If you wish to respond to a paper or other item already published in the BJA, please go to the abstract/full text version of that item and click on the link "E-Letters: Submit a response to the article".
Electronic Letters to:
|
|
E-letters: Electronic letters published:
-
![[Read E-letter]](/icons/misc/sectionDOWN.gif)
Conflicts of interest between the academic aspirations of faculty in private and state universities in Massachusetts.
- Richard G Fiddian-Green (21 July 2009)
-
Lymphatic flow rate and risk of early lung allograft dysfunction.
- Richard G Fiddian-Green (16 July 2009)
-
Blood volume and the preservation of adenine nucleotide pools.
- Richard G Fiddian-Green (14 April 2009)
-
Professor Peart's opinion of fluid management in our surgical unit.
- Richard G Fiddian-Green (14 April 2009)
-
Fluid volumes and the preservation of adenine nucleotide pools
- David R McIlroy, David V. Pilcher, Greg I. Snell (7 April 2009)
-
Fluid volumes and the preservation of adenine nucleotide pools.
- Richard G Fiddian-Green (1 April 2009)
|
|
|||
|
Richard G Fiddian-Green, FRCS, FACS None
Send letter to journal:
|
It should be added that in studies performed by Salzman et al (1) permeability was assessed in anesthetized pigs "by measuring the plasma-to -lumen clearance of fluorescein isothiocyanate dextran (4,000 Da; FD-4) by a segment of ileum perfused with Ringer lactate solution. Mucosal perfusion permeability were linearly correlated with mucosal [H+] in animals subjected to graded degrees of mechanically induced mesenteric ischemia (n = 14, R2 = 0.58, P < 0.002) or injected with graded doses of LPS (n = 11, R2 = 0.93, P < 0.0001)". If true in humans having surgery the findings are especially relevant to the hypothesis that pulmonary dysfunction is a function of gastric intramucosal pH and primarily the product of translocation into lymphatic channels draining directly into the pulmonary circulation. It might be relevant to add that Salzman challenged my tonometric patents, a challenge was settled in my favour in 1999(2). Furthermore I, as a faculty member of a state university, the University of Massachusetts, had been advised to resign my academic appointment to avoid having conflict of interest because of my widely disclosed commerical associations, a criminal offense for a state employee. This did not apply to Salzman at al for Harvard is not a state university. 1. A. L. Salzman, H. Wang, P. S. Wollert, T. J. Vandermeer, C. C. Compton, A. G. Denenberg and M. P. Fink. Endotoxin-induced ileal mucosal hyperpermeability in pigs: role of tissue acidosis. Am J Physiol Gastrointest Liver Physiol 266: G633-G646, 1994. 2. SALZMAN et al. V. FIDDIAN-GREEN - law.onecle.com/board-of-patent-appeals/.../ja103939005.html Conflict of Interest:Tonometric patents issued in my name. |
|||
|
|
|||
|
Richard G Fiddian-Green, FRCS, FACS None
Send letter to journal:
|
The inverse relationship between volume of intraoperative colloid and early lung allograft function might be a function of lymphatic flow rate. Lymphatic flow rate increases by a much as a factor of 20 as interstital pressure rises due to the accumulation of interstitial fluid (1). Lymph bypasses the liver and enters the pulmonary circulation directly via the thoracic duct. This lymph has the potential to increase the risk of pulmonary injury, relative to hepatic injury, known to be induced by ischemia-reperfusion injury of gut mucosa in an animal model (2) because it is not filtered by the liver and Kupfer cells. Gut mucosal injury is known to be associated with the translocation of endotoxin, cytokine release and the translocation of enteric bacteria. In this animal model "Gastric intramucosal pH was [also] significantly decreased..Furthermore, an increase in gastric intramucosal hydrogen ion concentration was associated with a concomitant increase in tissue injury, a presumed harbinger of multiple organ failure". These findings are consistent with those in our earlier clinical study of nosocomial pneumonia in 62 ICU patients. "The best stand-alone predictors for nosocomial pneumonia were bleeding from stress ulceration (p<0.001), the severity of illness present (p<0.001), and intramucosal acidosis in the stomach (p = .023), a metabolic indication of mucosal ischemia. Mechanical ventilation (p = .038) and the administration of antacids/cimetidine (p = .054) were also of stand-alone predictive value, but did not significantly improve the best predictive model for nosocomial pneumonia derived from the severity of illness present and the intramucosal pH in the stomach" (3). Lymphatic flow rate is likely to increase in proportion with the volume of crystalloid administered. Intraoperative volume expansion with colloid might attenuate this effect but would not eliminate it if intravascular fluid pressure and capillary permeability are also increased, as is very likely in those whose gastric intramucosal pH falls to abnormally low levels. If so preventing the development of a gastric intramucosal acidosis and shifting translocation from lymph to portal venous blood by using the gastric intramucosal pH to restrict transfusion needs should be accompanied by a reduced risk of early lung allograft dysfunction. 1. Guyton & Hall: Textbook of Medical Physiology 11th edition. 2. Nielsen, Vance G. MD; Tan, Sidhartha MD; Baird, Manuel S. MS; McCammon, Andrew T. MSEE; Parks, Dale A. PhD Gastric intramucosal pH and multiple organ injury: Impact of ischemia-reperfusion and xanthine oxidase. Critical Care Medicine: August 1996 - Volume 24 - Issue 8 - pp 1339-1344 3. FIDDIAN-GREEN, RICHARD G. MA, BM, BCH; BAKER, STEPHEN MS. Nosocomial pneumonia in the critically ill: Product of aspiration or translocation? Crit Care Med 1991; 19:763 Conflict of Interest:Tonometric patents issued in my name |
|||
|
|
|||
|
Richard G Fiddian-Green, FRCS, FACS None
Send letter to journal:
|
In his reply to my eLetter Dr McIlroy points out that there was "no relationship between surrogate measures of intravascular volume status (central venous pressure and pulmonary artery diastolic pressure) and volume of intraoperative colloid" but that he did not record urine output or fluid balance in his study. Satoshi Ohki et al (1) measured blood volume, with CO-labeled haemogloblin, in their study of ICU patients having just had coronary artery bypass grafting in which no patient received blood transfusion "but each received 476 ± 96 ml albumin 4% solution, 1508 ± 160 ml lactated Ringer's solution and 1238 ± 121 ml of glucose 5% solution". The gastric intramucosal pH (pHi) was decreased at six hours after ICU admission when both the systemic hemodynamics and oxygen balance were within normal ranges and then recovered to normal at 24 h. The lowered pHi increased with an increase in blood volume (BVc), and a fall in systemic vascular resistance, despite fluid balance being negative. Furthermore the change in BVc was linearly related to the change in pHi. These investigators failed to validate their hypothesis, that reduced blood volume was a major contributor to the postoperative decrease in pHi, concluding that "the recovery of pHi between six and 24 hr after ICU admission may be a result of improved splanchnic perfusion through the increase in BVc from systemic vasodilation. They observe, however, that extracellular fluid volume increases during open-heart surgery with CPB and conclude that "negative fluid balance was a result of high urine output in the diuretic phase [and that]..the increase in BVc observed ..might be a result not only of postoperative transfusion but also of reabsorption of ECF into the vascular space". Given the magnitude of the diuresis the potential for adenine nucleotide loss immediately after cardiac surgery, and presumably lung transplant, would seem to be very real but might be restricted to those who develop a very low pHi for reperfusion injury, and hence irreversible degradation into uric acid, depends upon xanthine dehydrogenase being converted into to xanthine oxidase. Reperfusion injury, and by inference the generation of xanthine oxidase, in not encountered in gut mucosa in which the intramucosal pH has been maintained at normal levels. In the correspondence to the above study it was suggested that blood volume might be a dynamic variable in an healthy subject and that the pHi might dictate in part the size of the blood volume in patients having cardiac surgery possibly by determining the direction and magnitude of the net flux of sodium, and osmotic equivalent of water, across cell membranes. In gut mucosa these fluxes as acutely sensitive to changes in extracellular pH (2). Reperfusion of ischaemic gut mucosa would seem to be an important cause of lung injury (3). The pressing clinical question raised by McIlroy's eLetter is whether the adequacy of fluid transfusion be accurately assessed from measurements of central venous pressure, pulmonary artery diastolic pressure or even stroke volume especially in those at greatest risk of dying? If having a normal pHi is an indication of adeqacy then the answer is clearly no. 1. Satoshi Ohki, Fumio Kunimoto, Yukitaka Isa, Hiroshi Tsukagoshi, Susumu Ishikawa, Akio Ohtaki, Toru Takahashi, Tetsuya Koyano, Noboru Oriuchi, and Yasuo Morishita. Changes in gastric intramucosal pH and circulating blood volume following coronary artery bypass grafting. Can J Anesth 2000; 47: 516-521 2. Fiddian-Green RG, Silen W Mechanisms of disposal of acid and alkali in rabbit duodenum. Am J Physiol. 1975 Dec;229(6):1641-8. 3. Axon RN, Baird MS, Lang JD, Brix AE, Nielsen VG. PentaLyte decreases lung injury after aortic occlusion-reperfusion. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1982-90 Conflict of Interest:Tonometric patents issues in my name |
|||
|
|
|||
|
Richard G Fiddian-Green, FRCS, FACS None
Send letter to journal:
|
The failure to reliably assess, with conventional forms of monitoring, the volume of fluid needed in the acutely ill may be the thin edge of a very large wedge. When a house surgeon at Mary's I was told to get the Professor of Medicine to see one of our patients who had become grossly oedematous. Prof Peart had one look at the patient, made a quick calculation and declared in less than complementary terms that our patient was fluid overloaded to the degree of some 15 L or more. He instructed me to get a blood donor set from the blood bank, remove a pint of blood, spin it down, return the red cells sans the fluid, and repeat the process until normal fluid volume had been restored. I recall having done this for one pint but do not recall having done it for more or the outcome. Since that time the Michelin Man problem, seemingly the cummulative product of our failure to be able to fine tune fluid delivery with conventional forms of monitoring, has become ubiquitous in the modern surgical ICU especially in patients who have sustained multiple injuries from blunt trauma and those who have developed "septic shock". Furthermore a new syndrome, the intra-abdominal compartment syndrome, that appears to be the by-product of the current practice of incrementally increasing the volume of body water well above normal levels, has evolved. Professor Peart, a world reknowned authority on hypertension and renal disease, including the relationship between splanchnic vasodilation and hypotension and the management of acute renal failure (1,2). In offering his advice he must have been acutely aware of the risk of precipitating hypotension and acute renal failure. Have we been overloading our patients for decades? What of his recommendation? Might it have been appropriate? 1. Kooner JS, Raimbach S, Watson L, Bannister R, Peart S, Mathias CJ. Relationship between splanchnic vasodilation and postprandial hypotension in patients with primary autonomic failure. J Hypertens Suppl. 1989 Dec;7(6):S40-1. 2. W. B. Thomson, A. A. Buchanan, P. B. Doak, and W. S. Peart Peritoneal Dialysis. Br Med J. 1964 April 11; 1(5388): 932–935. Conflict of Interest:None declared |
|||
|
|
|||
|
David R McIlroy, Anesthesiologist Columbia University, College of Physicians and Surgeons, David V. Pilcher, Greg I. Snell
Send letter to journal:
|
We thank Dr Fiddian-Green for his interest in our recent paper investigating the role of anaesthesia factors in early outcomes after lung transplantation (1) and welcome his comments regarding potential alternative mechanistic explanations for our findings. However, our data did not include information on either urine output or fluid balance in the perioperative period. Furthermore we found no relationship between surrogate measures of intravascular volume status (central venous pressure and pulmonary artery diastolic pressure) and volume of intraoperative colloid. Although interesting, we believe that our data neither supports nor refutes a hypothesis of adenine nucleotide pool depletion. However, we would endorse the conclusion of Dr Fiddian-Green that the metabolic effects of varying types of fluid resuscitation are worthy of further investigation. References: 1. D. R. McIlroy, D. V. Pilcher, and G. I. Snell Does anaesthetic management affect early outcomes after lung transplant? An exploratory analysis. Br. J. Anaesth. 2009; 102: 506-514 Conflict of Interest:None declared |
|||
|
|
|||
|
Richard G Fiddian-Green, FRCS, FACS None
Send letter to journal:
|
This study (1) has shown an inverse relationship between volume of intraoperative colloid and early lung allograft function. This is consistent not only with fluid overload but also with the possibility that lung injury might also be the product of translocation (2). There is another possibility. Postoperative organ function might also be a function of the degree to which the adenine nucleotide pool were depleted during perioperative management. Seeing copious amounts of urine produced during and even after surgery makes surgeons, anaesthetists and intensivists happy but has an unappreciated potential to deplete adenine nucleotide pools if it enhances the excretion of uric acid. Indeed oliguria and particularly anuria might, because of the salvage pathways that come into play before irreversible degradation into uric acid occurs, limit and even prevent the depletion of the adenine nucleotide pools. The development of a "lactic acidosis" might also preserve adenine nucleotide pools for lactate competes successfully with uric acid for excretion by the kidneys. Ingwall, of Harvard, claims that ATP depletion is a serious biochemical abnormality for it may take as long as 300 days to replenish (4) and might never occur if significant degrees of impairment of mitochondrial oxidative phosphorylation are allowed to persist. Keeping patients dry might indeed be better than keeping patients wet perioperatively (5) especially in trauma patients. The present study adds to the weight of evidence suggesting that fluid management needs to be reviewed from a metabolic perspective. 1. D. R. McIlroy, D. V. Pilcher, and G. I. Snell Does anaesthetic management affect early outcomes after lung transplant? An exploratory analysis Br. J. Anaesth. 2009; 102: 506-514 2. Fiddian-Green RG, Baker S. Nosocomial pneumonia in the critically ill: product of aspiration or translocation? Crit Care Med. 1991 Jun;19(6):763-9. 3. Ingwall JS. ATP synthesis in the normal and failing heart. In: Heart failure, Poole-Wilson PA, Colucci WS, Massie BM, Eds, Churchill Livingston, New York, 1997 4. Ingwall JS. ATP synthesis in the normal and failing heart. In: Heart failure, Poole-Wilson PA, Colucci WS, Massie BM, Eds, Churchill Livingston, New York, 1997 5. Might saline have caused unappreciated harm in this study? Richard G Fiddian-Green (16 August 2004) eLetter re: Roy Ilan and Robert A. Fowler. Should we use albumin or saline for fluid resuscitation of critically ill patients? CMAJ 2004; 171: 232 Conflict of Interest:Tonometric patents issued in my name |
|||