" / would have everie man write what he knowes and no
BRITISH
JOURNAL
OF
VOLUME 69, No. 3
more."—MONTAIGNE
ANAESTHESIA SEPTEMBER 1992
EDITORIAL THE ROLE OF PROSTAGLANDINS IN THE CONTROL OF RENAL FUNCTION
Prostaglandins and renal haeptodynamics. T h e clin-
ically most relevant area of prostaglandin modulation of renal function is in the control of blood flow and glomerular filtration rate (GFR). Experimental studies in animals have demonstrated that prostaglandins are able to modulate vascular tone directly in the afferent arteriole and indirectly in the efferent
arteriole, via the modulation of the renin—angiotensin system [5]. In addition, they control the state of contraction of the mesangial cell [6]. Despite this, there is no good evidence that prostaglandins are essential to maintain renal function in the normal unstressed kidney. The majority of clinical studies have demonstrated that the inhibition of the cyclooxygenase system with non-steroidal antiinflammatory drugs (NSAID) does not have a clinically significant effect on renal haemodynamics in normal kidneys [7]. However, it is apparent that a small group of patients given NSAID do suffer a dramatic and severe decline in glomerular filtration rate which may be life threatening. As NSAID are highly effective analgesics and are amongst the most commonly prescribed drugs in current use, it is important to identify those patients who are likely to be at risk of adverse renal effects. Experimental evidence and clinical experience has demonstrated that it is when the renal vasoconstrictor systems have been activated that there is a particular risk from this adverse effect of NSAID. It appears that, under these conditions, the production of vasodilator prostaglandins (either prostaglandin E2 or prostacyclin) is essential to counteract the action of the vasoconstrictor(s). For example a 30 % hypotensive haemorrhage in the dog which activates both the renal sympathetic nerves and angiotensin II vasoconstrictor systems, produces a significant decrease in renal blood flow and GFR only when the cyclooxygenase enzyme has been inhibited by pretreatment with indomethacin [8]. Renal vasoconstriction is a common response to a variety of pathological conditions, and there are many mediators of this response, including other eicosanoids such as leukotrienes or the prostanoid thromboxane A2, angiotensin II, vasopressin and sympathetic nerve activation. Those conditions in which the generation of intrarenal vasoconstrictors has been implicated in the pathogenesis of the decrease in renal function and in which there is a compensatory increase in vasodilatory prostaglandins to support renal blood flow are listed in table I. It is in these conditions that die doctor should be wary of prescribing NSAID. In addition to a variety of causes of acute renal failure, it is of particular note that vasodilatory prostaglandins are essential to maintain renal function in all patients with chronic renal failure, and in these patients NSAID may be particularly hazardous [9]. An attractive alternative approach would be to develop drugs which selectively spare the renal cyclo-oxygenase and yet maintain the analgesic properties and other effects (platelet function in-
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
The term prostaglandin was coined in 1935 by von Euler in the belief that the biologically active substance found in human semen was a secretion of the prostate gland [1]. However, it is now appreciated that the cellular mechanisms responsible for the formation of prostaglandins are present in all organs in the body. Prostaglandins are part of a larger family of closely related vasoactive unsaturated fatty acids termed eicosanoids. These compounds are derived from 20-carbon polyunsaturated fatty acid precursors which are found in the cell membrane acylated to phospholipids. They are cleaved by the actions of phospholipase C and phospholipase As and oxygenated through the action of either the lipooxygenase or cyclo-oxygenase enzymes to form eicosanoids. Those compounds derived by the action of lipo-oxygenase are termed leukotrienes and those by the action of cyclo-oxygenase, prostanoids. The cyclo-oxygenase enzyme results in the formation of endoperoxides which are metabolized rapidly by other specific enzymes to a series of prostaglandins and thromboxane. The major membrane-bound precursor of the prostaglandins in mammalian cells is arachidonic acid, in which case die prostaglandins are referred to as dienoic prostaglandins (contain two double bonds) and are denoted by the subscript2, for example prostaglandin E,. Monoenoic and triehoic prostaglandins have one and three double bonds, respectively, and are derived from dihydro linoleic and eicospentanoic acid; these species are found less commonly and tend to have less biological activity. The kidney, especially the renal medulla, is one of the most active prostaglandin producing tissues. It is clear, however, that most nephron segments from the glomerulus [2] to the collecting duct [3] are capable of synthesizing prostaglandins, although the exact pattern of prostaglandin production within the kidney varies along the nephron segment according to the degree of stimulation present. In addition, renal interstitial cells may produce prostaglandins [4] and the cyclo-oxygenase enzyme has also been demonstrated in the afferent arteriole. The function of the prostaglandins produced-within the kidney has been the subject of intense study in recent years. It has now become clear that endogenous prostaglandin biosynthesis is capable of modulating many diverse renal functions.
BRITISH JOURNAL OF ANAESTHESIA
234 TABLE I. Condition! under which renal blood flow and glomerular filtration rate are supported by vasodilatory prostaglandins
hibition) of cyclo-oxygenase inhibitors. Sulindac may offer some advantages in this respect [10, 11], but this has not been a universal finding [12, 13]. A recent study of the drug ketorolac trometamol [14] suggests it does not cause the same degree of renal impairment as other NSAID when used in the treatment of postoperative pain. These findings need to be extended to other conditions in which renal vasoconstriction is balanced by the production of vasodilatory prostaglandins. Prostaglandins also control regional blood flow within the kidney, with cyclo-oxygenase inhibition preferentially decreasing medullary blood flow [15]. In addition, the intrarenal vasodilatory actions of some drugs such as frusemide may be mediated through the production of vasodilatory prostaglandins [16]. Prostaglandins and renal tubular function. There
has been much debate on whether or not the effect of prostaglandins on salt and water excretion by the kidney is a direct result of action on tubular function, or merely a result of modulation of renal blood flow. However, the identification of cyclo-oxygenase in the interstitial cells of the renal medulla and papilla and in the collecting duct has led support to the former hypothesis. Experimental evidence has demonstrated that prostaglandin E s may antagonize the effect of ADH in vivo [17] and may inhibit the reabsorption of sodium and chloride in the proximal and distal nephron and the loop of Henle [18-20]. In addition, in the dog, cyclo-oxygenase inhibition results in antidiuresis without any effect on renal haemodynamics [21]. Inhibition of cyclo-oxygenase would be expected, therefore, to result in salt and water retention. However, this effect appears to be of little clinical significance in normal individuals, but does become important when there is pre-existing hypertension or sodium depletion, when the effect of antihypertensives and diuretics are antagonized [22, 23]. Increased renal production of prostaglandins used to be considered the primary pathogenetic defect in Banter's syndrome. This syndrome is characterized
Other renal actions of prostaglandins. Renal prosta-
glandin production may also play a role in the regulation of renal hormones, including renin secretion [24] and, possibly, erythropoietin production [25]. In addition, prostaglandins may modulate release of adrenergic neurotransmitter [26]. In summary, renal prostaglandin production has the potential to influence a multitude of renal functions. How prostaglandins affect renal function appears to depend on the underlying physiological state of the subject and the kidney. In the majority of cases, generation of renal prostaglandins serves as a counterbalance to other hormonal influences and acts to maintain normal renal function in the face of disease or circulatory stress. Only in these instances does inhibition of the cyclo-oxygenase enzyme precipitate a severe decline in renal function. K. Harris Leicester REFERENCES 1. Euler US von. A depressor substance in the vesicular gland. Journal of Physiology (London) 1935; 84: 2IP. 2. Folkert VW, Yuins M, Schlondorff D. Prostaglandin synthesis linked to phosphatidylinositol turnover in isolated rat glomemli. Biochimca Biophysica Acta 1984; 794: 206-217. 3. Grenier FC, Rollins TE, Smith WL. Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture. American Journal of Physiology 1981; 241: F94-F104. 4. Zusman RM, Keiser HR. Prostaglandin biosynthesis by rabbit renomedullary interstitial cells in tissue culture. Stimulation by angiotensin I, bradykinin and arginine vasopressin. Journal of Clinical Investigation 1977; 60: 215-223. 5. Schnerman J, Briggs JP, Weber PC. Tubuloglomerular feedback, prostaglandins and angiotensin in the autoregulation of glomerular filtration rate. Kidney International 1984; 25: 53-64. 6. Scharschmidt LA, Lianos E, Dunn MJ. Arachidonate metabolites and the control of glomerular filtration. Federation Proceedings 1983; 42: 3058-3063. 7. Lifschitz MD. Renal effects of nonsteroidal antiinflammatory agents. Journal of Laboratory and Clinical Medicine 1983; 102: 313-323. 8. Henrich WL, Bcrl T, McDonald KM, Anderson RJ, Schrier RW. Angiotensin II, renal nerves, and prostaglandins in renal hemodynamics during hemorrhage. American Journal of Physiology 1978; 235: F46-F51. 9. Whelton A, Stout RL, Spilman PS, Klassen DK. Renal effects of ibuprofen, piroxicam and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison. Annals of Internal Medicine 1990; 112: 568-576. 10. Mistry CD, Lote CJ, Gokal R, Currie WJC, Vandenburg M, Mallick NP. Effects of sulindac on renal function and prostaglandin synthesis in patients with moderate chronic renal insufficiency. Clinical Science 1986; 70: 484. 11. Erikson LO, Stufelt G, Thysell H, Wollheim FA. Effects of
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
Effective circulatory volume contraction Haemorrhage Septic shock Reduced cardiac output Nephrotic syndrome Cirrhosis with ascites Anaesthesia/surgery Pre-cclampsia Sodium depletion: Diuretics Gastrointestinal losses Heat stroke Renal artery stenosis Glomerulonephritis Urinary tract obstruction Toxic injury Drugs: Cyclosprin A Gentamicin Urinary tract infection Hypercalcaemia Increasing age Chronic renal failure
by salt and potassium wasting, hypokalaemic alkalosis, juxtaglomerular hyperplasia, hyper-reninaemia and hyperaldosteronism, normal arterial pressure with a resistance to pressor agents and a defect in platelet aggregation. It may be partially corrected with the use of cyclo-oxygenase inhibitors. However, it is now apparent that the primary defect is in sodium permeability in the thick ascending limb, with the changes in prostaglandin production occurring secondary to the hypokalaemia (enhanced prostaglandin production also occurs in diuretic abuse and bulimia, which may mimic Banter's syndrome).
EDITORIAL
12. 13.
14. 15.
16.
17.
19. Fulgraff G, Meiforth A. Effects of prostaglandin E, on excretion and reabsorption of sodium and fluid in rat kidneys (micropuncture studies). Pflugers Archiv 1971; 330: 243256. 20. Stokes JB. Effect of prostaglandin E, on chloride transport across the rabbit thick ascending limb of Henli. Selective inhibition of the medullary portion. Journal of Clinical Investigation 1979; 64: 495-502. 21. Walker BR. Antidiuresis and decreased sodium excretion during cyclo-oxygenase inhibition in the conscious dog. Renal Physiology 1983; 6: 53-62. 22. Houston MC. Non-steroidal anti-inflammatory drugs and antihypertensives. American Journal of Medicine 1991; 90: 42S-47S. 23. Passmore AP, Copeland S, Johnston GD. The effects of ibuprofen and indomethacin on renal function in the presence and absence of frusemide in healthy volunteers on a restricted sodium diet. British Journal of Clinical Pharmacology 1990; 29: 311-319. 24. Vander AJ. Direct effects of prostaglandin on renal function and renin release in anesthetized dogs. American Journal of Physiology 1968; 214: 218-221. 25. Arce JM, Naughton BA, Kolks GA, Liu P, Gordon AS, Piliero SJ. The effects of prostaglandins on erythropoiesis. Prostaglandins 1984; 21: 367-377. 26. Malik K, McGiff JC. Modulation of prostaglandins of adrenergic transmission in the isolated perfused rabbit and rat kidney. Circulation Research 1975; 36: 599-609.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
18.
sulindac and naproxen on prostaglandin excretion and function in patients with impaired renal function and rheumatoid arthritis. American Journal of Medicine 1990; 89: 313-321. Harris KPG, Jenkins D, Walls J. Non-steroidal antiinflammatory drugs and cyclosporin A: A potentially serious adverse interaction. Transplantation 1988; 46: 598-599. Henrich WL, Brater DC, Campbell WB. Renal haemodynamic effects of therapeutic plasma levels of sulindac sulfide during haemorrhage. Kidney International 1986; 29: 484. Aitken HA, Burns JW, McArdle CS, Kenny GNC. Effects of ketorolac trometamol on renal function. British Journal of Anaesthesia 1992; 68: 481-485. Kirschenbaum MA, White N, Stein JH, Ferris TF. Redistribution of renal cortical blood flow during inhibition of prostaglandin synthesis. American Journal of Physiology 1974; 227:801-805. Williamson HE, Bourland WA, Marchand GR. Inhibition of furosemide increase in renal blood flow by indomethacin. Proceedings of the Society for Experimental Biology and Medidne 1975; 148: 164-166. Lum GM, Aisenberg GA, Dunn MJ, Berl T, Schrier RW, McDonald KM. In vivo effect of indomethacin to potentiate the renal medullary cyclic AMP response to vasopressin. Journal of Clinical Investigation 1977; 59: 8-13. Kinoshita Y, Romero JC, Knox F. Effect of renal interstitial infusion of arachidonic acid on proximal sodium reabsorption. American Journal of Physiology 1989; 26: F237-F242.
235
All you want - in a single anaesthesia monitor.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
AS!3~ starts where you start - with whatever anaesthesia machine you are currently using. At the same time it allmi's you to upgrade as your needs evolve.
Datex AS/3.
All you want, on a single screen Designed and tested by anaesthetists themselves, the Datex AS/3" Anaesthesia Monitor shows you all you want to know, even for the most demanding anaesthesia applications, on a single high-resolution display. It's ready to monitor the moment you are, yet fully configurable to your individual preferences.
AS/3""s modular design allows you to configure your anaesthesia workstation to your own space and patient requirements. Put the screen and controls where you can use them and see the patient at the same time. Place secondary components out of the way.
•Smart Start* single button start-up The Datex AS/3" Anaesthesia Monitor is ready for monitoring, the moment you turn it on. Direct function keys and intuitive menus keep operation straight forward and rapid, freeing you to monitor your first priority - your patient.
Alarms that inform AS/3" alerts you through an integrated system of alarms priorized for anaesthesia. Colour coding, staged audible alarms, fast problem identification and rapid alarm reset all contribute to monitoring convenience and patient safety.
The system you can build on The Datex AS/3™ Anaesthesia System grows with you as technology advances and needs change. AS/3" is modular in design - even down to the control software itself - making servicing and upgrading simply a matter of adding or replacing components.
The Datex AS/3™ Anaesthesia Monitor lets you decide what information should be displayed. And Datex AS/3' where to display it. Place Anaesthesia Monitor - easy to use, equally the display wherever you easy to upgrade. choose for optimal viewing. Add a second flat screen or slave display. Locate the vital monitoring modules near your patient on the single-cable extension frame. Leave the secondary components out of the way. AS/3 s smart, compact modules are optimized for the needs of OR monitoring. Individually, you can locate them in just about any configuration you like. Together, they combine high-capability haemodynamic and multigas monitoring in a single, fully integrated unit. Datex AS/3 - nothing less than the future of anaesthesia monitoring.
Datex safe anaesthesia care In the U.K.: S&W Vickers Ltd Ruxley Comer Sidcup Kent DA 14 5BL Tel 081 3090433 Fax 081 3090919 In Rep of Ireland: H.P.I. Ltd Kjiocklyon Industrial Estate Templeogue Dublin 16 Tel 01 943395 Fax 01 943566 Datex Division Instrumentarium Corp. P.O Box 446 SF-O0101 Helsinki Finland Tel +358 0 394 II Fax +358 0 146 3310
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
Design your own workstation
your anaesthesia workstation dictate how you work? It needn't any more. Now, you can design your anaesthesia workstation the way you really want it to work. In line with your space limitations, patient needs and hospital preferences. And with the flexibility to adapt as your needs change.
BRITISH
JOURNAL
OF
VOLUME 69, No. 3
more."—MONTAIGNE
ANAESTHESIA SEPTEMBER 1992
EDITORIAL THE ROLE OF PROSTAGLANDINS IN THE CONTROL OF RENAL FUNCTION
Prostaglandins and renal haeptodynamics. T h e clin-
ically most relevant area of prostaglandin modulation of renal function is in the control of blood flow and glomerular filtration rate (GFR). Experimental studies in animals have demonstrated that prostaglandins are able to modulate vascular tone directly in the afferent arteriole and indirectly in the efferent
arteriole, via the modulation of the renin—angiotensin system [5]. In addition, they control the state of contraction of the mesangial cell [6]. Despite this, there is no good evidence that prostaglandins are essential to maintain renal function in the normal unstressed kidney. The majority of clinical studies have demonstrated that the inhibition of the cyclooxygenase system with non-steroidal antiinflammatory drugs (NSAID) does not have a clinically significant effect on renal haemodynamics in normal kidneys [7]. However, it is apparent that a small group of patients given NSAID do suffer a dramatic and severe decline in glomerular filtration rate which may be life threatening. As NSAID are highly effective analgesics and are amongst the most commonly prescribed drugs in current use, it is important to identify those patients who are likely to be at risk of adverse renal effects. Experimental evidence and clinical experience has demonstrated that it is when the renal vasoconstrictor systems have been activated that there is a particular risk from this adverse effect of NSAID. It appears that, under these conditions, the production of vasodilator prostaglandins (either prostaglandin E2 or prostacyclin) is essential to counteract the action of the vasoconstrictor(s). For example a 30 % hypotensive haemorrhage in the dog which activates both the renal sympathetic nerves and angiotensin II vasoconstrictor systems, produces a significant decrease in renal blood flow and GFR only when the cyclooxygenase enzyme has been inhibited by pretreatment with indomethacin [8]. Renal vasoconstriction is a common response to a variety of pathological conditions, and there are many mediators of this response, including other eicosanoids such as leukotrienes or the prostanoid thromboxane A2, angiotensin II, vasopressin and sympathetic nerve activation. Those conditions in which the generation of intrarenal vasoconstrictors has been implicated in the pathogenesis of the decrease in renal function and in which there is a compensatory increase in vasodilatory prostaglandins to support renal blood flow are listed in table I. It is in these conditions that die doctor should be wary of prescribing NSAID. In addition to a variety of causes of acute renal failure, it is of particular note that vasodilatory prostaglandins are essential to maintain renal function in all patients with chronic renal failure, and in these patients NSAID may be particularly hazardous [9]. An attractive alternative approach would be to develop drugs which selectively spare the renal cyclo-oxygenase and yet maintain the analgesic properties and other effects (platelet function in-
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
The term prostaglandin was coined in 1935 by von Euler in the belief that the biologically active substance found in human semen was a secretion of the prostate gland [1]. However, it is now appreciated that the cellular mechanisms responsible for the formation of prostaglandins are present in all organs in the body. Prostaglandins are part of a larger family of closely related vasoactive unsaturated fatty acids termed eicosanoids. These compounds are derived from 20-carbon polyunsaturated fatty acid precursors which are found in the cell membrane acylated to phospholipids. They are cleaved by the actions of phospholipase C and phospholipase As and oxygenated through the action of either the lipooxygenase or cyclo-oxygenase enzymes to form eicosanoids. Those compounds derived by the action of lipo-oxygenase are termed leukotrienes and those by the action of cyclo-oxygenase, prostanoids. The cyclo-oxygenase enzyme results in the formation of endoperoxides which are metabolized rapidly by other specific enzymes to a series of prostaglandins and thromboxane. The major membrane-bound precursor of the prostaglandins in mammalian cells is arachidonic acid, in which case die prostaglandins are referred to as dienoic prostaglandins (contain two double bonds) and are denoted by the subscript2, for example prostaglandin E,. Monoenoic and triehoic prostaglandins have one and three double bonds, respectively, and are derived from dihydro linoleic and eicospentanoic acid; these species are found less commonly and tend to have less biological activity. The kidney, especially the renal medulla, is one of the most active prostaglandin producing tissues. It is clear, however, that most nephron segments from the glomerulus [2] to the collecting duct [3] are capable of synthesizing prostaglandins, although the exact pattern of prostaglandin production within the kidney varies along the nephron segment according to the degree of stimulation present. In addition, renal interstitial cells may produce prostaglandins [4] and the cyclo-oxygenase enzyme has also been demonstrated in the afferent arteriole. The function of the prostaglandins produced-within the kidney has been the subject of intense study in recent years. It has now become clear that endogenous prostaglandin biosynthesis is capable of modulating many diverse renal functions.
BRITISH JOURNAL OF ANAESTHESIA
234 TABLE I. Condition! under which renal blood flow and glomerular filtration rate are supported by vasodilatory prostaglandins
hibition) of cyclo-oxygenase inhibitors. Sulindac may offer some advantages in this respect [10, 11], but this has not been a universal finding [12, 13]. A recent study of the drug ketorolac trometamol [14] suggests it does not cause the same degree of renal impairment as other NSAID when used in the treatment of postoperative pain. These findings need to be extended to other conditions in which renal vasoconstriction is balanced by the production of vasodilatory prostaglandins. Prostaglandins also control regional blood flow within the kidney, with cyclo-oxygenase inhibition preferentially decreasing medullary blood flow [15]. In addition, the intrarenal vasodilatory actions of some drugs such as frusemide may be mediated through the production of vasodilatory prostaglandins [16]. Prostaglandins and renal tubular function. There
has been much debate on whether or not the effect of prostaglandins on salt and water excretion by the kidney is a direct result of action on tubular function, or merely a result of modulation of renal blood flow. However, the identification of cyclo-oxygenase in the interstitial cells of the renal medulla and papilla and in the collecting duct has led support to the former hypothesis. Experimental evidence has demonstrated that prostaglandin E s may antagonize the effect of ADH in vivo [17] and may inhibit the reabsorption of sodium and chloride in the proximal and distal nephron and the loop of Henle [18-20]. In addition, in the dog, cyclo-oxygenase inhibition results in antidiuresis without any effect on renal haemodynamics [21]. Inhibition of cyclo-oxygenase would be expected, therefore, to result in salt and water retention. However, this effect appears to be of little clinical significance in normal individuals, but does become important when there is pre-existing hypertension or sodium depletion, when the effect of antihypertensives and diuretics are antagonized [22, 23]. Increased renal production of prostaglandins used to be considered the primary pathogenetic defect in Banter's syndrome. This syndrome is characterized
Other renal actions of prostaglandins. Renal prosta-
glandin production may also play a role in the regulation of renal hormones, including renin secretion [24] and, possibly, erythropoietin production [25]. In addition, prostaglandins may modulate release of adrenergic neurotransmitter [26]. In summary, renal prostaglandin production has the potential to influence a multitude of renal functions. How prostaglandins affect renal function appears to depend on the underlying physiological state of the subject and the kidney. In the majority of cases, generation of renal prostaglandins serves as a counterbalance to other hormonal influences and acts to maintain normal renal function in the face of disease or circulatory stress. Only in these instances does inhibition of the cyclo-oxygenase enzyme precipitate a severe decline in renal function. K. Harris Leicester REFERENCES 1. Euler US von. A depressor substance in the vesicular gland. Journal of Physiology (London) 1935; 84: 2IP. 2. Folkert VW, Yuins M, Schlondorff D. Prostaglandin synthesis linked to phosphatidylinositol turnover in isolated rat glomemli. Biochimca Biophysica Acta 1984; 794: 206-217. 3. Grenier FC, Rollins TE, Smith WL. Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture. American Journal of Physiology 1981; 241: F94-F104. 4. Zusman RM, Keiser HR. Prostaglandin biosynthesis by rabbit renomedullary interstitial cells in tissue culture. Stimulation by angiotensin I, bradykinin and arginine vasopressin. Journal of Clinical Investigation 1977; 60: 215-223. 5. Schnerman J, Briggs JP, Weber PC. Tubuloglomerular feedback, prostaglandins and angiotensin in the autoregulation of glomerular filtration rate. Kidney International 1984; 25: 53-64. 6. Scharschmidt LA, Lianos E, Dunn MJ. Arachidonate metabolites and the control of glomerular filtration. Federation Proceedings 1983; 42: 3058-3063. 7. Lifschitz MD. Renal effects of nonsteroidal antiinflammatory agents. Journal of Laboratory and Clinical Medicine 1983; 102: 313-323. 8. Henrich WL, Bcrl T, McDonald KM, Anderson RJ, Schrier RW. Angiotensin II, renal nerves, and prostaglandins in renal hemodynamics during hemorrhage. American Journal of Physiology 1978; 235: F46-F51. 9. Whelton A, Stout RL, Spilman PS, Klassen DK. Renal effects of ibuprofen, piroxicam and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison. Annals of Internal Medicine 1990; 112: 568-576. 10. Mistry CD, Lote CJ, Gokal R, Currie WJC, Vandenburg M, Mallick NP. Effects of sulindac on renal function and prostaglandin synthesis in patients with moderate chronic renal insufficiency. Clinical Science 1986; 70: 484. 11. Erikson LO, Stufelt G, Thysell H, Wollheim FA. Effects of
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
Effective circulatory volume contraction Haemorrhage Septic shock Reduced cardiac output Nephrotic syndrome Cirrhosis with ascites Anaesthesia/surgery Pre-cclampsia Sodium depletion: Diuretics Gastrointestinal losses Heat stroke Renal artery stenosis Glomerulonephritis Urinary tract obstruction Toxic injury Drugs: Cyclosprin A Gentamicin Urinary tract infection Hypercalcaemia Increasing age Chronic renal failure
by salt and potassium wasting, hypokalaemic alkalosis, juxtaglomerular hyperplasia, hyper-reninaemia and hyperaldosteronism, normal arterial pressure with a resistance to pressor agents and a defect in platelet aggregation. It may be partially corrected with the use of cyclo-oxygenase inhibitors. However, it is now apparent that the primary defect is in sodium permeability in the thick ascending limb, with the changes in prostaglandin production occurring secondary to the hypokalaemia (enhanced prostaglandin production also occurs in diuretic abuse and bulimia, which may mimic Banter's syndrome).
EDITORIAL
12. 13.
14. 15.
16.
17.
19. Fulgraff G, Meiforth A. Effects of prostaglandin E, on excretion and reabsorption of sodium and fluid in rat kidneys (micropuncture studies). Pflugers Archiv 1971; 330: 243256. 20. Stokes JB. Effect of prostaglandin E, on chloride transport across the rabbit thick ascending limb of Henli. Selective inhibition of the medullary portion. Journal of Clinical Investigation 1979; 64: 495-502. 21. Walker BR. Antidiuresis and decreased sodium excretion during cyclo-oxygenase inhibition in the conscious dog. Renal Physiology 1983; 6: 53-62. 22. Houston MC. Non-steroidal anti-inflammatory drugs and antihypertensives. American Journal of Medicine 1991; 90: 42S-47S. 23. Passmore AP, Copeland S, Johnston GD. The effects of ibuprofen and indomethacin on renal function in the presence and absence of frusemide in healthy volunteers on a restricted sodium diet. British Journal of Clinical Pharmacology 1990; 29: 311-319. 24. Vander AJ. Direct effects of prostaglandin on renal function and renin release in anesthetized dogs. American Journal of Physiology 1968; 214: 218-221. 25. Arce JM, Naughton BA, Kolks GA, Liu P, Gordon AS, Piliero SJ. The effects of prostaglandins on erythropoiesis. Prostaglandins 1984; 21: 367-377. 26. Malik K, McGiff JC. Modulation of prostaglandins of adrenergic transmission in the isolated perfused rabbit and rat kidney. Circulation Research 1975; 36: 599-609.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
18.
sulindac and naproxen on prostaglandin excretion and function in patients with impaired renal function and rheumatoid arthritis. American Journal of Medicine 1990; 89: 313-321. Harris KPG, Jenkins D, Walls J. Non-steroidal antiinflammatory drugs and cyclosporin A: A potentially serious adverse interaction. Transplantation 1988; 46: 598-599. Henrich WL, Brater DC, Campbell WB. Renal haemodynamic effects of therapeutic plasma levels of sulindac sulfide during haemorrhage. Kidney International 1986; 29: 484. Aitken HA, Burns JW, McArdle CS, Kenny GNC. Effects of ketorolac trometamol on renal function. British Journal of Anaesthesia 1992; 68: 481-485. Kirschenbaum MA, White N, Stein JH, Ferris TF. Redistribution of renal cortical blood flow during inhibition of prostaglandin synthesis. American Journal of Physiology 1974; 227:801-805. Williamson HE, Bourland WA, Marchand GR. Inhibition of furosemide increase in renal blood flow by indomethacin. Proceedings of the Society for Experimental Biology and Medidne 1975; 148: 164-166. Lum GM, Aisenberg GA, Dunn MJ, Berl T, Schrier RW, McDonald KM. In vivo effect of indomethacin to potentiate the renal medullary cyclic AMP response to vasopressin. Journal of Clinical Investigation 1977; 59: 8-13. Kinoshita Y, Romero JC, Knox F. Effect of renal interstitial infusion of arachidonic acid on proximal sodium reabsorption. American Journal of Physiology 1989; 26: F237-F242.
235
All you want - in a single anaesthesia monitor.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
AS!3~ starts where you start - with whatever anaesthesia machine you are currently using. At the same time it allmi's you to upgrade as your needs evolve.
Datex AS/3.
All you want, on a single screen Designed and tested by anaesthetists themselves, the Datex AS/3" Anaesthesia Monitor shows you all you want to know, even for the most demanding anaesthesia applications, on a single high-resolution display. It's ready to monitor the moment you are, yet fully configurable to your individual preferences.
AS/3""s modular design allows you to configure your anaesthesia workstation to your own space and patient requirements. Put the screen and controls where you can use them and see the patient at the same time. Place secondary components out of the way.
•Smart Start* single button start-up The Datex AS/3" Anaesthesia Monitor is ready for monitoring, the moment you turn it on. Direct function keys and intuitive menus keep operation straight forward and rapid, freeing you to monitor your first priority - your patient.
Alarms that inform AS/3" alerts you through an integrated system of alarms priorized for anaesthesia. Colour coding, staged audible alarms, fast problem identification and rapid alarm reset all contribute to monitoring convenience and patient safety.
The system you can build on The Datex AS/3™ Anaesthesia System grows with you as technology advances and needs change. AS/3" is modular in design - even down to the control software itself - making servicing and upgrading simply a matter of adding or replacing components.
The Datex AS/3™ Anaesthesia Monitor lets you decide what information should be displayed. And Datex AS/3' where to display it. Place Anaesthesia Monitor - easy to use, equally the display wherever you easy to upgrade. choose for optimal viewing. Add a second flat screen or slave display. Locate the vital monitoring modules near your patient on the single-cable extension frame. Leave the secondary components out of the way. AS/3 s smart, compact modules are optimized for the needs of OR monitoring. Individually, you can locate them in just about any configuration you like. Together, they combine high-capability haemodynamic and multigas monitoring in a single, fully integrated unit. Datex AS/3 - nothing less than the future of anaesthesia monitoring.
Datex safe anaesthesia care In the U.K.: S&W Vickers Ltd Ruxley Comer Sidcup Kent DA 14 5BL Tel 081 3090433 Fax 081 3090919 In Rep of Ireland: H.P.I. Ltd Kjiocklyon Industrial Estate Templeogue Dublin 16 Tel 01 943395 Fax 01 943566 Datex Division Instrumentarium Corp. P.O Box 446 SF-O0101 Helsinki Finland Tel +358 0 394 II Fax +358 0 146 3310
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on March 13, 2015
Design your own workstation
your anaesthesia workstation dictate how you work? It needn't any more. Now, you can design your anaesthesia workstation the way you really want it to work. In line with your space limitations, patient needs and hospital preferences. And with the flexibility to adapt as your needs change.
