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119RENAL IMPLICATIONS OF INCREASED INTRA-ABDOMINAL PRESSURE:ARE THE KIDNEYS THE CANARY FOR ABDOMINAL HYPERTENSION?

Acta Clinica Belgica, 2007; 62-Supplement 1

RENAL IMPLICATIONS OF INCREASED

INTRA-ABDOMINAL PRESSURE: ARE THE KIDNEYS

THE CANARY FOR ABDOMINAL HYPERTENSION?

I. De laet1, M.L.N.G.Malbrain1, J.L. Jadoul2, P. Rogiers3, M. Sugrue4

Key words: intra-abdominal pressure, abdominal compartment syndrome, renal failure

1 ZiekenhuisNetwerk Antwerpen,

Campus Stuivenberg,Intensive Care Unit,Antwerp, Belgium;

2 ZiekenhuisNetwerk Antwerpen,Campus Stuivenberg,Department of Anesthesiology,Antwerp, Belgium;

3 ZiekenhuisNetwerk Antwerpen,Campus Stuivenberg,Intensive Care Unit,Antwerp, Belgium;

4 Trauma, Liverpool Hospital, University of New South Wales,

Sydney, Australia

Address for correspondence:Manu LNG Malbrain, M.D.WSACS PresidentICU DirectorZiekenhuisNetwerk AntwerpenCampus StuivenbergLange Beeldekensstraat 267B-2060 Antwerpen 6BelgiumTel: +32 3 217 7399Fax: + 32 3 217 7279E-mail: [email protected]

Original article OA 14

ABSTRACT

Introduction: Increased intra-abdominal pressure(IAP) or intra-abdominal hypertension (IAH) is acause of organ dysfunction in critically ill patientsand is independently associated with mortality.The kidneys seem to be especially vulnerable to

IAH induced dysfunction and renal failure is oneof the most consistently described organ dysfunc-tions associated with IAH. The aim of this paperis to review the historical background, awareness,definitions, pathophysiologic implications andtreatment options for IAP induced renal failure.

Methods: This review will focus on the availableliterature on IAH-induced renal dysfunction. AMedline and PubMed search was performed inorder to find an answer to the question What is

the impact of increased IAP on renal function in thecritically ill?. The resulting references were includedin the current review on the basis of relevance andscientific merit.

Results: Renal dysfunction in IAH is a multifacto-rial process. The mechanisms involved have not beenclarified completely. However, decreased cardiacoutput, altered renal blood flow and hormonalchanges have been implicated. Decompressionseems to have a beneficial effect on renal dysfunc-tion, although there are some conflicting data. Thismay be due to the fact that there is no consensus

on indications for decompression, both in terms ofIAP values and of timing. An overview of currentliterature is provided and some interesting leadsfor future research are suggested.

Conclusion: IAH can cause renal dysfunction.Therefore, IAP measurements should be consideredin our daily practice and preventive measures shouldbe taken to avoid (deterioration of) renal failurein patients with IAH. Decompression may have abeneficial effect in patients with established IAHand renal failure.


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120 RENAL IMPLICATIONS OF INCREASED INTRA-ABDOMINAL PRESSURE:ARE THE KIDNEYS THE CANARY FOR ABDOMINAL HYPERTENSION?


INTRODUCTION

Intra-abdominal hypertension (IAH) and ab-dominal compartment syndrome (ACS) occurcommonly in critically ill patients. They are inde-pendently associated with mortality and organdysfunction (1, 2). The kidney is especially vulner-able to the devastating effect of increased intra-abdominal pressure (IAP) due to its anatomicalposition and blood supply. Several animal and hu-man studies have provided some insights into themechanism of renal dysfunction in IAH. Some sug-gest that the adverse effects of elevated IAP on

renal function can occur at lower levels of IAP thanpreviously thought, long before development ofovert ACS. The mechanism of renal impairment inACS is not yet completely understood. However,there is evidence available that renal blood flowand/or altered hormone levels may be involved.This paper will review the historical background,awareness, definitions, pathophysiologic implica-tions and treatment options for IAP induced renalfailure.

METHODS

This review will focus on the available literatureon IAH-induced renal dysfunction. A Medline andPubMed search was performed in order to find ananswer to the question What is the impact ofincreased IAP on renal function in the critically ill?.The resulting references were included in the cur-rent review on the basis of relevance and scien-tific merit (based on the well established level ofevidence grading).

HISTORICAL BACKGROUND

As was nicely pointed out recently by Schein,the effects of elevated IAP have been known since1863, when Marey of Paris highlighted that theeffects that respiration produces on the thorax arethe inverse of those present in the abdomen (3).In 1876, Wendt first described the association of

IAH and renal dysfunction, he noted that the

higher the IAP the less the production of urine (4).In 1911 Emerson wrote in his overview the follow-ing opening testament that may be true even today(5): the standard text-books of obstetrics, gynae-cology and surgery treat of the matter so rarely,and when it is mentioned so inaccurately, that noinformation is to be had from them Most of thetextbooks of physiology fail to mention intra-ab-dominal pressure at all. Emerson conducted nu-merous experiments in dogs showing that thecontraction of the diaphragm is the chief factor inthe rise of IAP during inspiration, that elevated IAP

increases systemic vascular resistance, that exces-sive IAP can cause death from cardiac failure evenbefore asphyxia develops: pressures as high as 45cmH2O will kill a small animal. He concluded thatthe distension of the abdomen with gas or fluidresults in cardiac compromise due to an overload-ing of the resistance in the splanchnic area andthat removal of ascitic fluid results in relief of thelabouring heart.

Thoringthon and Schmidt studied urinary outputand blood pressure changes in experimental ascitesin 1923 (6). Thus we see that almost 100 years agoample evidence existed concerning the adversephysiological effects of increased IAP on cardiac,respiratory and renal function. After an era withonly scattered attempts to shed new light on theimpact of increased IAP on renal function Bradleyand Bradley showed in their landmark paper in 1947a decreased glomerular filtration rate and renalplasma flow in 17 human volunteers with increasedIAP (7). In their study on the impact of G-suits theystated that It is well established that increasedintra-abdominal pressure alters renal function.

They also found that glomerular filtration rate(GFR) and renal plasma flow decreased to 25% ofbaseline with a 20 mmHg increase in IAP. How-ever, some landmark papers do exist. Several otherauthors later commented on the association of IAHand renal dysfunction (8-10).

In 1970 and 1972 Shenasky and Gillenwatershowed how increased IAP by counterpression (e.g.MAST suit) depresses cardiac and renal function (11,12). Early experience with laparoscopy led to the


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recognition of the adverse effects of pneumoperi-

toneum associated increase in IAP. The early 1980sproduced a few key studies: Kashtan rediscoveredthe hemodynamic effects of IAH (13) while Harman(9) and Richards (14) demonstrated the adverseeffects of increased IAP on renal function. Harmanstated The impairment in renal function producedby increased intra-abdominal pressure is a localphenomenon caused by direct renal compressionand is not related to cardiac output. They alsoshowed that the renal alterations could be reversedwith abdominal decompression. Le Roith studiedthe effects of increased IAP on plasma levels of

antidiuretic hormone (15). It was however the paperby Kron, Harman and Nolan that was considered bymany as the landmark paper showing that IAP couldbe used as a criterion to guide decompression (16).Kron stated If intra-abdominal pressure rises above25 mmHg in the early postoperative period and isassociated with oliguria and normal blood pressureand cardiac index, the patient should undergo re-exploration and decompression of the abdomenand an acute elevation of intra-abdominal pressurein the early postoperative period causes a markedimpairment of renal function independent of bloodpressure or cardiac output. Afterwards Smith re-ported reversal of postoperative anuria by decom-pressive laparotomy (17). Jacques also reportedimprovement in renal function after evacuation of

retroperitoneal hematoma (18) while Cullen re-

ported also that surgical decompression reversedrenal compromise in critically ill patients with in-creased IAP (19).

The term ACS however was first used by Fietsamet al. in the late 1980s to describe the patho-physiologic alterations resulting from IAH second-ary to aortic aneurysm surgery. They wrote: in fourpatients with ruptured abdominal aortic aneurysmsincreased IAP developed after repair. It was mani-fested by increased ventilatory pressure, increasedcentral venous pressure, and decreased urinaryoutput. This set of findings constitutes an abdom-

inal compartment syndrome caused by massiveinterstitial and retroperitoneal swelling four pa-tients received more than 25 litres of fluid resus-citation Opening the abdominal incision wasassociated with dramatic improvements (20).Hence the first definition of ACS was finally coined.Savino studied the effects of paracentesis in cir-rhotics with an IAP above 25 cmH20 (21). Paracen-tesis decreased IAP from 33 to 19 cmH20. Thisresulted in a significant decreases in total periph-eral resistance, serum creatinine, BUN, and a sig-nificant increase in cardiac output (CO), left andright ventricular stroke work, creatinine clearance,and osmolar clearance. Figure 1 shows the histori-cal IAP/IAH/ACS timeline in relation to renal im-plications.

1863: Marey describesPhysiology of IAP

1873: Wendt describesRenal impact of IAP

1875: Oderbrecht reportsBladder IAP measurement

1911: Emerson studiesIAH induced cardio-Pulmonary failure

1948: Gross introducesStaged abdominal repair

1989: Fietsam coinsTerm ACS

1984: Kron reports use ofBladder pressure asMortality predictor

1951: Baggot suggestsUse of open abdomen

1976: Richardson studiesCardiorespiratory impact of IAH

1983: Richards - DLimproves renal function

2002: FirstWCACS

2004: Foundation WorldSociety of Abdominal

Compartment Syndrome

1947: Bradley showesDecreased GFR

1850 20001900 1950

1923: Thorington studiesEffect of IAH on urine output

1972: Shenasky - MASTSuppresses renal function

1982: Harman shows negativeEffects of IAH on renal function

1982: Le Roith - IAHIncreases plasma ADH

1988: Jacques RP hematomaevacuation improves RF

1989: CullenDL improves RF

2004: secondWCACS

2007: thirdWCACS

1995: Sugrue IAH isindependent predictor for RF

2003: Biancofiore IAHIs correlated with RF

2006: Malbrain publishesWSACS Consensus

Definitions

ACS: abdominal compartment syndromeADH: anti-diuretic hormoneDL: decompressive laparotomyGFR: glomerular filtration rateIAH: intraabdominal hypertensionIAP: intraabdominal pressure

Figure 1. The historical timeline with regard to renal effects related to IAP, IAH and ACS (see text for explanation

MAST: military anti-shock trousersRF: renal failureRP: retroperitonealWCACS: World Congress on Abdominal Compartment SyndromeWSACS: World Society on Abdominal Compartment Syndrome (www.wsacs.org)


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(25, 26). They found an incidence of IAH (definedas an IAP > 25 mmHg) of 31.5%. Renal impairmentwas observed in 32% of patients with IAH. Thisstudy demonstrated a dose dependent associa-tion between IAH and renal dysfunction. Said inother words, the higher the IAP, the more pro-nounced the renal dysfunction. A forward stepwiselogistic regression analysis showed that renal im-pairment was significantly and independently cor-related with intra-operative blood transfusion ofmore than 15 units, respiratory failure and IAH. Theauthors commented that fluid loading failed toprevent the occurrence of renal failure, but did helpto limit its severity. There are limitations to this

study: IAP was measured by the transvesical tech-nique with an instillation volume of 100mL, whichhas been shown to lead to overestimation of IAP(27-30), and acute renal failure, as in the previousstudies mentioned, was defined as an on-off phe-nomenon. The current consensus definitions advo-cate the instillation of bladder priming volumesbelow 25ml (23). Nevertheless, these and otherstudies demonstrate a strong and consistent cor-relation between IAH and renal failure. The precise

Table 1

Renal effects related to IAP

Renal parenchymal compression

Renal perfusion pressure

Filtration gradient

Renal arterial blood flow

Renal venous blood flow

Renal vein compression

Renal venous (back) pressure

Tubular dysfunction

Glomerular perfusion

Glomerular filtration rate

Diuresis (oliguria to anuria)

Prerenal azotemia*

Urine sodium and chlorine

Renal vascular resistanceCorticomedullar shunting in renal plasma flow

Effective renal plasma flow

Compression ureters

Anti-diuretic hormone

Renin, angiotensin aldosterone

Sympathic nervous system stimulation

Arterial vasoconstriction

CLINICAL IMPORTANCE OF THE RELATIONSHIP

BETWEEN IAH AND RENAL DYSFUNCTION

Although renal impairment is one of the earliestand most consistently described findings in IAH,correct interpretation of the available evidence ishampered by the fact that both IAH and renaldysfunction were, until recently, poorly defined,which limits comparability between different pa-pers. Table 1 lists the effects of IAH on renal func-tion.

The first prospective clinical study was publishedby Sugrue et al in 1995 (22). They found that IAH

(defined as an on-off phenomenon with a cut-offvalue of 20mmHg) was common in 88 patientswho are admitted to the ICU after abdominal sur-gery (33%) and was associated with renal dysfunc-tion (odds ration 12.4 (3.8-41.7)), oliguria anddeath (odds ratio 11.2 (2.8-47.9)). In the case ofco-existing organ failure, the threshold of 20 mmHgused in this study would be defined as ACS accord-ing to the latest published consensus definitionsof the World Society on Abdominal CompartmentSyndrome (WSACS) (23). The same group laterpublished a larger and more elaborate paper (ad-justing for other risk factors) concerning renalfunction in 263 patients admitted to the ICU afterabdominal surgery (24). IAH occurred in 40.7% ofpatients (using a cut-off value of 18mmHg) and itwas an independent predictor for renal failure.Renal failure developed in 32.7% of patients withIAH versus 14.1% in those with normal IAP (definedas a postoperative serum creatinine level greaterthan 1.47mg/dL or an increase in serum creatininelevel >1.13mg/dL).

Using multivariate analysis, the authors found

that renal impairment was significantly and inde-pendently associated with 4 factors: hypotension,sepsis, age over 60 years and increased IAP.

The mean lag time between onset of IAH andrenal impairment was 2.7 6.5 days. IAH occurredmost frequently in the first two days after sur-gery.

Another recent paper by Biancofiore et al stud-ied the incidence of IAH and renal dysfunction in34 patients after orthotopic liver transplantation


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nature and course of the association have to be

studied further as new consensus definitions forboth IAH and renal dysfunction are being agreedupon (23, 31). Several mechanisms have been pro-posed to link IAH and renal failure, most of themrelating to the kidney blood supply (32, 33). Themost frequently mentioned mechanisms are de-creased CO, decreased renal perfusion pressure(RPP), increased renal venous pressure (RVP), de-creased glomerular filtration gradient, decreasedmicrocirculatory flow and direct compression ofthe renal cortex. Several animal and human studieshave focused on this topic

THE INFLUENCE OF IAH ON RENAL BLOOD

FLOW

Many organs are capable of maintaining rela-tively constant blood flow over a wide range ofperfusion pressures. The efficiency of this autoreg-ulation differs from organ to organ and is the mostefficient in the brain and kidneys. However virtu-ally all organs exhibit this sort of autoregulation. Inmost cases blood flow is believed to be preservedwithin the mean pressure range of 70 to 160 mmHg.For the kidney autoregulation has also been de-scribed in relation to the constant glomerular filtra-tion rate (GFR) in response to variations in perfusionpressure. Adapting the renal vascular resistance ofthe pre- and post-glomerular arterioles vasculatureis the key-factor for autoregulation mediated bymechanisms intrinsic to the kidneys, which mayreside in the vascular wall. Although decreased COcertainly has the potential to impair renal function,it is probably not the most contributing factor, since

it has been shown that correction of the cardiacoutput by volume loading is not successful in pre-venting acute renal failure in IAH (9, 19, 26, 34-37).Other studies showed a beneficial effect on renalfunction with volume expansion (38).

Another hypothesis states that renal perfusionpressure is decreased in IAH. In analogy to ab-dominal perfusion pressure (APP), renal perfusionpressure (RPP) is defined as mean arterial pressure(MAP) minus IAP. However, renal dysfunction can-

not be prevented by increasing MAP and thus RPP

(34, 37). Ulyatt suggested that filtration gradient(FG) is a more important factor in explaining renalfailure associated with IAH (39). The FG is the me-chanical force across the glomerulus and is equalto the difference between glomerular filtrationpressure and the proximal tubular pressure. In thisformula, the glomerular filtration pressure is equalto RPP and thus to MAP IAP. In the presence ofIAH, proximal tubular pressure will be close to IAP.The FG can therefore be calculated as FG = MAP (2x IAP). This explains why the kidney seems tobe more vulnerable to IAH than other surrounding

organs and is probably one of the key factors in thedevelopment of IAH-induced renal failure (40, 41).Pressure on the ureter causing postrenal renal fail-ure have been excluded as a contributing factorsince placement of ureteral stents does not resolverenal impairment (9).

Several studies have also been performed on theinfluence of IAH on renal venous blood flow. Dotyet al published a study in 1999 where renal venouspressure (RVP) was increased by banding in pigs(42). The elevation in RVP caused a significant de-crease in renal blood flow (RBF) compared withcontrols, whereas CO and MAP remained un-changed. This also caused a decrease in inulin clear-ance. The RBF and inulin clearance returned tobaseline after normalisation of RVP. Although theexperimental setup was not an IAH model, thesefindings show a clear association between RVP andrenal dysfunction. It is assumed that RVP is equalto IAP, and thus increased, in IAH.

The same group also performed a later study onthe influence of increased renal parenchymal pres-sure on renal function (34). They found that direct

parenchymal compression had no effect on CO,MAP, RBF or inulin clearance. Also, supranormalelevation of RPP made no difference. The authorscomment that the experimental setup does notreflect the clinical situation of IAH, in which directcompression of the parenchyma is a secondaryinsult on an injured kidney in stead of a purelymechanical effect on a healthy organ. In contrast,Stone et al subjected rhesus monkey kidneys toischemia by aortic cross clamping and decapsu-


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lated one kidney (43). After 8-20 days, the capsu-

lated kidney had significantly less renal functioncompared to the decapsulated contralateral kidney.This lead to the term local renal (allograft) com-partment syndrome and suggests that parenchy-mal compression may be an important contributorto renal failure when it is applied in an injured kid-ney (which may better reflect clinical IAH) (44-47).Doty et al conclude after both their studies thatincreased RVP, leading to decreased venous returnand shunting from blood from the renal cortex tothe medulla, is probably a more significant factorthan parenchymal compression in the association

between IAH and renal dysfunction (34, 42).All previously mentioned studies have been piv-

otal in unravelling the underlying mechanisms of theassociation between IAH and renal failure. However,the kidney vasculature is not readily accessible formonitoring in a clinical setting, which is a majorlimitation in any attempt to guide treatment. A re-cent, very well designed study was performed byKirkpatrick et al, describing the relationship betweenIAH and intrarenal blood flow, as measured by renalarcuate artery resistive index (RI) on Doppler ultra-sound, in pigs (48). The authors found a linear cor-relation between RI and IAP. With increasing levelsof IAH, peak systolic blood flow velocity increasedand end-diastolic flow velocity decreased linearly.The use of RI has been clinically validated in a numberof other renal diseases (49), but not in the setting ofIAH, except in one study (50). In Kirkpatricks ex-perimental setup, IAH was induced by instilling salineinto the peritoneal cavity which facilitated sono-graphic evaluation of the pig kidneys. It is likely thatrenal Doppler ultrasound will be more difficult in theclinical setting of ICU patients. However, in spite of

the limitations of this study, bedside RI measurementmight become a reliable tool to guide treatment ofIAH in the future after clinical validation.

HORMONAL CHANGES IN IAH INDUCED

RENAL DYSFUNCTION

Several hormones have been implicated in renalfunction changes in IAH. Le Roith et al describedincreased antidiuretic hormone (ADH) levels associ-

ated with IAH in dogs (15). Increased ADH levels

were also described by Viinamki during laparoscopy(51). This finding was confirmed recently by Haze-broek et al who found evidence of increased ADHsecretion during laparoscopic donor nephrectomycompared to open donor nephrectomy (52). ADHlevels remained significantly increased 30 minutesafter desufflation and returned to normal valuesafter 24 hours, although they were still higher thanpreoperative levels and also higher than the levelsin the open nephrectomy group. Interestingly, therewas no difference between transplant kidney func-tion or diuresis in both groups after transplantation.

Also, diuresis during the procedure was not differentbetween the groups. The exact mechanism for in-creased ADH levels in IAH is not completely under-stood, although it may be related to decreased ef-fective circulating volume, which is a major triggerfor ADH release. The trigger for ADH release isplasma osmolality, to a much lesser extent de-creased intravascular pressure plays a role. IncreasedADH secretion induces renal water reabsorption andincreases plasma volume. However, the clinical sig-nificance of these effects in IAH is unknown.

A second hormonal change observed in IAH isactivation of the renin-angiotensin-aldosterone(RAA) system. Decreased CO and reduced RBF as-sociated with IAH cause activation of the RAAsystem. Elevated renal pressures (both venous andparenchymal) reduce glomerular filtration, decreas-ing the sodium delivery to the macula densa andthus triggering renin release (38, 53-56). The result-ant aldosterone secretion leads to sodium andwater retention. Angiotensin II, which is a potentvasoconstrictor, is released, leading to further re-duced RBF and GFR. Increased RVP is probably the

most important contributing factor in this mecha-nism as was shown by Doty et al (34, 42).

Increased levels of atrial natriuretic peptide (ANP)and circulating catecholamines have also been de-scribed in IAH (57). However other studies showed noincrease in ANP during laparoscopy and speculated thatthe low filling pressures correlated with the low ANPlevel because of diminished venous return (58). In somestudies endothelin came forward as a possible auto-crine/paracrine mechanism which decreases RBF enGFR by constricting preglomerular vessels (59, 60).


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All these hormonal changes may contribute to IAH

induced renal dysfunction due to their effect on au-toregulation of the renal blood flow. However, theexact mechanism of action is not yet completely un-derstood.

THE EFFECT OF ABDOMINAL DECOMPRESSION

ON RENAL FUNCTION IN IAH

Although few of the previously mentioned stud-ies were specifically designed to look at the influ-ence of abdominal decompression on renal func-

tion, some of them contain data on this subject. Inthe first study by Sugrue et al (22) two patientsunderwent decompressive laparotomy (DL). Oneof them had no renal dysfunction at the time ofDL. The other patient was admitted for severe acutepancreatitis and developed IAH with anuria. The DLwas followed by brisk diuresis in the first 12h hoursafter surgery, but this effect was not maintained,the patient went on to require renal replacementtherapy and survived after a long hospital course.No data are provided concerning the evolution ofIAP after DL or the association with the relapse ofkidney dysfunction.

Cullen and coworkers evaluated six patients withIAH and found that DL improved renal function(19). Fietsam et al and Platell et al also recommendDL in patients with renal dysfunction and IAH (8,20). However, IAP measurement standards havechanged dramatically since these older studies havebeen published and their findings need to be inter-preted with caution today.

In an interesting and rare prospective studiesSugrue et al analysed outcomes in 49 consecutive

patients with IAH that underwent temporary ab-

dominal closure (TAC) (61). The study showed,surprisingly, no statistically significant improve-ment of renal function after DL, although 10 pa-tients exhibited brisk diuresis. Therefore, it is un-likely that abdominal decompression alone willreverse the renal sequelae of excessive IAP onceestablished. As a possible mechanism, acute tubu-lar necrosis secondary to local renal compartmentsyndrome is suggested, which takes longer to re-cuperate. A possible explanation for the contradict-ing results may lie in the timing of decompression.If performed too late acute tubular necrosis may

already have established, and you are set for 2weeks or more. In the above mentioned study,patients responding following TAC, in terms of briskdiuresis had a significantly lower post-TAC IAP,suggesting better decompression. However theexact timing of the TAC with regard to the evolutionof IAH was not mentioned.

Reddy stated in a review article on renal failurethat postoperative acute renal failure preventablerather than a treatable and he suggested someprobable mechanisms of renal ischemia from in-creased IAP (62). Reddy has to be congratulatedbecause he was the first to introduce IAP into areview article on acute postoperative renal failure,making nephrologists aware of the syndrome ofACS.

A exhaustive review of the effect of DL, sum-marizing all relevant data on the subject, was pub-lished by De Waele et al recently (63). The resultsof the effect of DL on IAP and urine output fromthe different studies are summarized in Figure 2.Interestingly, two of the larger studies (61, 64)

15,8

35,3

0

10

20

30

40

50

IAP before DL IAP after DL

55,0

175,7

0

50

100

150

200

250

300

UO before DL UO after DL

Figure 2.The IAP decreased from 35.38.4 to15.84.9 mmHg (p


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showed no effect of DL on diuresis, while most of

the smaller series (8, 19, 65-70) did find increaseddiuresis after DL, but due to the small patient num-bers, these results usually did not reach statisticalsignificance.

IF THE KIDNEY FAILS: WHAT IS THE BEST

CHOICE FOR RENAL REPLACEMENT THERAPY

DURING ACS?

First of all, the institution of renal replacementtherapy offers an ideal opportunity to control

fluid balance (provided the patient tolerates ultra-filtration from a haemodynamic point of view),which can otherwise be a problem in critically illpatients with oliguria secondary to acute renalfailure, and RRT may in itself be a good treatmentoption for IAH. A few studies have shown the ben-eficial effects of continuous venovenous hemofil-tration with aggressive ultrafiltration on IAP (71,72).

However, in terms of outcome the best RRTmodality is still a matter of debate. The use ofperitoneal dialysis in patients with primary ACS is

contra-indicated for obvious reasons (such as intra-abdominal sepsis, trauma or deterioration of res-piratory mechanics)(73) but data are lackingconcerning secondary ACS. One paper from 1989described lower peritoneal mass transfer coefficientvalues in 8 (not critically ill) patients with poly-cystic kidneys and IAH compared to controls, whilethe ultrafiltration capacity was preserved (74). HighIAP has recently also been identified as a risk factorfor abdominal wall complications in patients onchronic ambulatory peritoneal dialysis (CAPD) (73).

Besides IAP, advanced age, polycystic kidney diseaseand high BMI were also independent risk factorsfor these complications. The authors suggest thatautomated CAPD with low daytime fill volume andpressures should be considered in all patients atrisk for hernias and/or leaks (73). Others alsonoted a strong correlation between BMI and IAP inchildren on PD (75, 76). This correlation gives abetter understanding of the interindividual variabil-ity of the above described unique relationshipbetween IAP and intraperitoneal volume. To our

knowledge, there are no reports on critically ill

patients with IAH and peritoneal dialysis, which isnot surprising since few centres use peritonealdialysis as a first choice in unstable sepsis ortrauma patients. As for the choice between inter-mittent (IHD) and continuous RRT (CRRT), thedebate goes on. There are certainly conflicting re-sults to be found in the literature. The recent meta-analyses, and all the prospective randomized stud-ies failed to demonstrate a survival benefit in favourfor CRRT (77-83). In fact some studies showedhigher mortality in CRRT-treated patients. The mostrecent study by Vinsonneau and the largest one so

far, found that IRRT was well tolerated, but therewere no more therapy switches in the IRRT groupcompared to the CRRT group (79). It is our experi-ence that intermittent RRT will not be toleratedhaemodynamically in many unstable ACS patients.Therefore, CRRT with a low blood flow (CVVH,SLEDD or hybrid technique) is the treatment ofchoice in our institution. In trauma patients, hypo-thermia, acidosis and coagulopathy are often re-ferred to as the deadly triad leading to ongoingbleeding and ACS. Because patients with ACS oftenneed to undergo several surgical or percutaneous

procedures, have low platelets and coagulationdisturbances, citrate seems the anticoagulation ofchoice during RRT in these patients (84).

WHERE DO WE GO FROM HERE?

Although renal dysfunction is one of the mostfrequently and most consistently described organdysfunctions related to IAH, there are relatively few

clinically useful data that offer guidance for treat-ment. Some of the older studies have major limita-tions:- different threshold levels for IAP are used for the

definition of IAH- the instillation volumes used for bladder pressure

measurement are variable and sometimes unaccept-ably high

- definitions for renal dysfunction differ betweenstudies

- for both IAH and renal dysfunction, non-physiologicon-off definitions are used


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Where IAH is concerned, a consensus has been

reached on reliable IAP measurement (although thisarea of research is likely to undergo some morechanges in the near future) and graded definitionsfor IAH have been agreed upon (23, 85). As for renaldysfunction, the Acute Dialysis Quality InitiativeGroup has published consensus definitions on AcuteKidney Injury (AKI) according to the RIFLE criteria(31), which also allow for a graded classification.All RIFLE criteria have been independently associ-ated with mortality in a linear fashion, which sug-gests that they reflect, indeed, increasing levels ofseverity of renal dysfunction (86). These recent

developments allow for new large trials to betterdefine the causal or temporal association betweenIAH and AKI and will offer insights into mechanismsand indications for treatment. Future studies how-ever will have to look at specific scoring systemsto predict outcome related to acute renal failurelike the Liano, SHARF, RIFLE class (31, 87-90), andIAH, like the definition of gastro-intestinal failure(91) or a new score combining both

It has been suggested that early treatment maybe a key factor in survival after DL for ACS, but theconsiderable morbidity associated with open abdo-men treatment causes most clinicians to be reluc-tant in performing DL, especially at moderatelevels of IAP. In fact, DL can probably be safelyavoided in patients with high IAP without organdysfunction and, in contrast, can probably improveoutcome in patients with moderate levels of IAPwith organ dysfunction (although there are nodefinitive reliable data on this subject). Monitoringof subtle forms of organ dysfunction is thereforeof the utmost clinical importance in patients withIAH, especially the kidney, since this organ is very

easy to monitor and seems to be most vulnerableto the detrimental effects of IAH and may serve asa sentinel or the canary for the other organs in-volved. Renal Doppler ultrasound, as described byKirkpatrick et al, might provide an easy bedside toolfor early detection of kidney injury in the future,provided it can be clinically validated (48).

It is clear that further experimental and clinicalresearch is necessary to clarify the mechanismsinvolved in the development of renal failure during

IAH, to identify early markers of kidney dysfunction,

to link kidney dysfunction to outcome measuresand finally to guide appropriate treatment.

CONCLUSION

The kidney is especially vulnerable to the del-eterious effect of IAH on organ function. The un-derlying mechanisms are multifactorial andmostly related to changes in the very complexregulation of RBF. Hormonal changes may have anadditional impact on these changes and may impair

renal function further. Decompression may have abeneficial effect on organ function although find-ings are conflicting on this issue. So, a lot of mayin our conclusion means that many aspects of thecomplex association between IAH and renal failureremain unclear today.

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