WINTER 2011 | VOLUME 18 | NUMBER 4INTERNATIONAL JOURNAL OFINTENSIVE CARE Estimating unmeasured ions in extracellular fluid...
The NEW State of the Art ICU Bed:                                                  ®    InTouch      A Revolution in Inten...
CONTENTS WINTER 2011INTERNATIONAL JOURNAL OFINTENSIVE CARE                                           COVER PHOTOGRAPHEdito...
COMMENTAntibiotics in patients withseptic shock: are we using the                                                         ...
COMMENT                                                                                                                   ...
Setting a new standard for performance, safety and simplicityThe Arctic Sun 5000 brings precision Targeted Temperature Man...
CLINICAL NEWS From the cutting edge of research                                              Interactive video games aid  ...
INDUSTRY NEWS An update on recent industry initiatives Value of closed loop ventilation recognised by major award The winn...
REVIEWSurgical and intensive care strategiesto prevent renal failure                                Acute kidney injury (A...
STRATEGIES TO PREVENT RENAL FAILUREPREVENTIVE STRATEGIES                                            Haemodynamic optimisat...
STRATEGIES TO PREVENT RENAL FAILURE Table 1. Subgroup analyses of pooled odds ratios of renal injury in perioperative haem...
STRATEGIES TO PREVENT RENAL FAILURE Table 2. Primary pathogenetic mechanisms, specific clinical features and risk factors, ...
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
INTL Journal of Intensive Care Winter 2011
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INTL Journal of Intensive Care Winter 2011

  1. 1. WINTER 2011 | VOLUME 18 | NUMBER 4INTERNATIONAL JOURNAL OFINTENSIVE CARE Estimating unmeasured ions in extracellular fluidCurrent surgical The correct Role of novelstrategies to antibiotic doses biomarkers in acuteprevent renal failure for septic shock kidney injury
  2. 2. The NEW State of the Art ICU Bed: ® InTouch A Revolution in Intensive Care! Essential Needs Flat Deck Open Architecture, ease of decontamination Central braking system 30 HOB automatic positioning Full battery back-up Simplified Care Pre-set functions Clinical best practices TM BackSmart Built-in scale, records up to 50 days of patient weight history Exceptional Outcomes Semi-integrated therapy surface, allowing support surface to be changed as therapy dictates TM Essential Needs. Sound Therapy Simplified Care. Clinical translations Exceptional Outcomes. Upgradeability, ensuring that the InTouch bed is capable of evolving as technology and clinical practices do Contact your Stryker sales representative or visit us at www.stryker.euThis document is intended solely for the use of healthcare professionals. The information presented is intended to demonstrate the breadth of Strykerproduct offerings. A surgeon must always refer to the package insert, product label and/or instructions for use before using any Stryker product. CEpending. Stryker and iSuites are registered trademarks of Stryker Corporation.
  3. 3. CONTENTS WINTER 2011INTERNATIONAL JOURNAL OFINTENSIVE CARE COVER PHOTOGRAPHEditor Dr J Denis EdwardsSub Editor Catherine Booth Blood sample being pipetted into a sampleArt Editor Bettina Brüx bottle. Blood samples are used to evaluateIllustrator Marion TaskerAdvertisement Manager Robert Sloan oxygen levels and search for contaminatingEditorial Director Guy Wallis organisms and toxins in the blood. DuringEditorial Advisory Board critical illness, anionic species may leak fromProfessor Rinaldo Bellomo, Melbourne, Australia the intracellular environment to theDr Martina Brückmann, Mannheim, Germany extracellular fluid.Professor Pierre Carli, Paris, FranceDr Daniel De Backer, Brussels, BelgiumProfessor Guillermo Gutierrez, Washington DC, USADr Klaus Hankeln, Bremen, GermanyProfessor Hiroyuki Hirasawa, Chiba, JapanProfessor Claus-Georg Krenn, Vienna, Austria © Tek Image/Science Photo LibraryProfessor H Matsuda, Tokyo, JapanProfessor Paolo Pelosi, Varese, ItalyProfessor Azriel Perel, Tel Aviv, IsraelDr Kees Polderman, Amsterdam, The NetherlandsDr Jerome Pugin, Geneva, Switzerland REVIEWProfessor Konrad Reinhart, Jena, Germany Surgical and intensive care strategies to prevent renal failureDr Thomas Stewart, Toronto, Canada Acute kidney injury (AKI) refers to a sudden decline in kidney function causing disturbances in fluid, electrolyte,Dr Robert Tasker, Cambridge, UK and acid–base balance. Its occurrence in surgical and critically ill patients is common and it is associated withDr Antonio Torres, Barcelona, Spain a substantial increase in morbidity and mortality. In this review, N Brienza, MT Giglio and L Dalfino discuss theProfessor Jean-Louis Vincent, Brussels, Belgium epidemiology and prevention of AKI. Currently, excellent supportive care and avoidance of clinical conditionsDr Julia Wendon, London, UKDr Duncan Wyncoll, London, UK known to cause or worsen AKI remain the cornerstones of management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100Publishing Director Ashley Wallis COVER FEATURE Significance and estimation of unmeasured ions in extracellular fluid – a brief reviewThe International Journal of Intensive Care is During critical illness, anionic species may leak from the intracellular environment to the extracellular fluid.indexed in EMBASE/Excerpta Medica and in theCumulative Index to Nursing and Allied Health While these ions may not directly contribute to mortality, they do reflect underlying pathology and their ultimateLiterature (CINAHL). It is published quarterly and disappearance from the extracellular fluid is associated with a return to health. In this review, CM Anstey focusescirculated on a controlled basis to practitioners on the physiological rationale behind measurements in the extracellular fluid and on the shortfalls of the currentwho specialise in critical and emergency care, models for detecting unmeasured ions. A new parameter is introduced. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109coronary and neonatal care. All others are invitedto subscribe. Europe Overseas REVIEWIndividuals: GBP 50 (€ 60) GBP 65 (USD100) The diagnostic role of novel biomarkers in acute kidney injury in critically ill patientsInstitutions: GBP105 (€130) GBP135 (USD210) Acute kidney injury (AKI) is a common and serious condition, in particular in critically ill patients. In this review, N Lameire first discusses the drawbacks of serum creatinine and oliguria in the early diagnosis of AKI, and thenAdvertising Department reviews novel biomarkers – specifically serum cystatin C and plasma and urine neutrophil gelatinase-associatedTel/Fax: +44 (0)20 8882 7199E-mail: r.sloan@greycoatpublishing.co.uk lipocalin – that may allow the early detection, risk stratification and prognostication of patients with AKI. . . . . . . . . . 118Printed by Stones the Printers, Banbury,Oxfordshire, UK.Published by Greycoat Publishing Ltd, REGULARS148 Buckingham Palace Road, London SW1W 9TR, UK. Comment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93Tel: +44 (0)20 7730 7995. Fax: +44 (0)20 7730 3884.E-mail: mail@greycoatpublishing.co.uk Clinical news . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .96www.greycoatpublishing.co.uk Industry news . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98© Greycoat Publishing Ltd, 2011. Instructions to authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108All rights reserved. No part of this publication may Product news . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122be reproduced, stored in a retrieval system ortransmitted in any form or by any other means,electronic, mechanical, photocopying, recording,or otherwise, without prior permission, in writingfrom the publisher.ISSN 1350–2794The publishers, editor and editorial board wish tomake it clear that the data, opinions andstatements appearing in the articles herein arethose of the contributor(s) concerned; suchopinions are not necessarily shared by the editoror the editorial board. Accordingly, the publishers,editor and editorial board and their respectiveemployees, officers and agents accept no liabilityfor the consequences of any such inaccurate ormisleading data, opinions or statements.
  4. 4. COMMENTAntibiotics in patients withseptic shock: are we using the Fabio Taccone MDright doses? strated that β-lactams have a slow continuous killS epsis is one of the most common reasons for required for difficult-to-treat pathogens such as admission to an intensive care unit (ICU), characteristic that is almost entirely related to the Pseudomonas aeruginosa, Enterobacter and and results in high morbidity and mortali- time during which serum concentrations exceed Klebsiella species or MRSA, suggesting again thatty.1 In this setting, antibiotic treatment of critical- the MIC (T > MIC) for the infecting organism.6,7 these represent the target pathogens for which β-ly ill patients remains a significant challenge. An The PK parameter that better drives the efficacy lactam dose adjustment is necessary to improveearly and appropriate antimicrobial therapy is of aminoglycosides is the ratio between the max- blood drug concentrations. In view of thesemandatory in the management of septic patients; imal concentrations obtained after an intra- results, broad-spectrum β-lactams should behowever, an antibiotic is appropriate not only venous administration (Cmax) and the MIC. A administered in doses larger than suggested forbecause it is active in vitro against the isolated Cmax/MIC ratio between 8 and 10 has been report- non-septic patients. According to PK modelling,pathogens, but also because the selected regimen ed to be the major determinant for optimal continuous or extended β-lactam infusions areoptimizes the killing drug activity.2 There are two antibacterial activity and clinical response.8,9 For required to optimize pathogen exposure to bac-major reasons why ICU patients are exposed to vancomycin, the area under the serum concen- tericidal concentrations of these drugs.3 However,subtherapeutic antibiotic concentrations during tration time curve (AUC) is generally calculated clinical data that have shown better outcomessepsis. First, antimicrobial dosages used in sepsis to determine the adequacy of drug levels. As it using this strategy are only from retrospectiveare derived from pharmacokinetic (PK) data may be difficult to obtain multiple serum van- studies in critically ill populations of patients withobtained from healthy volunteers or less severely comycin concentrations to determine the AUC, pneumonia.18,19 Further studies are needed toill patients, without taking into account the PK trough concentration (Cmin) monitoring has been assess the influence of continuous infusion (CI)changes that occur during sepsis, which reduce the recommended as the most accurate and practical strategy on morbidity and mortality, especially inefficacy of antibiotics. In sepsis, increased cardiac method to adjust vancomycin regimens. A Cmin patients with sepsis and infections caused by mul-output associated with increased capillary leakage above 15 µg/mL should be achieved to optimize tidrug-resistant pathogens.and peripheral effusions induces a larger volume drug activity against Gram-positive bacteria such For aminoglycosides, Cmax is determined byof distribution (Vd), which may decrease plasma as methicillin-resistant Staphylococcus aureus the administered dose and the Vd.3 The Vd oflevels of antibiotic. This hyperdynamic state can (MRSA) and Enterococcus species.10 aminoglycosides is largely increased in criticallyalso increase renal blood flow and creatinine clear- Studies on serum concentrations of broad- ill patients when compared with healthy volun-ance, resulting in elevated antibiotic elimination. spectrum β-lactams, including cefepime, cef- teers and patients with mild infections, suggest-In addition, organ (i.e., renal or hepatic) dysfunc- tazidime and piperacillin, have reported that drug ing that higher than recommended doses of thesetion can alter drug metabolism and clearance, levels were insufficient to treat less susceptible drugs should be administered to achieve optimalleading to drug accumulation and possible side strains in patients with severe infections.11–13 On Cmax.20 In a recent study, a loading dose of 25effects.3 Second, infections, especially when the other hand, serum drug concentrations of mg/kg amikacin was necessary to achieve opti-acquired in the ICU, are often caused by more meropenem were adequate in most studies in crit- mal Cmax concentrations in a prospective cohortresistant pathogens, which require higher drug ically ill patients, including patients with bacter- of septic patients with multiple organ failure.21concentrations to be killed.4 aemia and ventilator-associated pneumonia.14,15 Simulation with a standard regimen (15 mg/kg) To treat these pathogens, the combination of Furthermore, these reports excluded severely ill of amikacin resulted in insufficient peak con-broad-spectrum β-lactams with aminoglycosides patients with septic shock and those with multi- centrations in more than 90% of patients, thusand/or glycopeptides (especially vancomycin) is ple organ failure, limiting the generalizability of confirming the need to increase the dosing ofrecommended.5 However, these drugs, which are the results to other populations of critically ill aminoglycosides to optimize Cmax in septichydrophilic compounds, have a small Vd (limit- patients. In a prospective multicentre study, patients. In another study, an even highered to extracellular fluids) and are more likely to serum levels obtained after the first dose of amikacin regimen (30 mg/kg) was required tobe excreted unchanged by the kidney. Thus, PK piperacillin–tazobactam, ceftazidime or cefepime obtain adequate Cmax levels in septic patients.22alterations occurring in sepsis may profoundly were insufficient to empirically treat less suscep- Assuming the three to four-fold factor for con-affect drug concentrations and modification of tible pathogens in the early phase of severe sepsis verting doses of amikacin to gentamicin andthe drug regimen should be considered. and septic shock.16 Only meropenem achieved an tobramycin, higher doses (8–9 mg/kg) were sug- Using PK principles, different strategies are adequate serum concentration in 75% of treated gested to optimize the efficacy of these two drugsused to improve antibiotic concentrations in rela- patients. In another recent prospective study, in patients with septic shock.23,24tion to the minimal inhibitory concentration monitoring of β-lactams levels was routinely Higher than recommended doses (15 mg/kg(MIC) of the pathogen to the drug. The MIC rep- applied in the management of 236 critically ill every 12 hours) of vancomycin have been pro-resents the threshold of antibiotic levels resulting patients; dose increases were required in 50% of posed to optimize drug concentrations inin inhibition of bacterial growth under standard patients during the early phase of infection ther- patients with septic shock or with trauma andconditions.3 Experimental studies have demon- apy.17 Dose increases were more frequently MRSA pneumonia.25,26 As alternative, a CIWINTER 2011 | INTERNATIONAL JOURNAL OF INTENSIVE CARE 93
  5. 5. COMMENT 17. Roberts JA, Ulldemolins M, Roberts MS, et al. Therapeutic drugadministration (15 mg/kg loading dose followed critically ill patients to detect underdosing, which monitoring of beta-lactams in critically ill patients: proof of con-by 30 mg/kg/day) has been proposed to optimize is frequent in the early phase of therapy, and avoid cept. Int J Antimicrob Agents 2010; 36: 332–339.the effectiveness of vancomycin.3 However, the overdosing and associated side effects, including 18. Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobac-question whether intermittent dosing or CI is neurological disturbances and renal failure. Other tam for Pseudomonas aeruginosa infection: clinical implicationsbetter to improve vancomycin efficacy remains conditions found in ICU patients, such as the use of an extended-infusion dosing strategy. Clin Infect Dis 2007;unanswered. Wysocki et al. compared CI and of continuous renal replacement therapy, obesity, 44: 357–363.intermittent dosing of vancomycin in 160 burns or liver cirrhosis, may also alter the PKs of 19. Lorente L, Jimenez A, Palmero S, et al. Comparison of clinical cure rates in adults with ventilator-associated pneumonia treat-patients with severe MRSA infection and found antibiotics and should be considered for drug reg- ed with intravenous ceftazidime administered by continuous orno significant differences in clinical efficacy.27 imen adjustments. Systematic clinical PK/phar- intermittent infusion: a retrospective, nonrandomized, open-However, a faster time to achieve target drug con- macodynamic studies are required to evaluate the label, historical chart review. Clin Ther 2007; 29: 2433–2439.centrations, lower daily dose and reduced thera- beneficial effects of these dosing strategies on the 20. Marik PE, Havlik I, Monteagudo FS, et al. The pharmacokineticpy costs were reported for the CI strategy. Rello outcomes for septic patients. of amikacin in critically ill adult and paediatric patients: com-et al. suggested clinical superiority of vancomycin parison of once-versus twice-daily dosing regimens. JCI in a subgroup of patients with ventilator-asso- REFERENCES Antimicrob Chemother 1991; 27(Suppl. C): 81–89. 1. Vincent JL, Sakr Y, Sprung C, et al. Sepsis in European inten- 21. Taccone FS, Laterre PF, Spapen H et al. Revisiting the loadingciated pneumonia due to MRSA.28 Nevertheless, sive care units: results of the SOAP study. Crit Care Med 2006; dose of amikacin for patients with severe sepsis and septicdata on the optimal regimen of vancomycin 34: 344–353. shock. Crit Care 2010; 14: R53.when given by CI in patients with sepsis are 2. Khollef MH. Inadequate antimicrobial treatment: an important 22. Gálvez R, Luengo C, Cornejo R, et al. Higher than recommend-scarce. Using a Monte Carlo simulation, higher determinant of outcome for hospitalized patients. Clin Infect Dis ed amikacin loading doses achieve pharmacokinetic targetsthan recommended loading (35 mg/kg) and daily 2000; 31(Suppl. 4): S131–S138. without associated toxicity. Int J Antimicrob Agents 2011; 38: 3. Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in 146–151.(30–40 mg/kg if normal renal function) doses of the critically ill patients. Crit Care Med 2009; 37: 840–851. 23. Rea RS, Capitano B, Bies R, et al. Suboptimal aminoglycosideCI vancomycin have been suggested to rapidly dosing in critically ill patients. Ther Drug Monit 2008; 30: 4. Van Eldere J. Multicentre surveillance of Pseudomonas aerug-achieve therapeutic serum concentrations in the inosa susceptibility patterns in nosocomial infections. J 674–681.early phase of sepsis.29 However, this strategy Antimicrob Chemother 2003; 51: 347–352. 24. Buijk SE, Mouton JW, Gyssens IC, et al. Experience with a once-needs to be prospectively validated and its impact 5. Dellinger P, Levy M, Carlet J, et al. Surviving sepsis campaign: daily dosing program of aminoglycosides in critically ill patients.on drug-related toxicity further determined. international guidelines for management of severe sepsis and Intensive Care Med 2002; 28: 936–942. If higher than recommended doses for all of septic shock. Crit Care Med 2008; 36: 296–327. 25. Vázquez M, Fagiolino P, Boronat A, et al. Therapeutic drug mon- 6. Andes D, Craig WA. In vivo activities of amoxicillin and amoxi- itoring of vancomycin in severe sepsis and septic shock. Int Jthese antibiotics should be considered when treat- cillin–clavulanate against Streptococcus pneumoniae: applica- Clin Pharmacol Ther 2008; 46: 140–145.ing patients with severe sepsis and septic shock, tion to breakpoint determinations. Antimicrob Agents 26. Patanwala AE, Norris CJ, Nix DE, et al. Vancomycin dosing forroutine drug monitoring is also required to avoid Chemother 1998; 42: 2375–2379. pneumonia in critically ill trauma patients. J Trauma 2009; 67:overdosing with related toxicity. In 10% of ICU 7. Mouton JW, Punt N. Use of the t > MIC to choose between dif- 802–804.patients with renal dysfunction receiving cefepime, ferent dosing regimens of beta-lactam antibiotics. J Antimicrob 27. Wysocki M, Delatour F, Faurisson F, et al. Continuous versusserum drug accumulation occurred despite dosage Chemother 2001; 47: 500–501. intermittent infusion of vancomycin in severe staphylococcal 8. Moore RD, Lietman PS, Smith CR. Clinical response to aminogly- infections: prospective multicenter randomized study.adjustments and resulted in non-convulsive coside therapy: importance of the ratio of peak concentration to Antimicrob Agents Chemother 2001; 45: 2460–7.seizures, disappearing after drug discontinua- minimal inhibitory concentration. J Infect Dis 1987; 155: 93–99. 28. Rello J, Sole-Violan J, Sa-Borges M, et al. Pneumonia causedtion.30 Roberts et al. reported that a β-lactams dose 9. Kashuba AD, Nafziger AN, Drusano GL, Bertino JS Jr. Optimizing by methicillin-resistant Staphylococcus aureus treated with gly-reduction was applied in 24% of ICU patients when aminoglycoside therapy for nosocomial pneumonia caused by copeptides. Crit Care Med 2005; 33: 1983–1987.monitoring was routinely performed.17 Potential Gram-negative bacteria. Antimicrob Agents Chemother 1999; 29. Roberts JA, Taccone FS, Udy AA, et al. Vancomycin dosing inrenal, vestibular and neuromuscular toxicity can 43: 623–629. critically ill patients – robust methods for improved continuous 10. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin ther- infusion regimens. Antimicrob Agents Chemother 2011; 55:occur in the early or late phases of aminoglycoside apeutic guidelines: a summary of consensus recommendations 2704–2709.therapy, with a wide spectrum of severity.17 The 30. Chapuis TM, Giannoni E, Majcherczyk PA, et al. Prospective from the infectious diseases Society of America, the Americanrisk of renal dysfunction increases with concomi- Society of Health-System Pharmacists, and the Society of monitoring of cefepime in intensive care unit adult patients. Crittant hypovolaemia, pre-existing renal disease, Infectious Diseases Pharmacists. Clin Infect Dis 2009; 49: 325–7. Care 2010; 14: R51.nephrotoxics and advanced age. Cumulative dose, 11. Ambrose PG, Owens RC Jr, Garvey MJ, et al. Pharmacodynamic 31. Rybak MJ, Abate BJ, Kang SL, et al. Prospective evaluation ofespecially where there are persistent elevated considerations in the treatment of moderate to severe pseu- the effect of an aminoglycoside dosing regimen on rates oftrough concentrations, is also associated with an domonal infections with cefepime. J Antimicrob Chemother observed nephrotoxicity and ototoxicity. Antimicrob Agents 2002; 49: 445–453. Chemother 1999; 43: 1549–1555increased risk of renal toxicity so that Cmin moni- 12. Ikawa K, Morikawa N, Hayato S, et al. Pharmacokinetic and 32. Vandecasteele SJ, De Vriese AS. Recent changes in vancomycintoring is advocated to minimize drug side effects.31 pharmacodynamic profiling of cefepime in plasma and peri- use in renal failure. Kidney Int 2010; 77: 760–764. ■Finally, toxicity may occur when increasing the toneal fluid of abdominal surgery patients. Int J Antimicrobdose of vancomycin, and some studies have shown Agents 2007; 30: 270–273.that drug levels above 28 µg/mL are associated with 13. Roberts JA, Kirkpatrick CM, Roberts MS, et al. First-dose anda greater risk of renal dysfunction, especially if other steady-state population pharmacokinetics and pharmacody- namics of piperacillin by continuous or intermittent dosing inpotential nephrotoxics, such as aminoglycosides or critically ill patients with sepsis. Int J Antimicrob Agents 2010;amphotericin, are co-administered.32 Although a 35: 156–163. CORRESPONDENCE TO:slower onset of nephrotoxicity was observed in 14. Kitzes-Cohen R, Farin D, Piva G, et al. Pharmacokinetics and Fabio Silvio Taccone MDpatients receiving vancomycin by CI,27 the impact pharmacodynamics of meropenem in critically ill patients. Int J Department of Intensive Careof higher than recommended CI regimens on renal Antimicrob Agents 2002; 19: 105–110. Hôpital Erasme, Université Libre defunction has not been evaluated. 15. de Stoppelaar F, Stolk L, van Tiel F, et al. Meropenem pharma- Bruxelles (ULB) In conclusion, high or CI regimens of antibiotics cokinetics and pharmacodynamics in patients with ventilator- Route de Lennik, 808 associated pneumonia. J Antimicrob Chemother 2000; 46:are necessary to rapidly achieve therapeutic drug 1070 Brussels 150–151.levels for difficult-to-treat pathogens in patients 16. Taccone FS, Laterre PF, Durgernier T et al. Insufficient b-lac- Belgiumwith severe sepsis and septic shock. Monitoring tam concentrations in the early phase of severe sepsis and sep- E-mail: ftaccone@ulb.ac.beserum antibiotic concentrations is important in tic shock. Crit Care 2010; 14: R126.94 INTERNATIONAL JOURNAL OF INTENSIVE CARE | WINTER 2011
  6. 6. Setting a new standard for performance, safety and simplicityThe Arctic Sun 5000 brings precision Targeted Temperature Management ™to the highest level of performance available today.| Fastest initiation of treatment| Simplest programming capabilities| Easiest access to treatment data| Most comprehensive built-in training module For more information: www.medivance.com eu@medivance.com +31 703563805
  7. 7. CLINICAL NEWS From the cutting edge of research Interactive video games aid ICU patient recovery Interactive video games appear to safely enhance games included boxing, bowling and use of the Kho noted. “Our next step is to study what physical physical therapy for patients in intensive care units, balance board, which were chosen to improve the therapy goals best benefit from video games.” new US research suggests.1 patients’ stamina and balance. 1. Kho ME, Damluji A, Zanni JM, Needham DM. Feasibility and “Patients admitted to our medical intensive care “As always, patient safety was a top priority … observed safety of interactive video games for physical reha- unit are very sick and, despite early physical thera- when properly selected and supervised by experi- bilitation in the intensive care unit: a case series. J Crit Care py, still experience problems with muscle weak- enced ICU physical therapists, patients enjoyed the 2011; Epub Sept 26: DOI:10.1016/j.jcrc.2011.08.017. ness, balance and coordination as they recover,” challenge of the video games and welcomed the said lead researcher Dr Michelle E. Kho of Johns change from their physical therapy routines,” said Hopkins University. “Our study suggests that inter- study author Dr Dale M. Needham. active video games may be a helpful addition.” The video game therapy activities are short in dura- © Paul Rapson/Science Photo Library Over a one-year period, the researchers identi- tion, which is ideal for severely deconditioned patients, fied a select group of 22 critically ill adult patients Dr Needham said. They are also very low cost com- who received video games as part of routine physi- pared to most ICU medical equipment, he added. cal therapy. They were mostly males aged 32 to 64 More research is needed into whether the video years old. game therapy helps patients to improve their abili- The 42, 20-minute physical therapy sessions ties to do tasks that are most important to then, the included use of the Nintendo Wii and Wii Fit video researchers caution. games under supervision of a physical therapist. “Our study had limitations because the patients were Almost half the sessions included patients who not randomly selected, the video game sessions were The Nintendo Wii: a safe addition to physical therapy were mechanically ventilated. The most common infrequent and the number of patients was small,” in the ICU. Timing crucial for family Calorific intake essential for ICU patients consent in organ donation The amount of calories that intensive care patients receive is essential for improving their chances of recovery, according to Canadian research.1 The time at which organ donation in brain dead lected retrospectively from 228 patients declared Patients who receive more calories while in inten- donors is first discussed with family members could brain dead between 1987 and 2009 in the Erasmus sive care have lower mortality rates than those who affect whether or not they consent to donation, MC University Medical Centre. receive less of their daily-prescribed calories, con- according to a Dutch study. The Donor Register was introduced in the clude the researchers. Discussing the issue of donation with relatives of Netherlands in 1998, which increased patient-con- “Our finding is significant as there have been a victims of catastrophic brain injury earlier on in the sent rates more than seven-fold, from 5.7% to 41%, number of previous studies in the area of critical process may have a negative effect on the consent the researchers found. care nutrition that have produced conflicting clinical rate, the authors conclude. They also observed that over the past 15 years recommendations and policy implications,” said In the study, the researchers analysed data col- there was a decline in donation after brain death study lead author Dr Daren Heyland of Queen’s from 89% to 58%; in contrast, donation after circu- University and Kingston General Hospital. “Since latory death increased from 11% to 42%. caloric delivery is essential for improving the The timing of discussion about organ donation chances of these critically ill patients, it’s vital that with relatives changed after 1998 from first being we know what the optimal level is.” mentioned after the completion of all tests, to after The research team examined the records of 7872© Klaus Guldbrandsen/Science Photo Library determination of loss of consciousness and the mechanically ventilated, artificially fed patients in absence of brainstem reflexes but before completion 352 ICUs in 33 countries. They found that patients of confirmatory tests. receiving at least two-thirds of their prescribed calo- Lead author Dr Erwin Kompanje said, “It is unclear rie intake had reduced mortality rates when com- whether the observed shift contributed to the high pared with patients receiving less than one-third of refusal rate in the Netherlands and the increase in their prescribed calorie intake. The optimal caloric family refusal in our hospital after 1998 … it is pos- intake was identified to be about 80 to 85% of total sible that this may have a counterproductive effect.” prescribed calorie intake. 1. de Groot YJ, Lingsma HF, van der Jagt M, et al. Remarkable changes in the choice of timing to discuss organ donation with 1. Heyland D, Cahill N, Day AG. Optimal amount of calories for criti- When to discuss organ donation with relatives is the relatives of a patient: a study in 228 organ donations in 20 cally ill patients: depends on how you slice the cake! Crit Care Med crucial. years. Crit Care 2011; 15: R235. 2011; Epub June 23: DOI:10.1097/CCM.0b013e318226641d. 96 INTERNATIONAL JOURNAL OF INTENSIVE CARE | WINTER 2011
  8. 8. INDUSTRY NEWS An update on recent industry initiatives Value of closed loop ventilation recognised by major award The winner of the Swiss Technology Award 2011 has created by Hamilton Medical, and as well as the clin- advanced lung protective strategies and patient adap- been announced as the INTELLIVENT®-ASV introduced ical benefits, it has a positive impact on costs as well. tive modes. The device is the ideal choice for extreme by Hamilton Medical. It is the first complete closed loop Costs in the ICU include labour, materials and also environments, where ICU ventilation is essential and ventilation solution, that offers automated adjustment indirect costs from other departments. The impact of reliable data. of oxygenation and ventilation. Today, conventional intelligent ventilators can be substantial as they can mechanical ventilation still requires a great deal of reduce the time a patient spends on the ventilator by expertise and the manual adjustment of ventilator set- reducing ventilator interractions by staff as well as pro- tings. This can be challenging, as it is impossible for a viding innovative diagnostic tools. respiratory clinician to be at the bedside all the time. The award was in recognition of only one aspect of Now there is a solution to the problem as the device Hamilton Medicals programme of innovation. It does not provides guidance when complex decisions are made. end at the hospital doors, but responds to the require- Equally important it not only gives recommendations, ment for ready access to appropriate modes of therapy but also adjusts ventilation settings automatically. The for ventilated patients outside the hospital environment. INTELLIVENT-ASV even applies comprehensive lung The HAMILTON-T1 delivers a cost-effective solution protective strategies automatically and reduces the risk that is appropriate for all patients from paediatric to of operator errors while encouraging early weaning. adult. It is suitable for mobile ICU ambulances, heli- The Hamilton Medical team receives the Swiss The device is based on innovative ASV technology copters and long distance jets. The device also includes Technology Award for 2011.Compact monitor Medication data flies over the airwavesgives instant access Medication errors remain a continuing hazard in hos- pitals and there are a variety of products available to address it. This creates the problem of how to choose the most suitable infusion system for a particular appli-A certain percentage of patients invariably have to the hospital information loop. This has meant greater cation. The latest system to make its appearance ismove around the hospital for a variety of reasons. mobility for patients and more time available for clin- the new Medfusion® 400 wireless syringe infusionMonitoring is required during their transport or within ical and nursing procedures. pump with the PharmGuard® infusion managementthe hospital, in a progressive care area or during super- software suite introduced by Smiths Medical. In com-vised recovery from an acute event or surgical proce- mon with other infusion devices it is designed to helpdure. Recognising this need Philips has introduced the prevent errors. The difference is that at the same timeIntelliVue MX40 patient monitor. It is a wearable mon- it facilitates the forwarding and receipt of medicationitor which combines the benefit of the IntelliVue X2 and delivery information more efficiently. This is achievedPhilips Telemetry into a single, compact wearable via the wireless Ethernet connectivity.monitor. The benefits it brings are considerable. It Financial and other considerations are making theallows the clinician to better manage patient alerts and challenge of improved patient outcomes more difficultis designed to support effective infection control. to achieve. The easy access to medication data can There is easy access to such important data as ECG, help clinicians to make these improvements. This sys-SpO2 and non-invasive blood pressure. Patient alerts tem with its wireless connectivity allows hospitals toare highlighted at both the bedside and the central capture many types of infusion data and facilitates easymonitoring station. The clinician is alerted to changes reporting for evidence based practice improvements.in the patient conditions based on real-time surveil- It also smoothes the update of drug libraries andlance. In total the monitor makes an important contri- improves both patient safety and clinical care by thebution to a streamlined data flow. The Intellivue quick and easy update of pumps.Information Centre is an integral part of the MX40 solu-tion as it facilitates interfacing with the hospital EMR(electronic medical record). PLEASE SEND YOUR NEWS ITEMS TO: The development of the system was the result of a Guy Wallisresearch initiative that took two different technologies Editorial Directorand combined them into a single innovative device that Alerts are highlighted at the bedside and the central g.wallis@greycoatpublishing.co.ukcould speed vital patient data around the key points of monitoring station as well.98 INTERNATIONAL JOURNAL OF INTENSIVE CARE | WINTER 2011
  9. 9. REVIEWSurgical and intensive care strategiesto prevent renal failure Acute kidney injury (AKI) refers to a sudden decline in kidney meta-analysis established the usefulness of NGAL as a diag-N Brienza MD, PhD, function causing disturbances in fluid, electrolyte, and nostic and prognostic tool in cardiac surgical and critical-MT Giglio MD,L Dalfino MD, acid–base balance due to a loss in small solute clearance and ly ill patients, as well as in patients with contrast-relatedEmergency and Organ decreased glomerular filtration rate. Its occurrence in surgical renal damage, while no conclusions can be drawn for non-Transplantation Department, and critically ill patients is common and it is associated with a cardiac surgical patients.8 In a large multicentre analysis,Anesthesia and Intensive Care substantial increase in morbidity and mortality. Although the the same group confirmed that a positive NGAL findingUnit, University of Bari, pathophysiology of AKI is complex, subsequent injury identified approximately 40% more AKI cases than creati-Bari, Italy responses are likely to involve similar mechanisms. Major nine alone and that these patients were at greater risk of contributors that precede renal injury are hypotension, death compared with control subjects.9 Very recent tri- ischaemia/reperfusion, inflammation and toxins. Appropriate als10,11 suggest that a single NGAL measurement at ICU and early identification of patients at risk for AKI provides an admission can predict later-onset AKI as well as ICU mor- opportunity to prevent subsequent renal insults and impact tality, both alone or in combination with other AKI overall intensive care unit morbidity and mortality; strategies biomarkers. to prevent AKI are therefore of pivotal importance. Key components of optimal prevention and management of the EPIDEMIOLOGY intensive care unit patient with AKI include maintenance of Traditionally, AKI has been extensively studied in cardiac renal perfusion and avoidance of precipitating factors. surgery, where it has a high occurrence (1–30%) and is Whereas management of AKI remains limited primarily to highly predictive of other complications.12 In general sur- supportive care, many potential therapies and interventions gical patients, AKI – defined as a creatinine increase of at are on the horizon. For now, recognition of risk factors, least 2 mg/dL or need for dialysis – occurs in 1% of patients excellent supportive care and avoidance of clinical conditions and is associated with an eight-fold increase in mortality, known to cause or worsen AKI remain the cornerstones of independent of underlying comorbidities.13 Although management of AKI. small as an absolute number, the rate of AKI is similar to that of other ominous perioperative complications, such as adverse cardiac events or venous thromboembolism.14 A cute kidney injury (AKI) is a serious complication in surgical and critical care patients, accounting for In patients admitted to the ICU after non-cardiac surgery, 18–47% of all hospital-acquired AKI,1,2 augmenting the AKI rate is 7.5% and AKI is an independent risk factor hospitalisation costs3 and increasing mortality.4 for mortality at 6 months’ follow-up.15 More interesting- Clinical manifestations of acute renal involvement range ly, the occurrence of postoperative AKI, independent of its from short periods of oliguria to the need for renal replace- evolution, seems to affect outcomes.15 Knowing the exact ment therapy (RRT). However, these manifestations have timing of kidney insult (i.e., surgery) would make preven- different clinical impacts, since a common transient post- tion of postoperative kidney injury easier than in other set- operative oliguria may not be synonymous of abnormal tings. However, one major problem is that we do not know renal function but the appropriate response to hypoperfu- exactly which patients will really obtain a benefit. Whereas sion of a kidney that is ‘doing its job’. The need for RRT,5 in cardiac surgery preoperative renal risk is carefully strat- on the other hand, as well as subtle increases in serum cre- ified,12 this evaluation is lacking in non-cardiac surgery, atinine, usually perceived as fluctuations within the ‘nor- although a specific risk index for AKI including congestive mal range’,4 are both associated with increased mortality heart failure, emergency surgery or the complexity of and morbidity. On the basis of glomerular filtration rate, surgery, mild or moderate chronic renal insufficiency and creatinine level and urine output, the RIFLE (Risk, Injury, diabetes mellitus under therapy has recently been pro- Failure, Loss and Endstage Kidney Disease) classification posed.13 defines three grades of increasing severity and two outcome AKI often complicates the course of critical illness and, classes, all associated with increased hospital mortality.6 The although previously considered as a marker rather than a AKI Network has modified RIFLE by adopting the term cause of adverse outcomes, it is independently associated ‘AKI’ to cover the entire spectrum of acute renal failure7 and with an increase in both morbidity and mortality.16 The by including only three stages representing an increasing major causes of AKI in the ICU include renal hypoperfu- degree of renal impairment, from small increases in creati- sion, sepsis/systemic inflammatory response syndrome and nine to the need for RRT. direct nephrotoxicity, although in most cases the aetiology However, the rise in creatinine lags behind the process is multifactorial.17,18 In a recent multicentre study, 42% of leading to AKI, since it is revealed only after a substantial 33,375 septic patients developed concomitant AKI.19 Risk fall in glomerular filtration rate has occurred. Therefore, factors for the development of septic AKI included age, new biomarkers for AKI early diagnosis have been pro- comorbidities and a higher severity of illness. Since most of posed with the aim of identifying an ongoing kidney insult these factors are not modifiable, AKI prevention should before creatinine variation. The most promising is neu- mostly benefit from the avoidance of potential nephrotox- trophil gelatinase-associated lipocalin (NGAL). A recent ic conditions and prompt recognition. ➟100 INTERNATIONAL JOURNAL OF INTENSIVE CARE | WINTER 2011
  10. 10. STRATEGIES TO PREVENT RENAL FAILUREPREVENTIVE STRATEGIES Haemodynamic optimisationA major problem in AKI prevention is the lack of evidence- The kidney normally receives 20–25% of total cardiacbased strategies. In 2005, a systematic review did not find output. However, the medullary portion of the nephronsany reliable evidence from the available literature to suggest is at risk of hypoperfusion because of low blood flowthat dopamine, diuretics, calcium-channel blockers or and high oxygen demand and extraction. In the perioper-angiotensin-converting enzyme inhibitors can protect the ative setting, the increase in oxygen demand may put thekidneys.20 Recent recommendations for the protection and kidney at further risk of hypoxia.30 Haemodynamic optimi-prevention of AKI in ICU patients are all ‘negative’ 1A rec- sation or goal-directed therapy (GDT) is the perioperativeommendations (strong recommendation with a high monitoring and manipulation of physiological haemody-degree of evidence), and the few ‘positive’ clinical indica- namic parameters by means of fluids and inotropic drugs,tions have been downgraded to suggestions with a low grade with the aim of achieving adequate oxygen delivery toof evidence.21,22 cope with the increase in oxygen demand and prevent organ failure.31How many and which fluids? A recent meta-analysis demonstrated that GDT decreas-Both relative and overt hypovolaemia are significant risk es the risk of postoperative renal impairment (Table 1).32factors for the development of AKI. Consequently, timely Interestingly, this nephroprotective strategy was reportedfluid administration is a preventive measure that should be to be effective in high-risk surgical patients and when start-effective through restoring the circulating volume and min- ed preoperatively to the first hours postoperatively.imising drug-induced nephrotoxicity. In ICU patients, Moreover, targeting the optimisation to physiological val-however, AKI commonly involves multiple mechanisms, ues of cardiac output revealed as much nephroprotectionincluding hypovolaemia and various types of shock. For as adopting supranormal goals of cardiac output. Becauseexample, sepsis and trauma can cause AKI through a com- of potential complications of fluid overload, myocardialbination of renal hypoperfusion and the release of endoge- ischaemia and excessive use of catecholamine, which are notnous nephrotoxins. Thus, correction of fluid deficit, while devoid of risks in terms of renal function,33 aggressive useessential, will not always prevent renal failure. Moreover, it of fluids and catecholamines in an attempt to increase car-is often difficult for clinicians to determine the amount of diac output to supranormal values can be avoided. Despitefluids to administer to a given patient. From a kidney stand- the obvious limitations of all the meta-analysis regardingpoint, on one side failure to prescribe adequate intravenous methodological differences among studies, publication biasfluid can place a patient at risk of hypovolaemia, while on or suboptimal methodological quality of the studies, peri-the other side excessive fluid infusion may promote third- operative GDT is, at the moment, the only evidence-basedspace loss and intra-abdominal hypertension (IAH), a well- strategy able to reduce kidney injury in postoperativeknown risk factor for AKI (see below). Currently, an patients. Moreover, evidence suggests that in surgicalindividualised, timely fluid ‘replacement’ therapy by titrat- patients, perioperative GDT with epinephrine, dopexam-ing volume to physiologic flow-related endpoints with ine or dobutamine may improve renal outcome,32,34 callingappropriate monitoring23 may be a rational choice. for further trials to better clarify this issue. The question of fluid infusion concerns not only the In patients with persistent hypotension despite volumequantity of fluids, but also their quality. Aggressive crystal- optimisation, vasopressors are often employed to increaseloid resuscitation may increase intra-abdominal pressure mean arterial pressure and/or cardiac output, with the goaland impair renal function, and colloids, while maintaining of ensuring optimal renal perfusion. In septic patients, nore-the plasma volume more efficiently, may per se impair renal pinephrine has been traditionally used to increase bloodfunction. Recent randomised controlled trials (RCTs) have pressure with improvement of creatinine clearance.35 Anreported fewer marked changes in postoperative kidney RCT comparing dopamine with norepinephrine as the ini-function with 6% hydroxyethyl starch (HES) 130/0.4 com- tial vasopressor in septic shock showed no significant dif-pared with gelatine in both cardiac and vascular surgery ferences between groups with regard to renal function orpatients24,25 The most update-to-date evaluation of the rela- mortality, even if the use of norepinephrine was associatedtionship between colloids and kidney function shows that, with a lower incidence of arrhythmias.36 The results ofmore than the quality, it is the mean colloid cumulative dose VASST (Vasopressin and Septic Shock Trial) suggest that,that is associated with AKI.26 A recent Cochrane review stat- compared with norepinephrine, vasopressin may reduceed that colloids carry an increased risk of AKI in septic the progression to severe AKI only in a subgroup of patientspatients compared to non-septic surgical and trauma with less severe septic shock.37 The use of norepinephrinepatients.27 However, the small number of studies and the to improve renal oxygen delivery and renal oxygenation haslow event-rate claims for larger studies in non-septic set- been tested in other kinds of vasodilatory shock (i.e., post-ting may have hampered the statistical power of these find- cardiac surgery patients) with convincing results.38ings. Recently, a pilot RCT performed in cardiac surgical Vasodilatorspatients undergoing cardiopulmonary bypass suggested In recent years, a role for specific vasodilating drugs on kid-that intravenous sodium bicarbonate is associated with a ney function has emerged. Fenoldopam mesylate is a selec-lower incidence of acute renal dysfunction.28 This result tive DA-1 agonist that increases both medullary and corticalwarrants further investigation with adequately powered blood flow and reduces oxygen demand.39 A meta-analysisRCTs and in other surgical settings. The benefit of sodium including 1,290 patients found that fenoldopam significant-bicarbonate has been extensively studied in contrast- ly reduced the need for RRT and in-hospital mortality40 andinduced nephropathy, and recent inconclusive evidence a later review41 confirmed a beneficial effect in cardiac sur-confirms a benefit of sodium bicarbonate over normal gical patients, but no conclusion can be drawn regardingsaline.29 non-cardiac surgery. ➟WINTER 2011 | INTERNATIONAL JOURNAL OF INTENSIVE CARE 101
  11. 11. STRATEGIES TO PREVENT RENAL FAILURE Table 1. Subgroup analyses of pooled odds ratios of renal injury in perioperative haemodynamic goal-directed studies32 Treatment Control Q statistic Statistical (n/N) (n/N) OR (95% CI) p-value p-value I2 (%) power (%) High-quality RCTs (Jadad 102/1,741 150/1,699 0.66 (0.50–0.87) 0.003 0.75 0 99.7 score 3) Renal injury according to 97/1,893 145/1,839 0.66 (0.50–0.86) 0.002 0.76 0 99.8 AKIN Preoperative optimisation 94/1,347 117/1,289 0.70 (0.53–0.94) 0.02 0.41 0 75.6 Intraoperative or 21/770 58/814 0.47 (0.27–0.81) 0.006 0.80 0 100 postoperative optimisation High-risk patients 102/1,393 158/998 0.64 (0.49–0.84) 0.001 0.53 0 99.8 Non-high-risk patients 13/724 17/686 0.69 (0.31–1.54) 0.37 0.61 0 19.1 Pulmonary artery catheter 103/1,640 151/1,629 0.62 (0.43–0.90 0.01 0.35 10.3 98 monitoring Other monitoring devices 12/477 24/474 0.52 (0.25–1.07) 0.07 0.87 0 73 Fluids only 6/334 12/333 0.55 (0.20–1.47) 0.23 0.74 0 31 Fluids + inotropes 109/1,783 163/1,770 0.65 (0.50–0.85) 0.002 0.50 0 100 Fluids + dobutamine 12/511 42/518 0.36 (0.18–0.75) 0.006 0.57 0 100 Supranormal targets 30/354 55/353 0.49 (0.29–0.83) 0.008 0.54 0 98.2 Normal targets 85/1,763 120/1,750 0.70 (0.52–0.94) 0.02 0.71 0 94.5 AKIN = Acute Kidney Injury Network; CI = confidence interval; OR = odds ratio; RCT = randomised controlled trial Atrial natriuretic peptide (ANP) is another ideal substance um by reperfusion (e.g., after haemorrhagic shock) or by to counteract the initiation phase of AKI by causing vasodi- inflammatory mediators of injury (e.g., during sepsis/sys- latation of the preglomerular artery, inhibition of the temic inflammatory response syndrome or major surgery) renin–angiotensin axis and prostaglandin release.42 A recent associated with a positive fluid balance can lead to gut oede- Cochrane review showed that low-dose ANP after major ma and IAH. IAH, by impairing systemic haemodynamics surgery significantly reduced the requirement for RRT in and renal function, may foster a fluid-overload condition, prevention studies, but not in treatment studies.43 However, leading to a vicious cycle that perpetuates IAH itself and renal this result was mostly driven by the efficacy of low-dose ANP injury.47 Therefore, when IAH is present in an oliguric in patients undergoing cardiovascular surgery. patient, intra-abdominal pressure should be monitored carefully and crystalloid use should be avoided or limited. Metabolic control Specific medical treatments and surgical options should be In 2001, an RCT in surgical ICU patients compared tight considered to decrease intra-abdominal pressure.48 blood glucose control with insulin (blood glucose 80–110 mg/dL) versus standard care (blood glucose 150–160 Drugs mg/dL), demonstrating an improved survival rate and a The contribution of treatment-induced renal injury as a 41% reduction in AKI requiring RRT in the intensively con- preventable cause of AKI is frequently underestimated. In trolled group.44 These positive findings have recently been severe AKI, nephrotoxic drugs are contributing factors in questioned by the NICE-SUGAR trial,45 which included up to 19–25% of cases.2,49 In surgical and critically ill surgical patients but was not limited to them. This trial patients, drug-induced AKI is mediated by inherent drug found that a blood glucose target of 180 mg/dL or less result- nephrotoxic potential, disease states and impaired drug ed in lower mortality than an intensive target of 81–108 pharmacokinetics, leading to overdosing. mg/dL, with no effect on RRT. A recent meta-analysis, Drugs may exert a direct nephrotoxic effect by several which included the NICE-SUGAR trial, tried to put the con- mechanisms. Most commonly, renally excreted drugs can troversial results in a different perspective by analysing sub- exert direct toxic effects on renal tubules, inducing cellular groups of mixed, medical and surgical ICU patients.46 The injury and death in acute tubular necrosis, or can induce analysis concluded that a beneficial effect, if any, on mor- renal interstitium inflammation in acute interstitial nephri- tality of this therapy may be restricted to patients in the sur- tis. Moreover, hypertonic solutions may cause osmotic gical ICU. nephrosis and tubular obstruction by drug precipitation. Drugs may also be indirectly nephrotoxic by impairing Intra-abdominal hypertension intrarenal blood flow, thus making the kidneys vulnerable Shock and IAH, by reducing abdominal perfusion pressure, to ischaemia and injury in low-flow states such as sepsis, are the strongest independent predictors of AKI.47 ‘Third- volume depletion, major surgery, trauma and acute decom- space’ losses from compromised bowel capillary endotheli- pensated heart failure.50 ➟102 INTERNATIONAL JOURNAL OF INTENSIVE CARE | WINTER 2011
  12. 12. STRATEGIES TO PREVENT RENAL FAILURE Table 2. Primary pathogenetic mechanisms, specific clinical features and risk factors, preventive measures in high-risk patients and management of drug-induced AKI22,26,50,51 Primary Drug Clinical features Specific risk factors AKI prevention in high-risk patients/management mechanism Radiocontrast dye Haemodynamically Radiocontrast dye Onset: 24 hours Advanced age, diabetes Address the issue of whether contrast exposure is mediated mellitus, multiple mieloma, mandatory nephrotic syndrome, Discontinue all other nephrotoxics if possible haemodynamic instability Use the smallest volume of iso-osmolar agents High osmolality and/or high volume ( twice the baseline Perform preprocedural hydration with crystalloid GFR in mL) of radiocontrast dye solutions (sodium chloride or sodium bicarbonate infused at 3 mL/kg/hr for 1 hour), plus high-dose NAC Number of risk factors (1,200 mg) administration, followed by postprocedural hydration (1 mL/kg/hr for the subsequent 6 hours) Monitor renal function at 24–72 hours ACE inhibitors, Usually reversible upon Bilateral renal artery stenosis Consider drug requirement carefully angiotensin-receptor discontinuation Discontinue if SCr >30% from baseline or blockers hyperkalemia develops NSAIDs, COX-2 Onset after a few doses Severe cardiovascular or Consider drug requirement carefully (prefer inhibitors Usually oliguric hepatic failure acetominophen and/or narcotics) Usually reversible upon Type (aspirin the least toxic, Begin with a low-dose of short half-lifes NSAIDs discontinuation indomethacin the most toxic), (salycilates, sulindac) dose and duration of therapy Use half doses or avoid ketorolac, avoid indomethacin Concomitant nephrotoxics Immediatly stop NSAID therapy Correct volume depletion Calcineurin inhibitors Onset: few weeks or Dose and serum levels Perform TDM (cyclosporine, months Concomitant nephrotoxics Avoid other nephrotoxins tacrolimus) Usually oliguric Perform dose reduction or drug discontinuation Reversible after dose reduction or discontinuation Acute tubular Aminoglycosides Onset: 5–10 days Advanced age Consider alternative antimicrobials necrosis Non-oliguric Type of aminoglycoside Use extended-interval dosing (i.e., once-daily dosing) (streptomycin the least toxic, From mild and rapidly Perform TDM, and titrate dose basing on trough levels neomycin the most toxic) reversible to severe and renal function forms requiring RRT and Persistently high trough serum Avoid concomitant nephrotoxins a prolonged recovery levels time Discontinue and choose alternative antimicrobials if Frequency of administration, possible, when severe AKI ensues Usually reversible upon large cumulative doses, long early discontinuation and/or repeated courses of therapy Concomitant nephrotoxics High-dose vancomicin Onset: 4–8 days Advanced age Perform TDM and titrate dose based on renal function (daily dose 4 g or Usually reversible upon Obesity and ideal body weight 30 mg/kg, or target discontinuation Discontinue and choose alternative antimicrobials if trough concentrations High APACHE II score possible, when severe AKI ensues of 15–20 mg/L) Trough levels >15 mg/L Duration of therapy Concomitant aminoglycoside therapy Amphotericin B Frequency: 80% Hypokalemia Consider alternative antifungals Usually oliguric Large single and cumulative Prefer lipid-based formulations doses Perform sodium loading with intravenous hydration Concomitant nephrotoxics before each dose Prescribe prolonged infusion times and daily renal function monitoring Avoid concomitant nephrotoxins ➟104 INTERNATIONAL JOURNAL OF INTENSIVE CARE | WINTER 2011

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