- Email: [email protected]
Neomycin Ototoxicity
395 Correspondence
during cardiopulmonary bypass. Surgery 80:266, (CP) levels are considerably different in the two 1976 groups reported while adenosine triphosphate (ATP) levels are essentially identical. No ready explanation 4. Engelman RM, Rousou JH, Auvil J: The safety of prolonged ischemic arrest using hypothermic carfor this discrepancy is available other than the most dioplegia. J Thorac Cardiovasc Surg 79:705, 1980 plausible one-that the two groups were not studied within the same time frame and reagent differences may have existed in the CP testing. The explanation Neomycin Ototoxicity given by Dr. Lolley of substrate deprivation in the To the Editor: low CP group does not hold up because All' control I was greatly interested in the report by Jonathan measurements in these same intermittent arrest ani- Meakins and Jean Allard entitled "Neomycin Abmals were essentially identical to those in the con- sorption following Clagett Procedure for Postpneutinuous arrest group. In order not to compare apples monectomy Empyema" (Ann Thorac Surg 29:32, with oranges, each group of animals was compared 1980). I am afraid, however, that the authors did with itself. As noted, in the continuous arrest group, not do their homework thoroughly enough with ATP fell 25% from control with reperfusion while CP specific reference to neomycin ototoxicity from refell 20% and with intermittent arrest, ATP fell 37% peated intrapleural irrigations. while CP fell 17%. No attempt was made to imply In 1971, I [6] wrote on empyema and alluded to 6 these changes were significant, which they obvi- personal patients who underwent successful closure ously are not, but the general trend with intermittent of postpneumonectomy empyema as originally dearrest (obvious in Figure 3 and 4) is for a declining scribed by Clagett and Geraci [l]; neomycin solution postreperfusion ATP and CP level with each succes- 0.25% was instilled only once at closure. In the same sive arrest, a sign of worsening metabolic reserve article, I discussed briefly the reports by Myerson with repeated reperfusion. and co-workers 151, Helm 121, Leach 131, and Melon Finally, and most important, what clinical impli- (41, each of whom described separate instances of secations accrue from this work? I believe one is that vere ototoxicity following repeated irrigations of neointermittent arrest with "inadequate" reperfusion is mycin. a poor preservation technique. This paper [l]and Over the intervening years, my associates and I others 12, 31 we have published previously would have had a 90% rate of success with approximately 15 support this. Indeed, in coronary revascularization postpneumonectomy empyemas closed after the procedures, we have been unable to correlate the du- manner of Clagett. There have been no instances of ration of cardioplegic arrest (even up to three hours) ototoxicity or renal toxicity. Because of the frequency with myocardial injury [4]. However, when massive of Staphylococcus aureus and pseudomonas infechypertrophy is present, as when multiple valves tions, we usually pack the opened cavity with gauze need replacing and revascularization is to be per- impregnated with citric acid. At closure, bacitracin formed, interrupting the arrest interval would seem and Coly-Mycin (colistin sulfate) are added to the prudent. However, the duration of intermittent re- 0.25% neomycin solution. perfusion should be appropriate to replace metaboIn 1972, Stafford and Clagett [7] reported their total lites and allow recovery of metabolic processes. How experience with 18 patients; ototoxic reactions devellong this should be and how best to accomplish it oped in none. Neomycin was used as an irrigant in remains a matter of investigation. only 1patient after open drainage, and shortly thereafter an itchy rash developed. The administration of Richard M . Engelman, M . D . neomycin was stopped promptly. Chief, Cardiac Surgery Meakins and Allard are entirely correct in stating Baystate Medical Center that no postoperative serum levels of neomycin have 759 Chestnut S t been previously.recorded. They have shown that, in Springfield, M A 01 107 general, serum levels less than 10 yg per milliliter do not cause toxic reactions. References I am not quite sure why Clagett and Geraci [l] de1. Engelman RM, Rousou JH, O'Donoghue MJ, et al: cided to use 0.25% neomycin for a one-time instillaA comparison of intermittent and continuous ar- tion. Perhaps it was a bit of serendipity, although rest for prolonged hypothermic cardioplegia. Ann they were well aware of the potentials of neomycin Thorac Surg 29:3, 1980 toxicity. In the article under discussion, perhaps it 2. Engelman RM, Adler A, Gouge TH, et al: The ef- was lucky that the authors were able to obtain negafect of normothermic anoxic arrest and ventricular tive cultures so quickly while irrigating with 1% fibrillation on the coronary blood flow distribu- neomycin solution. tion of the pig. J Thorac Cardiovasc Surg 692358, Paul C . Samson, M . D . 1975 3. Engelman RM, Chandra R, Baumann FG, et al: 3300 Webster St Myocardial reperfusion, a cause of ischemic injury Oakland, C A 94609
396 The Annals of Thoracic Surgery Vol 31 No 4 April 1981
References 1. Clagett OT, Geraci JE: A procedure for the management of postpneumonectomy empyema. J Thorac Cardiovasc Surg 45:141,1963 2. Helm WH: Ototoxicity of neomycin aerosol. Lancet 1:1294,1960 3. Leach W: Ototoxicity of neomycin and other antibiotics. J Laryngol Otol 76:744,1962 4. Melon J: Cited by Leach [3] 5. Myerson M, Knight HF, Gambarini AJ, Curran TL: Intrapleural neomycin causing ototoxicity. Ann Thorac Surg 9:483,1970 6. Samson PC: Empyema thoracis: essentials of present-day management. Ann Thorac Surg 11: 210, 1971 7. Stafford EG, Clagett OT: Postpneumonectomy empyema: neomycin instillation and definitive closure. J Thorac Cardiovasc Surg 63:771,1972
Reply To the Editor: We are grateful to Dr. Samson for pointing out the toxicity of neomycin when used in intrapleural irrigations. He supports our point of view nicely that neomycin is toxic and has produced complications in every clinical situation in which it has been employed. It is reasonable to assume that other antibiotics also will be absorbed in this setting. Therefore, Coly-Mycin, which is very nephrotoxic, must be used judiciously. Alteration in dosage is particularly important in patients with altered renal function. We do not wish to impugn in any way the Clagett procedure. It has made a major contribution to the management of postpneumonectomy empyema.
Jonathan L . Meakins, F.R.C.S.(C) Jean Allard, F.R.C.S.(C) Royal Victoria Hospital 687 Pine A v e West Montreal, Q u e , Canada H 3 A IAI
Location of LAD To the Editor: Dr. Fisk and associates are to be commended for reporting the clinical results of probe location of the left anterior descending artery (Ann Thorac Surg 29:480, 1980). Since the original report seven years ago, we have used this method more than forty times with no known adverse results.
In general, experienced surgeons have little difficulty isolating the proximal and middle segments of the left anterior descending artery, despite the fact that the vessel may be covered with a thick layer of fat and a variable amount of myocardium. The method described saves time and trauma to the heart if it is employed promptly whenever a difficult dissection is encountered. In some patients, this artery is in the septum proper at a depth below the cavity of the right ventricle. By incising directly onto a probe positioned within the anterior descending artery, it has been possible to expose the vessel without entering either of the ventricular chambers. In addition, seven or more years ago it was commonly believed that an arteriotomy and closure of a 1 mm coronary artery would be followed by a high incidence of occlusion of this vessel. The report of Dr. Fisk and colleagues and our own clinical experience support the view that this complication is unusual with modern techniques, magnification, and improved surgical skills.
George Robinson, M . D . Richard Brodman, M . D . Montefiore Hospital 1 1 1 E 210th S t Bronx, NY 10467
Identifying Proximal LAD To the Editor: Fisk and associates presented a reliable method of identifying the embedded proximal left anterior descending coronary artery (LAD) (Ann Thorac Surg 29:480, 1980). My colleagues and I have utilized a different approach to the identification of this artery because of the potential problems associated with primary closure of a coronary arteriotomy. In our experience, we have always been able to identify one or more diagonal branches of the LAD. With the aorta occluded and following infusion of cardioplegic solution, it is possible to trace a diagonal branch back to its origin from the LAD and prepare the LAD for anastomosis at this point. With magnification and a quiet, bloodless field, this dissection adds only a few minutes to the aortic crossclamp'time. In a five-month period, we utilized this approach in 5 patients; no excessive bleeding or perioperative infarctions occurred.
James P . Byrne, M . D . University of Kansas School of Medicine-Wichita 905 N Emporia Wichita, K S 67214
during cardiopulmonary bypass. Surgery 80:266, (CP) levels are considerably different in the two 1976 groups reported while adenosine triphosphate (ATP) levels are essentially identical. No ready explanation 4. Engelman RM, Rousou JH, Auvil J: The safety of prolonged ischemic arrest using hypothermic carfor this discrepancy is available other than the most dioplegia. J Thorac Cardiovasc Surg 79:705, 1980 plausible one-that the two groups were not studied within the same time frame and reagent differences may have existed in the CP testing. The explanation Neomycin Ototoxicity given by Dr. Lolley of substrate deprivation in the To the Editor: low CP group does not hold up because All' control I was greatly interested in the report by Jonathan measurements in these same intermittent arrest ani- Meakins and Jean Allard entitled "Neomycin Abmals were essentially identical to those in the con- sorption following Clagett Procedure for Postpneutinuous arrest group. In order not to compare apples monectomy Empyema" (Ann Thorac Surg 29:32, with oranges, each group of animals was compared 1980). I am afraid, however, that the authors did with itself. As noted, in the continuous arrest group, not do their homework thoroughly enough with ATP fell 25% from control with reperfusion while CP specific reference to neomycin ototoxicity from refell 20% and with intermittent arrest, ATP fell 37% peated intrapleural irrigations. while CP fell 17%. No attempt was made to imply In 1971, I [6] wrote on empyema and alluded to 6 these changes were significant, which they obvi- personal patients who underwent successful closure ously are not, but the general trend with intermittent of postpneumonectomy empyema as originally dearrest (obvious in Figure 3 and 4) is for a declining scribed by Clagett and Geraci [l]; neomycin solution postreperfusion ATP and CP level with each succes- 0.25% was instilled only once at closure. In the same sive arrest, a sign of worsening metabolic reserve article, I discussed briefly the reports by Myerson with repeated reperfusion. and co-workers 151, Helm 121, Leach 131, and Melon Finally, and most important, what clinical impli- (41, each of whom described separate instances of secations accrue from this work? I believe one is that vere ototoxicity following repeated irrigations of neointermittent arrest with "inadequate" reperfusion is mycin. a poor preservation technique. This paper [l]and Over the intervening years, my associates and I others 12, 31 we have published previously would have had a 90% rate of success with approximately 15 support this. Indeed, in coronary revascularization postpneumonectomy empyemas closed after the procedures, we have been unable to correlate the du- manner of Clagett. There have been no instances of ration of cardioplegic arrest (even up to three hours) ototoxicity or renal toxicity. Because of the frequency with myocardial injury [4]. However, when massive of Staphylococcus aureus and pseudomonas infechypertrophy is present, as when multiple valves tions, we usually pack the opened cavity with gauze need replacing and revascularization is to be per- impregnated with citric acid. At closure, bacitracin formed, interrupting the arrest interval would seem and Coly-Mycin (colistin sulfate) are added to the prudent. However, the duration of intermittent re- 0.25% neomycin solution. perfusion should be appropriate to replace metaboIn 1972, Stafford and Clagett [7] reported their total lites and allow recovery of metabolic processes. How experience with 18 patients; ototoxic reactions devellong this should be and how best to accomplish it oped in none. Neomycin was used as an irrigant in remains a matter of investigation. only 1patient after open drainage, and shortly thereafter an itchy rash developed. The administration of Richard M . Engelman, M . D . neomycin was stopped promptly. Chief, Cardiac Surgery Meakins and Allard are entirely correct in stating Baystate Medical Center that no postoperative serum levels of neomycin have 759 Chestnut S t been previously.recorded. They have shown that, in Springfield, M A 01 107 general, serum levels less than 10 yg per milliliter do not cause toxic reactions. References I am not quite sure why Clagett and Geraci [l] de1. Engelman RM, Rousou JH, O'Donoghue MJ, et al: cided to use 0.25% neomycin for a one-time instillaA comparison of intermittent and continuous ar- tion. Perhaps it was a bit of serendipity, although rest for prolonged hypothermic cardioplegia. Ann they were well aware of the potentials of neomycin Thorac Surg 29:3, 1980 toxicity. In the article under discussion, perhaps it 2. Engelman RM, Adler A, Gouge TH, et al: The ef- was lucky that the authors were able to obtain negafect of normothermic anoxic arrest and ventricular tive cultures so quickly while irrigating with 1% fibrillation on the coronary blood flow distribu- neomycin solution. tion of the pig. J Thorac Cardiovasc Surg 692358, Paul C . Samson, M . D . 1975 3. Engelman RM, Chandra R, Baumann FG, et al: 3300 Webster St Myocardial reperfusion, a cause of ischemic injury Oakland, C A 94609
396 The Annals of Thoracic Surgery Vol 31 No 4 April 1981
References 1. Clagett OT, Geraci JE: A procedure for the management of postpneumonectomy empyema. J Thorac Cardiovasc Surg 45:141,1963 2. Helm WH: Ototoxicity of neomycin aerosol. Lancet 1:1294,1960 3. Leach W: Ototoxicity of neomycin and other antibiotics. J Laryngol Otol 76:744,1962 4. Melon J: Cited by Leach [3] 5. Myerson M, Knight HF, Gambarini AJ, Curran TL: Intrapleural neomycin causing ototoxicity. Ann Thorac Surg 9:483,1970 6. Samson PC: Empyema thoracis: essentials of present-day management. Ann Thorac Surg 11: 210, 1971 7. Stafford EG, Clagett OT: Postpneumonectomy empyema: neomycin instillation and definitive closure. J Thorac Cardiovasc Surg 63:771,1972
Reply To the Editor: We are grateful to Dr. Samson for pointing out the toxicity of neomycin when used in intrapleural irrigations. He supports our point of view nicely that neomycin is toxic and has produced complications in every clinical situation in which it has been employed. It is reasonable to assume that other antibiotics also will be absorbed in this setting. Therefore, Coly-Mycin, which is very nephrotoxic, must be used judiciously. Alteration in dosage is particularly important in patients with altered renal function. We do not wish to impugn in any way the Clagett procedure. It has made a major contribution to the management of postpneumonectomy empyema.
Jonathan L . Meakins, F.R.C.S.(C) Jean Allard, F.R.C.S.(C) Royal Victoria Hospital 687 Pine A v e West Montreal, Q u e , Canada H 3 A IAI
Location of LAD To the Editor: Dr. Fisk and associates are to be commended for reporting the clinical results of probe location of the left anterior descending artery (Ann Thorac Surg 29:480, 1980). Since the original report seven years ago, we have used this method more than forty times with no known adverse results.
In general, experienced surgeons have little difficulty isolating the proximal and middle segments of the left anterior descending artery, despite the fact that the vessel may be covered with a thick layer of fat and a variable amount of myocardium. The method described saves time and trauma to the heart if it is employed promptly whenever a difficult dissection is encountered. In some patients, this artery is in the septum proper at a depth below the cavity of the right ventricle. By incising directly onto a probe positioned within the anterior descending artery, it has been possible to expose the vessel without entering either of the ventricular chambers. In addition, seven or more years ago it was commonly believed that an arteriotomy and closure of a 1 mm coronary artery would be followed by a high incidence of occlusion of this vessel. The report of Dr. Fisk and colleagues and our own clinical experience support the view that this complication is unusual with modern techniques, magnification, and improved surgical skills.
George Robinson, M . D . Richard Brodman, M . D . Montefiore Hospital 1 1 1 E 210th S t Bronx, NY 10467
Identifying Proximal LAD To the Editor: Fisk and associates presented a reliable method of identifying the embedded proximal left anterior descending coronary artery (LAD) (Ann Thorac Surg 29:480, 1980). My colleagues and I have utilized a different approach to the identification of this artery because of the potential problems associated with primary closure of a coronary arteriotomy. In our experience, we have always been able to identify one or more diagonal branches of the LAD. With the aorta occluded and following infusion of cardioplegic solution, it is possible to trace a diagonal branch back to its origin from the LAD and prepare the LAD for anastomosis at this point. With magnification and a quiet, bloodless field, this dissection adds only a few minutes to the aortic crossclamp'time. In a five-month period, we utilized this approach in 5 patients; no excessive bleeding or perioperative infarctions occurred.
James P . Byrne, M . D . University of Kansas School of Medicine-Wichita 905 N Emporia Wichita, K S 67214