- Email: [email protected]
Radionuclide angiography in evaluation of PDA
17 2
E d i t o r i a l cor'respondence
The Journal o f Pediatrics July 1983
are not sufficiently aware of the initial symptoms of West syndrome. Too often the myoclonic jerks are attributed to fright or colic. 5. As to the importance of early therapy, Sorel was certainly the first to stress this. It was our aim to emphasize that once there is established brain damage and mental retardation resulting from infantile spasms (or preceding them), hormonal or any other therapy cannot be expected to reverse these. Hence the vital importance of treating patients before retardation develops. 6. We have observed in six patients that high doses of tetracosactrin significantly improved the mental status of patients who had previously been treated inadequately and who showed continuing spasms and no change in the EEG while receiving prolonged conventional treatment. Indeed, with our new protocol, spasms cease and the hypsarrhythmia resolves after the second injection of 1 mg tetracosactrin depot in almost every case. Since completion of our paper, we have treated another four patients with such results. These results are in contrast to those obtained in the 1960s, when 40 units A C T H were administered. In many of the patients receiving this treatment, spasms continued for weeks and mental recovery was rare. The full version of our paper included the details of these cases. 7. As to the hazards of A C T H therapy, it would appear from Riikonen's work, as well as from our own experience, that conventional doses are as dangerous as high doses. One way to minimize infections is not to hospitalize these patients during evaluation and therapy.
P. Lerman, M.D. Head EEG Laboratory Beilinson Medical Center Petak-Tiqua, Israel
Bone infarction in sickle cell disease To the Editor: I read with interest the article by Keeley and Buchanan. ~ They have attempted to separate, clinically, acute bone marrow infarcts without cortical involvement from cortical infarction with or without marrow involvement. They also address the problem of distinguishing between sterile bone infarcts and those complicated by osteomyelitis. In a recent monograph on this subject) I noted that "One large deficiency in approaching the problem of distinguishing between aseptic and septic bone infarcts is the lack of any large series of proven cases of aseptic cortical osteonecrosis of long bones." Keeley and Buchanan have now made a start in this direction. The authors misread the figures 3 when they stated that 50% of the cases I reviewed had "three-segment lesions." Actually it was stated that three-segment lesions generally seem to account for about 50% of the cases in Ibadan, but in my s ~ d y they constituted 32%. A chart (Fig. 2) indicated that 52 of 198 lesions (26%) were three-segment lesions. There are many possible reasons for differences between the two groups of patients, considering that one group is in West Africa and one is in the United States. The former frequently have
other medical problems, such as anemia from other causes, parasites, malaria, and malnutrition. Additionally, as the West African patients were younger, the periosteum could more easily be separated from the cortex to reveal a more extensive bone process radiographically. Even within the West African group, younger patients were found to have more three-segment lesions.
Stanley P. Bohrer, M.D., M.P.H. Bowman Gray School o f Medicine 300 S. Hawthorne Rd. Winston-Salem, N C 27103 REFERENCES 1. 2. 3.
Keetey K, Buchanan: Acute infarction of long bones in children with sickle cell anemia. J PEt)IATR 101:170, 1982. Bohrer SP: Bone ischemia and infarction in sickle ce!l disease. St. Louis, 1981, Warren H. Green, p 134. Bohrer SP: Acute long bone diaphyseal infarcts in sickle cell disease. Br J Radiol 43:685, 1970.
Radionuclide angiography in evaluation of PDA To the Editor: W e wish to comment on the article of Vick et al., Lregarding the use of radionuclide angiography in the evaluation of shunts through a patent ductus arteriosus in preterm infants. As the authors note, an elevated pulmonary to systemic blood flow ratio (Qp/Qs) is an anatomically nonspecific reflection of a left-to-right shunt at either the ductal, atrial, or ventricular level. As pointed out in their paper, the six infants studied after surgical ligation of the ductus had a Q p / Q s ratio >1 (1.3 to 2.2), indicating a persistent L --~ R shunt. If foramen ovale shunts are quite common in the sick preterm infant, the lack of specificity of this technique seems to limit its usefulness. How can one be sure what component of an increased Q p / Q s ratio is related to the L ~ R P D A shunt vs the L ~ R atrial shunt? T h e authors suggest that a Q p / Q s ratio >2.2 is associated with a duetal shunt significant enough to require surgical ligation. These data appear to cl~flict with those presented by Serwer et a l ) In their study, 12 of 13 patients requiring surgical P D A ligation had a Q p / Q s <2.2 as measured by radionuclide technique. This is the level Vick et al. suggest as the upper limit of "normal" in their population. If one uses the data of Vick et al. to compare clinical evaluation with radionuclide angiography in establishing which patients with P D A require surgical ligation, a Q p / Q s >2.2, although more sensitiv•i proves to be no more specific than clinical evaluation alone (Table). Furthermore, a Q p / Q s >1 is even more nonspecific. Another point of concern is the inclusion of four clinically "asymptomatic" infants in the surgically ligated group. In the Methods section of the manuscript, Vick et al. define their study group as those preterm infants suspected of having significant shunting through a PDA. A P D A was defined as "clinically evident" when a m u r m u r was present, accompanied by bounding
Volume 103 Number 1
Editorial correspondence
Table. R e l a t i o n s h i p o f P D A r e q u i r i n g surgical ligation as p r e d i c t e d by clinical evaluation vs Q p / Q s ratio
Sensitivity* (%) Specificityt (%) Predictive accuracy of positive test:~
Clinical evaluation
Qp/Qs > 2.2
Qp/Qs > 1
76 68 50
94 69 80
100 15 61
(%) *True positives/(true positives + false negatives). ]'True negatives/(true negatives + false positives). ~True positives/(true positives + false positives).
pulses or cardiomegaly with pulmonary vascular engorgement on chest radiograph. Although Qp/Qs ratios are of interest in those four infants, they realty did not meet the author's criteria for selection for study, and technically should not be included in their analysis. Although provocative information is presented, use of this technique for aid in evaluation of the PDA shunt in preterm infants appears no more specific than clinical evaluation alone. Whether it may prove helpful in detecting the "silent" PDA will require further study. Dale C. Atverson, M.D. John D. Johnson, M.D. Lu-Ann Papile, M.D. Herbert Koffler, M.D. William Berman, Jr., M.D. University o f New Mexico Department o f Pediatrics School o f Medicine Albuquerque, N M 87131
REFERENCES
1.
2.
Vick GW III, Satterwhite C, Cassady G, Philips J, Yester MV, Logic JR: Radionuelide angiography in the evaluation of duetal shunts in preterm infants. J PEDIATR 101:264, 1982. Serwer GA, Armstrong BE, Anderson PAW: Continuous wave Doppler ultrasonographic quantitation of patent ductus arteriosus flow. J PEDIATR 100:297, 1982.
Repty To the Editor." Alverson et al. raise several interesting issues. Some we thought were discussed in our report; others, however, were not mentioned and deserve careful attention for proper use of radionuclide angiography in the diagnosis and management of patent ductus arteriosus in preterm infants, O f primary importance, we believe that "this method may be a valuable addition to other available diagnostic techniques . . . . " We do not propose that the radionuclide angiogram, or any other
17 3
single test, will accurately diagnose PDA in all preterm infants. A fundamental problem with this or any other method is the lack of an appropriate "gold standard." Even cardiac catheterization may not be totally reliable. Alverson et al. are correct in noting that the ratio of pulmonary to systemic blood flow (Qp/Qs), as determined by radionuclide angiography, is not diagnostic of the site of left-to-right shunting. However, the anatomically normal infant heart does not readily allow left-to-right foramen ovale shunting. The studies of Rudolph et al. 1 show that left-to-right foramen ovale shunts are uncommon in infants with respiratory distress syndrome. None of the infants in our study developed symptoms related to atrial or ventricular septal defects, and it seems reasonable to surmise that the left-to right shunts were largely caused by PDA. Alverson et al. discuss the discrepancy between Qp/Qs results as measured by our technique and that of Serwer et al? Several major differences between these two reports need to be highlighted. The study groups were vastly different. Serwer included 13 infants, 2 weeks to 9 years of age, only six of whom were born prematurely; our subjects were all premature, with 20 of 30 weighing ~<1250 gin, and 40 of the 55 studies were performed within seven days of birth. Second, our studies were performed using a mobile, single-crystal gamma camera (Ohio Nuclear Series 120), and a gamma-variate model 3'4 analysis was employed. This method uses the uptake portion and initial part of the downslope of the time-activity curve of the lung to predict the shape of the remainder of the curve, assuming no early tracer recirculation. Because our infants were small, we were able to analyze only a portion of the right lung in most studies. In nearly all cases, the heart was too large to permit uncontaminated analysis of left lung flow. Delays in count disappearance were assumed to result from left-to-right ductal shunting. In fact, tiny preterm infants have very rapid circulation times and abnormal lung time-activity curves, as compared with adults. The methods used by Serwer and associates were very different. They involved use of a stationary multicrystal gamma camera (Baird System Seventy-Seven), and analysis was based on the' assumption that indicator clearance from lung was an exponential function under normal conditions. They were also able to use summed counts from both lungs for their calculations. We studied a larger number of smaller, and presumably sicker, infants using methods not directly comparable with those of Serwer et al. We urge that any institution employing radionuclide angiography in PDA diagnosis develop its own set of standards based on its own experience. We chose the value of Qp/Qs >2.2 as abnormal, because 2.2 was the highest value obtained after PDA ligation in any subject. This value occurred in only one patient; all other scans after surgery had a Qp/Qs _<1.6. Subjects were studied when suspected of having significant PDA shunting by the classic clinical symptoms of murmur, bounding pulses, or cardiomegaly with pulmonary engorgement. Many infants have physiologically significant PDA shunts without these symptoms, so we also studied infants with prolonged ventilator dependence, unexplained high oxygen requirements, and persistent apnea and bradycardia. Any study that includes only infants with clinically evident PDA fails to explore the whole spectrum of the disorder.
E d i t o r i a l cor'respondence
The Journal o f Pediatrics July 1983
are not sufficiently aware of the initial symptoms of West syndrome. Too often the myoclonic jerks are attributed to fright or colic. 5. As to the importance of early therapy, Sorel was certainly the first to stress this. It was our aim to emphasize that once there is established brain damage and mental retardation resulting from infantile spasms (or preceding them), hormonal or any other therapy cannot be expected to reverse these. Hence the vital importance of treating patients before retardation develops. 6. We have observed in six patients that high doses of tetracosactrin significantly improved the mental status of patients who had previously been treated inadequately and who showed continuing spasms and no change in the EEG while receiving prolonged conventional treatment. Indeed, with our new protocol, spasms cease and the hypsarrhythmia resolves after the second injection of 1 mg tetracosactrin depot in almost every case. Since completion of our paper, we have treated another four patients with such results. These results are in contrast to those obtained in the 1960s, when 40 units A C T H were administered. In many of the patients receiving this treatment, spasms continued for weeks and mental recovery was rare. The full version of our paper included the details of these cases. 7. As to the hazards of A C T H therapy, it would appear from Riikonen's work, as well as from our own experience, that conventional doses are as dangerous as high doses. One way to minimize infections is not to hospitalize these patients during evaluation and therapy.
P. Lerman, M.D. Head EEG Laboratory Beilinson Medical Center Petak-Tiqua, Israel
Bone infarction in sickle cell disease To the Editor: I read with interest the article by Keeley and Buchanan. ~ They have attempted to separate, clinically, acute bone marrow infarcts without cortical involvement from cortical infarction with or without marrow involvement. They also address the problem of distinguishing between sterile bone infarcts and those complicated by osteomyelitis. In a recent monograph on this subject) I noted that "One large deficiency in approaching the problem of distinguishing between aseptic and septic bone infarcts is the lack of any large series of proven cases of aseptic cortical osteonecrosis of long bones." Keeley and Buchanan have now made a start in this direction. The authors misread the figures 3 when they stated that 50% of the cases I reviewed had "three-segment lesions." Actually it was stated that three-segment lesions generally seem to account for about 50% of the cases in Ibadan, but in my s ~ d y they constituted 32%. A chart (Fig. 2) indicated that 52 of 198 lesions (26%) were three-segment lesions. There are many possible reasons for differences between the two groups of patients, considering that one group is in West Africa and one is in the United States. The former frequently have
other medical problems, such as anemia from other causes, parasites, malaria, and malnutrition. Additionally, as the West African patients were younger, the periosteum could more easily be separated from the cortex to reveal a more extensive bone process radiographically. Even within the West African group, younger patients were found to have more three-segment lesions.
Stanley P. Bohrer, M.D., M.P.H. Bowman Gray School o f Medicine 300 S. Hawthorne Rd. Winston-Salem, N C 27103 REFERENCES 1. 2. 3.
Keetey K, Buchanan: Acute infarction of long bones in children with sickle cell anemia. J PEt)IATR 101:170, 1982. Bohrer SP: Bone ischemia and infarction in sickle ce!l disease. St. Louis, 1981, Warren H. Green, p 134. Bohrer SP: Acute long bone diaphyseal infarcts in sickle cell disease. Br J Radiol 43:685, 1970.
Radionuclide angiography in evaluation of PDA To the Editor: W e wish to comment on the article of Vick et al., Lregarding the use of radionuclide angiography in the evaluation of shunts through a patent ductus arteriosus in preterm infants. As the authors note, an elevated pulmonary to systemic blood flow ratio (Qp/Qs) is an anatomically nonspecific reflection of a left-to-right shunt at either the ductal, atrial, or ventricular level. As pointed out in their paper, the six infants studied after surgical ligation of the ductus had a Q p / Q s ratio >1 (1.3 to 2.2), indicating a persistent L --~ R shunt. If foramen ovale shunts are quite common in the sick preterm infant, the lack of specificity of this technique seems to limit its usefulness. How can one be sure what component of an increased Q p / Q s ratio is related to the L ~ R P D A shunt vs the L ~ R atrial shunt? T h e authors suggest that a Q p / Q s ratio >2.2 is associated with a duetal shunt significant enough to require surgical ligation. These data appear to cl~flict with those presented by Serwer et a l ) In their study, 12 of 13 patients requiring surgical P D A ligation had a Q p / Q s <2.2 as measured by radionuclide technique. This is the level Vick et al. suggest as the upper limit of "normal" in their population. If one uses the data of Vick et al. to compare clinical evaluation with radionuclide angiography in establishing which patients with P D A require surgical ligation, a Q p / Q s >2.2, although more sensitiv•i proves to be no more specific than clinical evaluation alone (Table). Furthermore, a Q p / Q s >1 is even more nonspecific. Another point of concern is the inclusion of four clinically "asymptomatic" infants in the surgically ligated group. In the Methods section of the manuscript, Vick et al. define their study group as those preterm infants suspected of having significant shunting through a PDA. A P D A was defined as "clinically evident" when a m u r m u r was present, accompanied by bounding
Volume 103 Number 1
Editorial correspondence
Table. R e l a t i o n s h i p o f P D A r e q u i r i n g surgical ligation as p r e d i c t e d by clinical evaluation vs Q p / Q s ratio
Sensitivity* (%) Specificityt (%) Predictive accuracy of positive test:~
Clinical evaluation
Qp/Qs > 2.2
Qp/Qs > 1
76 68 50
94 69 80
100 15 61
(%) *True positives/(true positives + false negatives). ]'True negatives/(true negatives + false positives). ~True positives/(true positives + false positives).
pulses or cardiomegaly with pulmonary vascular engorgement on chest radiograph. Although Qp/Qs ratios are of interest in those four infants, they realty did not meet the author's criteria for selection for study, and technically should not be included in their analysis. Although provocative information is presented, use of this technique for aid in evaluation of the PDA shunt in preterm infants appears no more specific than clinical evaluation alone. Whether it may prove helpful in detecting the "silent" PDA will require further study. Dale C. Atverson, M.D. John D. Johnson, M.D. Lu-Ann Papile, M.D. Herbert Koffler, M.D. William Berman, Jr., M.D. University o f New Mexico Department o f Pediatrics School o f Medicine Albuquerque, N M 87131
REFERENCES
1.
2.
Vick GW III, Satterwhite C, Cassady G, Philips J, Yester MV, Logic JR: Radionuelide angiography in the evaluation of duetal shunts in preterm infants. J PEDIATR 101:264, 1982. Serwer GA, Armstrong BE, Anderson PAW: Continuous wave Doppler ultrasonographic quantitation of patent ductus arteriosus flow. J PEDIATR 100:297, 1982.
Repty To the Editor." Alverson et al. raise several interesting issues. Some we thought were discussed in our report; others, however, were not mentioned and deserve careful attention for proper use of radionuclide angiography in the diagnosis and management of patent ductus arteriosus in preterm infants, O f primary importance, we believe that "this method may be a valuable addition to other available diagnostic techniques . . . . " We do not propose that the radionuclide angiogram, or any other
17 3
single test, will accurately diagnose PDA in all preterm infants. A fundamental problem with this or any other method is the lack of an appropriate "gold standard." Even cardiac catheterization may not be totally reliable. Alverson et al. are correct in noting that the ratio of pulmonary to systemic blood flow (Qp/Qs), as determined by radionuclide angiography, is not diagnostic of the site of left-to-right shunting. However, the anatomically normal infant heart does not readily allow left-to-right foramen ovale shunting. The studies of Rudolph et al. 1 show that left-to-right foramen ovale shunts are uncommon in infants with respiratory distress syndrome. None of the infants in our study developed symptoms related to atrial or ventricular septal defects, and it seems reasonable to surmise that the left-to right shunts were largely caused by PDA. Alverson et al. discuss the discrepancy between Qp/Qs results as measured by our technique and that of Serwer et al? Several major differences between these two reports need to be highlighted. The study groups were vastly different. Serwer included 13 infants, 2 weeks to 9 years of age, only six of whom were born prematurely; our subjects were all premature, with 20 of 30 weighing ~<1250 gin, and 40 of the 55 studies were performed within seven days of birth. Second, our studies were performed using a mobile, single-crystal gamma camera (Ohio Nuclear Series 120), and a gamma-variate model 3'4 analysis was employed. This method uses the uptake portion and initial part of the downslope of the time-activity curve of the lung to predict the shape of the remainder of the curve, assuming no early tracer recirculation. Because our infants were small, we were able to analyze only a portion of the right lung in most studies. In nearly all cases, the heart was too large to permit uncontaminated analysis of left lung flow. Delays in count disappearance were assumed to result from left-to-right ductal shunting. In fact, tiny preterm infants have very rapid circulation times and abnormal lung time-activity curves, as compared with adults. The methods used by Serwer and associates were very different. They involved use of a stationary multicrystal gamma camera (Baird System Seventy-Seven), and analysis was based on the' assumption that indicator clearance from lung was an exponential function under normal conditions. They were also able to use summed counts from both lungs for their calculations. We studied a larger number of smaller, and presumably sicker, infants using methods not directly comparable with those of Serwer et al. We urge that any institution employing radionuclide angiography in PDA diagnosis develop its own set of standards based on its own experience. We chose the value of Qp/Qs >2.2 as abnormal, because 2.2 was the highest value obtained after PDA ligation in any subject. This value occurred in only one patient; all other scans after surgery had a Qp/Qs _<1.6. Subjects were studied when suspected of having significant PDA shunting by the classic clinical symptoms of murmur, bounding pulses, or cardiomegaly with pulmonary engorgement. Many infants have physiologically significant PDA shunts without these symptoms, so we also studied infants with prolonged ventilator dependence, unexplained high oxygen requirements, and persistent apnea and bradycardia. Any study that includes only infants with clinically evident PDA fails to explore the whole spectrum of the disorder.