- Email: [email protected]
Tissue Adhesives
CORRESPONDENCE
1. Ellis GL, Ddaney J, Dehart DA, et aI: The efficacy of metodopramide in the treatment of migraine headache. Ann Emerg Med 199.3;22:191-195. 2. KlapperJA, 5tanton J: Current emergency treatment of severe migraine headache. Headache 199.3;33:560-562. 3.5aadah HA: Abortive migraine therapy in the office with dexamethasone and prochlorperazine. Headache 1994;34:366-370. 4. Catlaham M, Raskin N: A controlledstudy of dihydroergotamine in the treatment of acute migraine headache. Headache 1986;26:168-i 71. 5. JonesJ, Sklar D, DoughertyJ, et al: Randomized doubleblind trial of intravenous prochlorperazinefor the treatment of acute headache.JAMA i989;26I :i 174-1175. 6. YeaIy DM: Ketorolacin the treatment of acute pain: The pendulum swings.Ann Emerg Med 1992;21:985-986. 7. The Multinational Oral 5umatriptan and C@rgot Comparative Study Group: A randomized double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. Eur Neurol 1991;31:314-322. 8. Akpunona BE, Mutgi AB, Federman DJ, et al: Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: A multicenter trial. Ann Emerg Meal 1995;25:464-469. 9. Bell R, Montoya D, 5huaib A, et aI: A comparative trial of three agents in the treatment of acute migraine headache. Ann Emerg Med 1990;19:1079-1982. i0. 5tMl IG, Dufour DG, Moher D, et al: Methotrimeprazine versus meperidine and dimenhydrinate in the treatment of severe migraine:A randomized, controlled trial. Ann Emerg Med 1991;20:1201-1205.
In reply." We thank Ducharme and Beveridge for their interest in our manuscript and a recent editorial. We agree that much pain-management research is hindered by various flaws in design and analysis. However, we are puzzled by the letter in that all of the contentions stated by Ducharme and Beveridge are already clearly illustrated in our manuscript. We take this opportunity to reiterate our views and to clarify some issues raised by the authors. We stated in the manuscript that prochlorperazine and metoclopramide were superior only in the initial treatment of migraine headache in the emergency department. We also stated that follow-up was a major limitation of our study. We believe this limitation is overcome by the definition of a priori clinically acceptable relative and absolute measurement criteria for the relief of pain. In the editorial we discussed the use of opioids as the gold standard of analgesia. We noted that the dose-response curve for initial short-term analgesia differed from that of nonsteroidal antiinflammatory drugs (NSAIDs). With opioids, a diagonal to curved response is seen with both analgesia and side effects, especially sedation, whereas with NSAIDs the analgesia dose-response curve flattens out
53 0
quickly; side effects are near zero until very high single doses are used. The analgesic dose-response curves for promethazine and metoclopramide are unknown but are likely a combination of both the opioid and NSAID curves. Furthermore, although higher doses of promethazine and metoclopramide can be used for nausea, the same or lower doses are used in headache. Therefore for our trial we chose doses that had been clinically successful in previous work. The doses of promethazine and metoclopramide in other situations, such as nausea in chemotherapy, are not germane to this discussion. As we stated in our manuscript, follow-up research is necessary, especially to define dose response, long-term effects, and side effects. Nonetheless, our data are convincing of the superiority of promethazine over metoclopramide in the initial treatment of migraine headache in the ED.
Marco Coppola,DO Departmentof EmergencyMedicine DamallArmy CommunityHospital Fort Hood, Texas TexasA&M UniversityHealth ScienceCenter Houston, Texas DonaldM Yealy,MD RobertA Leibold, MD Departmentof EmergencyMedicine Universityof Pittsburgh Pittsburgh, Pennsylvania
Tissue Adhesives To the Editor. I read with interest the recent Annalsarticle comparing the tensile strength of cyanoacrylate and suture laceration closures [November 1995;16:575-578]. The results appear to support the current practice of limiting adhesive closure to those areas subject to a minimum of stress across the wound surface. I am at a loss to understand why breaking strength and tension were reported in grams throughout the manuscript. The tensiometer was calibrated in gram intervals; however, force should have been calculated by the multiplication of unit mass (grams) by 981 cm/sec 2, the acceleration due to gravity. Force is presented in dynes or newtons,
depending on whether one is working in the CGS or MKS system, respectively. 1 The mean breaking tensile "strength" for albino guinea pigs treated with tissue adhesive alone was 1.84 newtons. This value is quite low and, alone, difficult to interpret because the cross-sectional area in the model has been neither fixed nor reported. The tensile strength of skin typically ranges from 2.5x108 to 16xl 06 newtons/m2. 2 All epidermal stress-strain relationships and strengths are best presented as force divided by controlled cross-sectional dimensions. As a result, it is difficult to compare the results in this paper with those of other studies. 3 In addition, some effort should have been made to identify areas on a guinea pig analogous to Langer's cleavage lines on the human face. The definition of Langer's lines is based on those circular punctures that produce elliptical holes in the skin.2 Directional variability of in vivo tension is well documented for the human subject and would have been best extrapolated to some part of the guinea pig model. Inflicted experimental wounds perpendicular to Langers' lines will bear the greatest stress. Can we assume that each of the four wounds per animal in the Bresnahan study possessed the same orientation to these lines of stress? Finally, the small numbers of subjects and the large variation in breaking "strength" for each type of closure lead one to wonder whether the power of the study was sufficient for the authors to draw the conclusions they did. The model in this paper was too limited to permit the distinction between force and stress. As a result, few if any extrapolations to a human model can be made, limiting the usefulness of this report.
GregoryD Jay, MD, PhD Departmentof EmergencyMedicine RhodeIslandHospital Providence,RhodeIsland I. Weber E: Physical units and standards, in Eshbach W, Souders M (eds): Handbook of Engineering Fundamentals. New York:John Wiley & Sons, 1975:385427. 2. Lanir Y: Skin mechanics, in 5haIak R, Chien 5 (eds): Handbook of Bioengineering. New York: McGraw-Hill, 1987:1i.i-ii.25. 3. Yaron M, Halperin M, Hufjkr W, et aI: Preliminary reports: Efficacy of tissue gluefor laceration repair in art animal model. Acad Emerg Meal i995;4:259-263.
ANNALS OF EMERGENCY MEDICINE
27:4 APRIL 1996
CORRESPONDENCE
To the Editor. I read with interest the article by Bresnahan, Howell, and Wizorek [November 1995116:575578] on the tensile :strength of tissue adhesives. My clinical experience and research with tissue adhesives leads me to question some of their conclusions and methods. 14 The authors' results differ from those of two earlier studies in which the tensile strength of tissue of adhesives was compared with that of sutures.4.5 These studies showed a difference in earl,/tensile strength but no difference at day 7 or day 20. Perhaps the tensile strength would have been the same had it been measured at day 7 and not day 4. It is also not apparent from the description of methods whether the skin sutures were still in place on day 4. This leads us to the question of clinical importance of these findings. The reason tissue adhesives are not recommended for areas under high tensile stress is the low tensile strength of tissue adhesives in the first 24 to 48 hours, when wound healing has yet to become significant and tensile strength is at its lowest. 4 Logic dictates that if a wound-closure technique fails, it will most likely do so at the time of its lowest tensile strength. From my clinical and basic science experience, the conclusions made by these investigators are correct. ~,4 However, their findings of tensile strength at day 4 add little evidence to support these conclusions. Future animal models should be designed to determine the minimal tensile strength needed in different areas of the body to prevent wounds from dehiscing. The authors also make an inaccurate assumption that all cyanoacrylate adhesives are the same. Nexaband liquid, used in this study, is a veterinary product that has never been approved for use or used in a study of human subjects. It has several formulations for cat declawing, skin closure, and spray bandaging. Each formulation varies in the combination of n-butyicyanoacrylate monomer, stabilizers, plasticizers, and dyes (personal communication, JG Clark, November 1995). Each formulation has different properties, tensile strength, and indications. It is probably not appropriate to compare it with Histoacryl Blue, a relatively pure n-2-butylcyanoacrylate monomer that has been studied clinically.
APRIL 1996
27:4
ANNALS OF EMERGENCY MEDICINE
Finally, a topical octylcyanoacrylate formula has been developed for skin closure and is soon to start US Food and Drug Administration clinical trials. This tissue adhesive formulation has several properties that may make it more clinically useful than the pure n-butylcyanoacrylate monomer. We are evaluating the clinical performance and indications for this new cyanoacrylate adhesive at our institution.
Jim @inn, MD Division of EmergencyMedicine University of Ottawa Ottawa General Hospital Ottawa, Ontario, Canada [Editor's note: Dr Ouinn has a relationship with Tripoint Medical the manufacturer of the octy/cyanoacrylate adhesive he is testing and of the product used by Bresnahan, Howell, and Wizorek in their study. Although Tripoint Medical is funding research by Dr @inn, he has no financial association with this or any companyinvolved with cyanoacry/ate adhesives.] I. ~uinn JV, Drzewiecki A, Li MM, et al: A randomized, controlled trial comparing a tissue adhesive with suturi7N in the repair of pediatric facial lacerations. Ann Emerg Med 1993122:1130-1135. 2. Quinn JV, Nssiclt J: Tissue adhesives for laceration repair during sporting events. ClinJ Sport Med 199414:245-248. 3. Quinn JV, Osmond MS, Yurach J, et aI: Histoa
Rebuilding in Bosnia To the Editor. Greetings from Bosnia. Our emergency medicine team, based in Zenica, just received the September 1995 issue of Annals. It gave us all great pleasure and also provided a sense of satisfaction to see the newly introduced International Reports section. We know from experience that emergency medicine is truly a global specialty, and we strongly believe it should be recognized as such. It is our opinion that the concepts of the specialty, which have proved so valuable in the United States over the past few decades, are univer-
sally adaptable. With proper emergency health policy guidance, combined with intensive physician/nurse training programs, no country's citizens should die unnecessarily or be needlessly subjected to lifelong disability as a result of the absence of emergency care or dated, ineffective systems. Since 1993, the International Medical Corps (IMC)--a nonprofit, nonsectarian humanitarian aid organization based in Los Angeles-has been involved in the development of a modern emergency health care system in central Bosnia. Soon the rebuilding and rehabilitation of Bosnia's hospitals and clinics must start. The replenishment of depleted medical stocks and replacement of overused, aged equipment must also be achieved. Although these services are desperately needed, one of IMC's greatest concerns is that the education of Bosnia's health care providers will not parallel the physical rebuilding of the health care infrastructure. If this proves true, who will work in the renovated facilities and operate the new technology, and what level of care will be delivered to the population of Bosnia? For this reason, fMC is focusing on educating young physicians and nurses in emergency medicine. In 2 years, the Zenica Hospital emergency department has evolved from a two-bed temporary facility to a 15-bed facility including a two-bed trauma and critical care area. More than 20,000 patients have been evaluated in the ED in the past 22 months by the seven Bosnian physicians and 21 nurses training in the department. In the first 10 months of I995, 1,800 war-related trauma cases {both civilian and military] were cared for. All patient visits are thoroughly documented, and for the past 7 months a monthly database has been generated. This database serves not only as a documentation tool but as a valuable source of epidemiologic information and inventory use records. All data entry is the responsibility of the Bosnian nursing staff. A 4-year physician emergency specialization curriculum and a 6-month emergency nursing curriculum have been developed; both have served as teaching guidelines for the approximately 25 program volunteers, all emergency medicine specialists from the United States and Australia, who serve as formal lecturers and bedside mentors to the Bosnian ED staff. The long-term IMC staff members are also all
53 1
1. Ellis GL, Ddaney J, Dehart DA, et aI: The efficacy of metodopramide in the treatment of migraine headache. Ann Emerg Med 199.3;22:191-195. 2. KlapperJA, 5tanton J: Current emergency treatment of severe migraine headache. Headache 199.3;33:560-562. 3.5aadah HA: Abortive migraine therapy in the office with dexamethasone and prochlorperazine. Headache 1994;34:366-370. 4. Catlaham M, Raskin N: A controlledstudy of dihydroergotamine in the treatment of acute migraine headache. Headache 1986;26:168-i 71. 5. JonesJ, Sklar D, DoughertyJ, et al: Randomized doubleblind trial of intravenous prochlorperazinefor the treatment of acute headache.JAMA i989;26I :i 174-1175. 6. YeaIy DM: Ketorolacin the treatment of acute pain: The pendulum swings.Ann Emerg Med 1992;21:985-986. 7. The Multinational Oral 5umatriptan and C@rgot Comparative Study Group: A randomized double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. Eur Neurol 1991;31:314-322. 8. Akpunona BE, Mutgi AB, Federman DJ, et al: Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: A multicenter trial. Ann Emerg Meal 1995;25:464-469. 9. Bell R, Montoya D, 5huaib A, et aI: A comparative trial of three agents in the treatment of acute migraine headache. Ann Emerg Med 1990;19:1079-1982. i0. 5tMl IG, Dufour DG, Moher D, et al: Methotrimeprazine versus meperidine and dimenhydrinate in the treatment of severe migraine:A randomized, controlled trial. Ann Emerg Med 1991;20:1201-1205.
In reply." We thank Ducharme and Beveridge for their interest in our manuscript and a recent editorial. We agree that much pain-management research is hindered by various flaws in design and analysis. However, we are puzzled by the letter in that all of the contentions stated by Ducharme and Beveridge are already clearly illustrated in our manuscript. We take this opportunity to reiterate our views and to clarify some issues raised by the authors. We stated in the manuscript that prochlorperazine and metoclopramide were superior only in the initial treatment of migraine headache in the emergency department. We also stated that follow-up was a major limitation of our study. We believe this limitation is overcome by the definition of a priori clinically acceptable relative and absolute measurement criteria for the relief of pain. In the editorial we discussed the use of opioids as the gold standard of analgesia. We noted that the dose-response curve for initial short-term analgesia differed from that of nonsteroidal antiinflammatory drugs (NSAIDs). With opioids, a diagonal to curved response is seen with both analgesia and side effects, especially sedation, whereas with NSAIDs the analgesia dose-response curve flattens out
53 0
quickly; side effects are near zero until very high single doses are used. The analgesic dose-response curves for promethazine and metoclopramide are unknown but are likely a combination of both the opioid and NSAID curves. Furthermore, although higher doses of promethazine and metoclopramide can be used for nausea, the same or lower doses are used in headache. Therefore for our trial we chose doses that had been clinically successful in previous work. The doses of promethazine and metoclopramide in other situations, such as nausea in chemotherapy, are not germane to this discussion. As we stated in our manuscript, follow-up research is necessary, especially to define dose response, long-term effects, and side effects. Nonetheless, our data are convincing of the superiority of promethazine over metoclopramide in the initial treatment of migraine headache in the ED.
Marco Coppola,DO Departmentof EmergencyMedicine DamallArmy CommunityHospital Fort Hood, Texas TexasA&M UniversityHealth ScienceCenter Houston, Texas DonaldM Yealy,MD RobertA Leibold, MD Departmentof EmergencyMedicine Universityof Pittsburgh Pittsburgh, Pennsylvania
Tissue Adhesives To the Editor. I read with interest the recent Annalsarticle comparing the tensile strength of cyanoacrylate and suture laceration closures [November 1995;16:575-578]. The results appear to support the current practice of limiting adhesive closure to those areas subject to a minimum of stress across the wound surface. I am at a loss to understand why breaking strength and tension were reported in grams throughout the manuscript. The tensiometer was calibrated in gram intervals; however, force should have been calculated by the multiplication of unit mass (grams) by 981 cm/sec 2, the acceleration due to gravity. Force is presented in dynes or newtons,
depending on whether one is working in the CGS or MKS system, respectively. 1 The mean breaking tensile "strength" for albino guinea pigs treated with tissue adhesive alone was 1.84 newtons. This value is quite low and, alone, difficult to interpret because the cross-sectional area in the model has been neither fixed nor reported. The tensile strength of skin typically ranges from 2.5x108 to 16xl 06 newtons/m2. 2 All epidermal stress-strain relationships and strengths are best presented as force divided by controlled cross-sectional dimensions. As a result, it is difficult to compare the results in this paper with those of other studies. 3 In addition, some effort should have been made to identify areas on a guinea pig analogous to Langer's cleavage lines on the human face. The definition of Langer's lines is based on those circular punctures that produce elliptical holes in the skin.2 Directional variability of in vivo tension is well documented for the human subject and would have been best extrapolated to some part of the guinea pig model. Inflicted experimental wounds perpendicular to Langers' lines will bear the greatest stress. Can we assume that each of the four wounds per animal in the Bresnahan study possessed the same orientation to these lines of stress? Finally, the small numbers of subjects and the large variation in breaking "strength" for each type of closure lead one to wonder whether the power of the study was sufficient for the authors to draw the conclusions they did. The model in this paper was too limited to permit the distinction between force and stress. As a result, few if any extrapolations to a human model can be made, limiting the usefulness of this report.
GregoryD Jay, MD, PhD Departmentof EmergencyMedicine RhodeIslandHospital Providence,RhodeIsland I. Weber E: Physical units and standards, in Eshbach W, Souders M (eds): Handbook of Engineering Fundamentals. New York:John Wiley & Sons, 1975:385427. 2. Lanir Y: Skin mechanics, in 5haIak R, Chien 5 (eds): Handbook of Bioengineering. New York: McGraw-Hill, 1987:1i.i-ii.25. 3. Yaron M, Halperin M, Hufjkr W, et aI: Preliminary reports: Efficacy of tissue gluefor laceration repair in art animal model. Acad Emerg Meal i995;4:259-263.
ANNALS OF EMERGENCY MEDICINE
27:4 APRIL 1996
CORRESPONDENCE
To the Editor. I read with interest the article by Bresnahan, Howell, and Wizorek [November 1995116:575578] on the tensile :strength of tissue adhesives. My clinical experience and research with tissue adhesives leads me to question some of their conclusions and methods. 14 The authors' results differ from those of two earlier studies in which the tensile strength of tissue of adhesives was compared with that of sutures.4.5 These studies showed a difference in earl,/tensile strength but no difference at day 7 or day 20. Perhaps the tensile strength would have been the same had it been measured at day 7 and not day 4. It is also not apparent from the description of methods whether the skin sutures were still in place on day 4. This leads us to the question of clinical importance of these findings. The reason tissue adhesives are not recommended for areas under high tensile stress is the low tensile strength of tissue adhesives in the first 24 to 48 hours, when wound healing has yet to become significant and tensile strength is at its lowest. 4 Logic dictates that if a wound-closure technique fails, it will most likely do so at the time of its lowest tensile strength. From my clinical and basic science experience, the conclusions made by these investigators are correct. ~,4 However, their findings of tensile strength at day 4 add little evidence to support these conclusions. Future animal models should be designed to determine the minimal tensile strength needed in different areas of the body to prevent wounds from dehiscing. The authors also make an inaccurate assumption that all cyanoacrylate adhesives are the same. Nexaband liquid, used in this study, is a veterinary product that has never been approved for use or used in a study of human subjects. It has several formulations for cat declawing, skin closure, and spray bandaging. Each formulation varies in the combination of n-butyicyanoacrylate monomer, stabilizers, plasticizers, and dyes (personal communication, JG Clark, November 1995). Each formulation has different properties, tensile strength, and indications. It is probably not appropriate to compare it with Histoacryl Blue, a relatively pure n-2-butylcyanoacrylate monomer that has been studied clinically.
APRIL 1996
27:4
ANNALS OF EMERGENCY MEDICINE
Finally, a topical octylcyanoacrylate formula has been developed for skin closure and is soon to start US Food and Drug Administration clinical trials. This tissue adhesive formulation has several properties that may make it more clinically useful than the pure n-butylcyanoacrylate monomer. We are evaluating the clinical performance and indications for this new cyanoacrylate adhesive at our institution.
Jim @inn, MD Division of EmergencyMedicine University of Ottawa Ottawa General Hospital Ottawa, Ontario, Canada [Editor's note: Dr Ouinn has a relationship with Tripoint Medical the manufacturer of the octy/cyanoacrylate adhesive he is testing and of the product used by Bresnahan, Howell, and Wizorek in their study. Although Tripoint Medical is funding research by Dr @inn, he has no financial association with this or any companyinvolved with cyanoacry/ate adhesives.] I. ~uinn JV, Drzewiecki A, Li MM, et al: A randomized, controlled trial comparing a tissue adhesive with suturi7N in the repair of pediatric facial lacerations. Ann Emerg Med 1993122:1130-1135. 2. Quinn JV, Nssiclt J: Tissue adhesives for laceration repair during sporting events. ClinJ Sport Med 199414:245-248. 3. Quinn JV, Osmond MS, Yurach J, et aI: Histoa
Rebuilding in Bosnia To the Editor. Greetings from Bosnia. Our emergency medicine team, based in Zenica, just received the September 1995 issue of Annals. It gave us all great pleasure and also provided a sense of satisfaction to see the newly introduced International Reports section. We know from experience that emergency medicine is truly a global specialty, and we strongly believe it should be recognized as such. It is our opinion that the concepts of the specialty, which have proved so valuable in the United States over the past few decades, are univer-
sally adaptable. With proper emergency health policy guidance, combined with intensive physician/nurse training programs, no country's citizens should die unnecessarily or be needlessly subjected to lifelong disability as a result of the absence of emergency care or dated, ineffective systems. Since 1993, the International Medical Corps (IMC)--a nonprofit, nonsectarian humanitarian aid organization based in Los Angeles-has been involved in the development of a modern emergency health care system in central Bosnia. Soon the rebuilding and rehabilitation of Bosnia's hospitals and clinics must start. The replenishment of depleted medical stocks and replacement of overused, aged equipment must also be achieved. Although these services are desperately needed, one of IMC's greatest concerns is that the education of Bosnia's health care providers will not parallel the physical rebuilding of the health care infrastructure. If this proves true, who will work in the renovated facilities and operate the new technology, and what level of care will be delivered to the population of Bosnia? For this reason, fMC is focusing on educating young physicians and nurses in emergency medicine. In 2 years, the Zenica Hospital emergency department has evolved from a two-bed temporary facility to a 15-bed facility including a two-bed trauma and critical care area. More than 20,000 patients have been evaluated in the ED in the past 22 months by the seven Bosnian physicians and 21 nurses training in the department. In the first 10 months of I995, 1,800 war-related trauma cases {both civilian and military] were cared for. All patient visits are thoroughly documented, and for the past 7 months a monthly database has been generated. This database serves not only as a documentation tool but as a valuable source of epidemiologic information and inventory use records. All data entry is the responsibility of the Bosnian nursing staff. A 4-year physician emergency specialization curriculum and a 6-month emergency nursing curriculum have been developed; both have served as teaching guidelines for the approximately 25 program volunteers, all emergency medicine specialists from the United States and Australia, who serve as formal lecturers and bedside mentors to the Bosnian ED staff. The long-term IMC staff members are also all
53 1