-5, 292-5.
Nitroglycerine o i n t m e n t as aid to venous c a n n u l a t i o n in children G. Vaksmann, M.D., C. Rey, M.D., G.-M. Breviere, M.D., D. Smadja, M.D., and C. Dupuis, M.D. From the Department of Pediatric Cardiology, UniversityHospital, Lille, France
Intravenous insertion of needles requires particular skill in children because they have smaller and more reactive veins than do adults and venous cannulation is often difficult or even impossible. Hecker et al. ~ have reported the use of nitroglycerine ointment as an aid to venipuncture in adults. Thus we decided to study the effects of nitroglycerine ointment on veins and ease of venous cannulation in children.
Submitted for publication June 10, 1986; accepted Feb. 3, 1987. Reprint requests: Guy Vaksmann, M.D., Department of Pediatric Cardiology, University Hospital, 59037 Lille C6dex, France.
METHODS The study group consisted of 150 patients referred to our pediatric department and in whom infusion was needed. These children were divided into three groups of 50 patients. In group 1, nitroglycerine ointment was applied to the skin of the wrist or the forearm before venipuncture; in group 2, a bland ointment was applied to the venipuncture site; and in group 3, nitroglycerine ointment was applied elsewhere on the body, in an area not to be punctured. The device used for cannulation was a 22- or 24-gauge needle. Ointment application and venous cannulation took place in a room at mean temperature 23 ~ C. Ointments were applied in all groups 10 to 15 minutes
9O
Clinical and laboratory observations
The Journal of Pediatrics July 1987
GROUP I GROUP 2
5"
CANNULATION SCORE
J'-"-I GROUP 3 4
1
AGE NUMBER
(MONTHS)
OF P A T I E N T S
o-1 11/11/12
i 1-12
12-eo
>60
17/11/15
13/18/13
9/10/10
Figure. Relation of age to ease of cannulation. Difficulty in cannulation was assessed on scale of 1 (very easy) to 5 (failure). Diagram shows mean (_+SD) score of cannulation in patients with local application of nitroglycerine ointment (group 1), with local application of bland ointment (group 2), or with application of nitroglycerine in area remote from that to be punctured (group 3). *Significant (P <0.05) difference for group 1 vs group 2 or 3.
before puncture. The cannulas were inserted by one of four nurses, who did not know which substance was applied or where. Each nurse did punctures in nearly the same number of patients from each of the three groups. In groups 1 and 3, 0. I to 0.2 m L 0.4% nitroglycerine ointment was rubbed into the skin, 0.4 mg nitroglycerine in patients younger than 1 year and 0.8 mg in the older children. In addition, to evaluate possible systemic effects of nitroglycerine, eight children were studied during cardiac catheterization. Six had atrial septal defect, and two had complete atrioventricular canal. H e a r t rate, right and left ventricular pressures, and pulmonary artery pressure were measured before and 30 minutes after application of nitroglycerine ointment (0.1 m L / 5 kg body weight). Statistical analysis was performed by means of the Student t test or chi-square analysis. RESULTS The degree of difficulty in cannulation was assessed on a scale of 1 (very easy) to 5 (failure) by the nurse who carried out the puncture. The mean score for group 1 (2.24 ___ 1.32) was significantly lower than that for group 2 (3.02 + 1.62, t = 2.6, P = 0.01) or group 3 (2.86 _+ 1.36, t = 2.3, P = 0.02). The mean score for group 2 was not significantly different from that for group 3. It appeared that benefit from local application of nitroglycerine was greater in children younger than 1 year (Figure). Indeed, no significant benefit was apparent in patients older than 1 year. At the time of venous cannulation, the patient's veins in the area to be punctured were assessed as palpable, dilated,
visible, or not visible. Chi-square analysis showed no significant difference among the three groups at any age. In 10 patients from group 2 with failure of venous cannulation, a second attempt was made in the same place and by the same nurse after application of nitroglycerine ointment. In six patients, this second effort led to a successful cannulation. These six were not included in the treated group. No significant modification of hemodynamic status was observed 30 minutes after application of nitroglycerine ointment in the eight patients who had cardiac catheterization. DISCUSSION Nitroglycerine 2% ointment is widely used in adults for treatment of angina 2 and heart failure? We have used a concentration of 0.4% of this drug in infants and children with coarctation of the aorta or cardiomyopathy, because of its systemic venous and arterial vasodilator effects. The final dose was probably about 2 m g / k g / d . For venous cannulation, we restricted the amount applied to 0.4 or 0.8 mg nitroglycerine, to minimize the risks of systemic effects while providing a high local concentration. Indeed, no side effects, such as headache or postural dizziness, were reported by older children, and we observed no change in hemodynamic status 30 minutes after application of nitroglycerine in the eight patients who had cardiac catheterization. Nitroglycerine ointment is fully effective as soon as 30 minutes after application, + so we conclude that this amount of nitroglycerine ointment has no systemic effect.
Volume 111 Number 1 In our study, the beneficial effects of locally applied nitroglycerine on the ease of cannulation were confined to children younger than 1 year, whereas no significant benefit was found in older children. On the other hand, no significant difference in venous status was apparent, even in younger patients. The lack of efficacy of nitroglYcerine in group 3 patients indicates local action of this drug rather than systemic effect. Greater ease of cannulation may result from diminished venous reactivity to puncture, induced b y t h e local antispastic vascular action of nitroglycerine. Nitroglycerine may be more effective in younger children, because they have smaller and more reactive veins than do older patients. These results may also be related to a larger dose per unit of body weight or to thinner skin with more rapid absorption in th e younger patient s . In any case, the Usual ease of venous cannulation in older Children reduces the need for nitroglycerine.
Clinical and laboratory observations
91
We conclude that local application of nitroglycerine ointment is an efficient way of reducing failure in venous cannulation in infants; this technique appears to be simple and innocuous. We thank Francois Leung for help in preparation of the manuscript.
REFERENCES 1. Hecker JF, Lewis GBH, Stanley H. Nitroglycerine ointment as anaid to venepuncture. Lancet 1983;1:332. 2. Reichek N, Goldstein RE, Redmond DR, Epstein SE. Sustained' effects o f nitroglycerin ointment in patients with angina pectoris. Circulation 1974;50:348. 3. Taylor WR, Forrester JS, Magnusson P, Takano T, Chatterjee K, Swan HJC. Hemodynamic effects of nitroglycerin ointment in congestive heart failure. Am J Cardiol 1976; 38:469. 4. Armstrong PW, Armstrong JA, Marks GS. Pharmacokinetichemodynamic studies of nitroglycerin ointment in Congestive heart failure. Am J Cardiol 1980;46:670.
Efficacy of lactase-treated milk for lactose-intolerant pediatric patients Jeffrey A. Biller, M.D., Sheila King, B,S., A n d r e a Rosenthal, B.S,, a n d Richard J. Grand, M.DI From the Division of Pediatric Gastroenterology and Nutrition, Boston Floating Hospital, New England Medical Center, and the Department of Pediatrics, Tufts University School of Medicine, Boston
Lactose malabsorption is a common problem in childhood, and may be associated with eructation or flatus, diarrhea. bloating, and abdominal pain. 1,2 In young children it is often transient, usually following an infectious enteritis; less commonly it is associated with bacterial overgrowth or a primary mucosal abnormality such as celiac disease. Familial absence of lactase is rare, and symptoms appear shortly after the introduction of milk2 In older children, lactose malabsorption may result from a genetic "late onset" deficiency of lactase, which has been recognized in the United States more frequently in black children after age 3 years and in white children after age 5 years, j Because milk constitutes a major source of carbohYdrate and calcium in the diet of children, restriction or eliminaSupported by Kremers Urban Company, Milwaukee. Submitted for publication Oct. 24. 1986: accepted Feb. 10. 1987. Reprint requests: Jeffrey A. Biller, M.D.. Division of Pediatric Gastroenterology and Nutrition, Boston Floating Hospital. New England Medical Center, Boston. MA 02111.
tion of lactose-containing foods poses a potential nutritional risk. The addition of various/3rgalactosidases obtained from fungi and yeasts to milk 4,5 has offered an alternative for patients with lactose intolerance. Until recently, such enzyme preparations required 12 to 24 hours incubation for effective hydrolys!s of lactose, thereby obviating much of their usefulness away from the home. Recently, Rosado et al. 6 documented in adults the efficacy of adding to milk just prior to ingestion the/3-galactosidases derived from the yeast Kluyverornyces lactis (LactAid, SugarLo Co., Pleasantville, N.J.~. They showed a decrease in both breath hydrogen production (as a manifestation of lactose malabsorption, defined as an increase in hydrogen concentration >20 ppm above baseline) and clinical symptoms after milk ingestion. We ~/ssessed the efficacy of a different/%galactosidase, derived from the fungus Aspergillus oryzae (Lactrase, Kremers Urban Company, Milwaukee) on in vivo hydrolysis Of lactose in milk in children with lactose intolerance.