Munuaiskorvaushoito lapsilla. Heikki Valkonen SULAT 2015 Helsinki

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1 Munuaiskorvaushoito lapsilla Heikki Valkonen SULAT 2015 Helsinki

2 Sisältö Sisältö Lasten akuutti munuaisvaurio Eri munuaiskorvaus modaliteetit Ei sisälly Biomarkkerit Krooninen munuaisten vajaatoiminta Antikoagulaatio

3 Yleistä Tutkittua tietoa vähän, lähinnä retrospektiivisiä tai rekisteritutkumksia Hemodialyysi käytännöt ekstrapoloitu aikuispuolelta Lapsilla käytetyt dialyysimuodot Peritoneaalidialyysi Intermittoiva hemodialyysi Jatkuva hemodialyysi

4 Akuutti munuaisvaurio (AKI) Merkittävä vaikutus Kuolleisuuteen Tehojakson pituuteen Ventilaattori hoidon pituuteen

5 AKI - luokittelu RIFLE prifle AKIN KDIGO

6 prifle Estimated CCL Risk eccl decrease by 25% Injury eccl decrease by 50% Urine output <0.5 ml/kg/h for 8 h <0.5 ml/kg/h for 16 h Failure Loss End stage eccl decrease by 75% or eccl < 35 ml/min/1.73m 2 Persistent failure >4 weeks End-stage renal disease (persistent failure >3 months) eccl = (k * height (cm)) / Crserum (mg/dl) <0.3 ml/kg/h for 24 h or anuric for 12 h infant (LBW < 1y) 0.33; Infant (term < 1y) 0,45 Child or Adolescent Girl 0.55 Adolescent Boy 0.7

7 tors unique to neonatal renal physiology, as described earlier. At this time, there is general acceptance that an SCr increase of 0.3 mg/dl or more (KDIGO AKI stage 1) is sufficient Vastasyntyneiden to trigger concern for AKI in neonatal patients in AKI:n the appropriate clinical context. 42 Thus, modifications to the KDIGO definition have been made in a proposed neonatal AKI definition as follows. 8 Because SCr normally declines over the first week of life, 43 each SCr is compared with the lowest previous value. In addition, because luokittelu Box 1 Proposed neonatal AKI classification Stage SCr Urine Output 0 No change in SCr or increase <0.3 mg/dl 0.5 ml/kg/h 1 SCr increase 0.3 mg/dl within 48 h or <0.5 ml/kg/h for 6 12 h SCr increase reference SCr a within 7 d 2 SCr increase 2 to 2.9 reference SCr a <0.5 ml/kg/h for 12 h 3 SCr increase 3 reference SCr a or SCr 2.5 mg/dl or Receipt of dialysis <0.3 ml/kg/h for 24 h or anuria for 12 h a Baseline SCr is defined as the lowest previous SCr value. Modified from Jetton JG, Askenazi DJ. Update on acute kidney injury in the neonate. Curr Opin Pediatr 2012;24(2): ,3 mg/dl = 26,52 µmol/l 1,0 mg/dl = 88,4 µmol/l 2,5 mg/dl = 221 µmol/l

8 Lasten AKI 2106 lasta (Ei sydänkirurgisia potilaita) AKI 17.9% (377 / 2106) (AKIN classification) Kuolleisuus 10.3% AKi ryhmässä vs. 1.7% OR 3.7 Pidempi teho-hoito aika Pidempi ventilaattorihoidon tarve Alkandari et al. Critical Care 2011, 15:R146

9 bscr measured and not being a postoperative patient (odds ratios shown in Table 1). shows that, overall, almost all AKIs occurred within the first two or three days after PICU admission. Alkandari et al. Critical Care 2011, 15:R146 Lasten AKI Page 6 of 12 Table 1 Patient characteristics by AKI status and variable associations with AKI a,b Mean (± SD), median or n (%) e Characteristics (N = 2,106) AKI (n = 377) Non-AKI (n = 1,729) P value c AKI risk factors adjusted ORs (95% CI) d AKI risk factors Age, years 5.0 (5.5), (5.7), (0.97 to 1.01) PRISM score f 7.9 (6.3), (4.6), 4 < (1.08 to 1.13) g Centre Hospitalier Universitaire Ste-Justine 116 (30.8%) 620 (35.9%) (0.61 to 1.02) Female gender 161(42.7%) 757 (43.8%) (0.79 to 1.27) Mechanically ventilated 226 (60.0%) 747 (43.2%) < (1.18 to 1.94) g Measured bscr 218 (57.8%) 757 (43.8%) < (1.72 to 2.86) g Postoperative (noncardiac) 102 (27.1%) 624 (36.1%) (0.51 to 0.90) g Admission for trauma 15 (4.0%) 132 (7.6%) (0.33 to 1.07) Documented infection 39 (10.3%) 67 (3.9%) < (1.23 to 2.99) g Outcomes Length of mechanical ventilation, days 5.4 (9.7), (8.6), 0 < Not applicable PICU length of stay, days 9.7 (21.7), (16.2), 2 < Not applicable PICU mortality 39 (10.3%) 30 (1.7%) < Not applicable a AKI = acute kidney injury; bscr = baseline serum creatinine; I = confidence interval; OR = odds ratio; PICU = pediatric intensive care unit; PRISM = Pediatric Risk of Mortality; SD = standard deviation; b AKI was defined according to the traditional Acute Kidney Injury Network staging system by using the lowest SCr level in the previous three months or ageand gender-based normative values as bscr. Patients with no SCr data available were assumed not to have developed AKI; c P values are based on the univariate comparison test Alkandari performed between AKI andet non-aki al. groups; Critical d adjusted ORs were calculated Care based on2011, multiple logistic regression 15:R146 analysis to evaluate independent risk factors for AKI; e n (%) data represent the column percentage (for example, proportion of AKI patients who were female and proportion of AKI patients who were treated at Centre Hospitalier Universitaire Ste-Justine); f only 2,085 patients had PRISM scores available; g statistically significant (P < 0.05) ORs represent independent AKI risk factors.

10 Vastasyntyneen AKI Perinataali hypoksia VLBW ( < 1500g ) Synnynnäiset sydänviat Sydänkirurgia joka vaatii sydänkeuhkokenetta (23-52%) ECMO (71%) Sepsis Synnynnäiset munuaisten ja virtsateiden anomaliat Jetton JG, Askenazi DJ. Clin Perinatol 41 (2014)

11 Nestelasti ja AKI CRRT hoidettuja lapsia N= Sepsis(31.2%) Kantasolu siirto (15.2%) Sydämen vajaatoiminta (11.5%) Hemato/Onkologia (8.8%) Lineaarinen suhde mortaliteetilla ja nestelastilla Figure 1. Mortality rates of pediatric intensive care unit patients receiving continuous renal replacement therapy 1% nestelasti lisä -> 3% lisäys subdivided by degree of fluid overload. Error bars represent 95% confidence intervals for the mortality rate in each fluid mortaliteettiin overload group. There was a statistically significant difference in mortality among the 3 groups. Patients with 20% SM Sutherland, et al. American Journal of Kidney Diseases, fluidvol overload 55, No had2 significantly (February), higher 2010: mortality pp than patients with 10% fluid overload and those with 10%-20% fluid a o r 0 p h ( c w ( C f s s o

12 Dialyysi indikaatiota Hoitoresistentti asidoosi ( ph < 7.1) tai hoidosta huolimatta nopeasti syvenevä asidoos Anuria tai oliguria Hoitoresistentti hyperkalemia (> 6-6.5) Kliinisesti merkittävä nesteretentio (keuhkopöhö, nouseva IAP), joka ei hallittavissa diureetein Uremia (enkefalopatia, pahoinvointi, kouristukset, perikardiitti, vuoto)

13 Koska aloittaa munuaiskorvaushoidot? Edellisten indikaatioiden täyttyessä? Nestelasti? 10% 20% > 20% Kunnes furosemidilla ei vastetta? Kuinka kauan voidaan odottaa spontaania munuaisten toipumista?

14 Coarctation repair 6 Truncus arteriosus repair 5 Anomalous origin of coronary artery from pulmonary artery repair 5 Complete atrioventricular canal repair 5 Varhainen PD Ventricular septal defect and coarctation repair 5 Ventricular septal defect 5 Valvuloplasty, mitral 4 Konno procedure 3 sydänkirurgian Absent pulmonary valve jälkeen repair 2 Other 11 Abbreviation: AKI, acute kidney injury. Early vs late PD Early = Leikkauspäivänä Late = 1.POP tai myöhempi Retrospektiivinen tutkimus 3550 sydänleikkausta 146 PD hoidettua lasta 109 Early PD 43.5% pienempi kuolleisuus varhaisessa PD:ssä Survival probability Early PD Delayed PD No. at risk: Early PD 37 Log-rank P = Delayed PD Days of follow-up Figure 2 Ninety-day survival among patients with early and delayed peritoneal dialysis. Survival is shown using Kaplan Meier curves. Patients with peritoneal dialysis (PD) Bojan M, et al. Kidney International (2012) 82, ; /ki ; peritone The prop dialysis o a Relative at the more t Propen The pr betwee Early P proced and de extraco associa was co relative had go of the v overlap s.d. ¼ 0 s.d. ¼ 0 tive, a betwee weight rendere no furt Sho betwee signific and a s rate in PD gro largest group

15 Peritoneaali dialyysi Ensisijainen ja yleisin vaihtoehto pienillä lapsilla Yksinkertainen aloittaa Halpa Soveltuu myös hemodynaamisesti epävakaalle potilaalle Ei vaadi antikoagulaatiota

16 Peritoneaali dialyysi PD-katetrin laitto suhteellisen yksinkertainen toimenpide Ei vastaa teholtaan hemodialyysiä Usein saavutetaan riittävä puhdistuma ja nesteen poisto Nesteenpoistoa ei voi kontrolloida yhtä tarkasti kuin hemodialyysillä

17 Peritoneaali dialyysi Glukoosi osmoottisena molekyylinä Muodostaa voimakkaan osmoottisen paine gradientin vatsakalvolla -> Ultrafiltraatio Puskurit laktaatti bikarbonaatti Elektrolyytit Natrium Kalium Kalsium

18 Edellytykset peritoneaali dialyysin onnistumiseen Ehjä vatsakalvo joka toimii filtterinä dialyysille Intraperitoneaaliset absessit Kiinnikkeet Tuore laparotomia Pallearuptuura Toimiva PD-katetri (väliaikainen tai pysyvä) Välineet Nesteet, letkut, filtraatti pussi

19 Peritoneaali dialyysi - komplikaatiot Peritoniitti Katetri infektiot Vuoto Suoliperforaatio Katetri ongelmat: Tukokset, kipu, virtaus ongelmat,

20 Peritoneaalidialyysi annostus Dialyysi volyymi ml/kg tai ml / m 2 BSA Esim: Tunnin kierto: Sisään 5min - vatsaontelossa 40min - ulos valutus 15min

21 CRRT Soveltuu kaiken ikäisille Tosin mitä pienempi lapsi sitä enemmän ongelmia dialyysireitin kanssa Vaatii kätännössä aina antikoagulaation (sitraatti, hepariini, epoprostenoli/pgi-2, LMWH) Monimutkaisempi laitteisto Helposti yhdistettävissä ECMO kiertoon

22 Munuaiskorvaus hoitojen syyt ORIGINAL ARTICLES Table II. Differences in survival depending on primary diagnosis Primary diagnosis Number/total (% of cohort) Survive Non-survivors Survival versus non-survival P value Sepsis 25/84 (30%) 9/25 (36%) 16/25 (64%).37 Cardiac disease 16/84 (19%) 6/16 (38%) 10/16 (62%).59 Inborn error of metabolism 13/84 (15%) 8/13 (62%) 5/13 (38%).15 Hepatic 9/84 (11%) 0/9 (0%) 9/9 (100%) <.01 Oncology* 6/84 (7%) 3/6 (50%) 3/6 (50%).73 Primary pulmonary 5/84 (6%) 3/5 (60%) 2/5 (40%).44 Renal 5/84 (6%) 4/5 (80%) 1/5 (20%).09 Other z 5/84 (6%) 3/5 (75%) 2/5 (40%).19 *3 neuroblastoma, 2 acute lymphocytic leukemia, 1 hemophagocytic syndrome. Autosomal recessive polycystic kidney disease, cortical necrosis, unknown cause of chronic kidney disease, renal agenesis, congenital nephrotic syndrome. z2 nephrotoxin, 1 congenital diaphrmatic hernia, 1 Omenn s syndrome, status post bone marrow transplant, 1 censored. Askenazi)DJ)et)al.)Con1nuous)Renal)Replacement)Therapy)for)Children)#10)kg:)A)Report)from)the)Prospec1ve)Pediatric) Con1nuous)Renal)Replacement)Therapy)Registry.)J"Pediatr"2012.") )

23 CRRT aloitus 1. Dialyysikanyyli 2. Filtteri 3. Antikoagulaatio 4. Dialyysikoneen säädöt / dialyysi annos 5. Ravitsemus 6. Priming (veri / kirkas / albumiini)

24 Hemodialyysikanyyli Paino Väliaikainen katetri 2 6 kg Fr 6 15 kg 8 Fr kg 9 10 Fr > 30 kg Fr Paino Tunneloitu katetri kg Väliaikainen katetri 8 15 kg Medicomp 8 Fr kg Medicomp 8 tai 12.5 Fr kg Medicomp 12.5 Fr > 40 kg Palindrome 14.5 Fr

25 Hemodialyysikanyyli Katetrin koko ja sijainti vaikuttaa kelan ikään Hackbarth R et al. The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: A report from the PPCRRT registry. Int J Artif Organs 2007; 30(12):

26 Dialyysiannos / modaliteetti CVVH, CVVHD, CVVHDF, SCUF Kaikki modaliteetit mahdollisia lapsilla Dialyysi annos ml/h/1.73 m 2 Koneeseen säädettävä n. 10% suurempi annos kuin tavoitellaan, dialyysikoneen downtimen takia

27 Septinen AKI ja CRRT CRRT:llä mahdollisesti immunomoduloiva vaikutus Puhdistaa inflammaatio mediaattoreita korkeilla annoksilla Munuais annos = 20-30ml/kg/h Sytokiini annos = (-100) ml/kg/h Toisaalta puhdistaa myös antibiootteja, hivenaineita, aminohappoja, yms

28 High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis specifically described; RESEARCH however, it was noted that three 1.5 to 33.9 hours) [26]. Open Access patients in the HVHF group and one in the SVHF had hypothermia, High-volume defined as a core temperature hemofiltration <34 C while Discussion for septic acute kidney receiving CRRT [28]. Associated with this, core temperature A systematic search of the literature for randomized was significantly injury: lower the a systematic HVHF compared with review SVHF controlled and meta-analysis trials evaluating HVHF, according to the Pardubice definition [29], compared with SVHF as adjuvant group (37.2 C versus 37.9 C; P <0.001).Theauthorsalsodescribed that hypophosphatemia Edward Clark 1,2, Amberoccurred O Molnar 1,2 more, Oliviercommonly Joannes-Boyau 3, therapy Patrick M Honoré for sepsis 4, Lindsey andsikora septic 5 AKI, found only four eligible studies for analysis. The quality of each study in- and Sean M Bagshaw among HVHF-treated patients (65%) 6* compared with SVHF (54%); Abstract however, hypophosphatemia was not specifically cluded in our review was reasonable, considering the defined [28]. 4 tutkimusta joissa verrattu matala vs korkea annoksista ( > 50ml/kg/h) Abstract inherent challenges for blinding an extracorporeal therapy. Introduction: The study hemodialyysia byhigh-volume Introduction: Joannes-Boyau hemofiltration High-volume et al. hemofiltration [26] reported (HVHF) is (HVHF) three an attractive is an attractive therapy Our therapy for review for the the treatment found treatment of septic that of acute HVHF, septic kidney compared acute kidney with adverse injury (AKI). events Small injury (one experimental (AKI). acute Smallembolic experimental and stroke, uncontrolled and one myocardial studies have SVHF, suggested hadhemodynamic nohemodynamic significant and survival impact and benefits survival on at short-term benefitsmortal- at higher infarction, doses N = 470, of higher and HVHF doses Kaikilla one than of episode HVHF those septinen than of used those major for used sokki, the postoperative for the high-intensity ainoastaan ity, arms aikuisia, kidney of the of the RENAL recovery, ei RENAL and sydänkirurgiaa ATNand improvement studies. ATNOur studies. aim was in hemodynamic Our to aim was topro- evaluate the effects of high-volume with standard-volume hemofiltration (SVHF) bleeding). evaluate the One effects major of high-volume adverse event hemofiltration occurred in(hvhf) the compared file, or reduction with standard-volume in ICU or hospital hemofiltration length-of-stay. (SVHF) In a for septic AKI. for septic AKI. Edward Clark 1,2, Amber O Molnar 1,2, Olivier Joannes-Boyau 3, Patrick M Honoré 4, Lindsey Sikora 5 and Sean M Bagshaw 6* Outcome: 28-päivän mortaliteetti Methods: A systematic review and meta-analysis of publications between 1966 and 2013 was performed. The review was limited to randomized-controlled trials that compared HVHF (effluent rate greater than 50 ml/kg per hour) versus SVHF in the treatment of sepsis and septic shock. The primary outcome assessed was 28-day mortality. Other outcomes assessed were recovery of kidney function, lengths of ICU and hospital stays, vasopressor dose reduction, and adverse events. Methods: A systematic review and meta-analysis of publications between 1966 and 2013 was performed. The review was limited to randomized-controlled trials that compared HVHF (effluent rate greater than 50 ml/kg per hour) versus SVHF in the treatment of sepsis and septic shock. The primary outcome assessed was 28-day mortality. Other outcomes assessed were recovery of kidney function, lengths of ICU and hospital stays, vasopressor dose reduction, and adverse events. Results: Four trials, including 470 total participants, were included. Pooled analysis for 28-day mortality did not show any meaningful difference between HVHF compared with SVHF (OR, 0.76; 95% CI, 0.45 to 1.29). No included studies reported statistically significant differences between groups for any of the secondary outcomes. Adverse events, including hypophosphatemia and hypokalemia, were more commonly observed in HVHF-treated patients, although reporting was inconsistent across studies. Results: Four trials, including 470 total participants, were included. Pooled analysis for 28-day mortality did not show any meaningful difference between HVHF compared with SVHF (OR, 0.76; 95% CI, 0.45 to 1.29). No included studies reported Conclusions: statistically Insufficient significant evidence exists differences of a therapeutic between benefit groups for routinefor use of any HVHF offor the septic secondary AKI, other than outcomes. on Adverse an experimental basis. Given the logistic challenges related to patient recruitment along with an incomplete events, Figure 2including Forest plot for odds of 28-day mortality. understanding hypophosphatemia of the biologic mechanisms and hypokalemia, by which HVHFwere may modify more outcomes, commonly further observed trials should focus in HVHF-treated on patients, although reporting alternative wasextracorporeal inconsistent therapies across as an studies. adjuvant therapy for septic AKI rather than HVHF. Conclusions: Insufficient evidence exists of a therapeutic benefit for routine use of HVHF for septic AKI, other than on an experimental basis. Given the logistic challenges related to patient recruitment along with an incomplete understanding of the biologic mechanisms by which HVHF may modify outcomes, further trials should focus on alternative extracorporeal therapies as an adjuvant therapy for septic AKI rather than HVHF. Introduction Sepsis is a common cause of critical illness and the leading cause of death for patients admitted to the intensive care unit (ICU) [1]. It has been theorized that the removal of inflammatory mediators and/or bacterial toxins from the bloodstream could result in a beneficial downregulation of The definition of what constitutes high volume in HVHF remains unclear [6,7]. Based on the results of two large randomized-controlled trials (RCTs) [8,9] and subsequent systematic reviews [10,11], the adequate dose of hemofiltration treatment for acute kidney injury (AKI) (that is, the renal dose) has been defined as an effluent

29 Dialyysiannos / antikoagulaatio lasta vuosilta Yhdysvalloista Kaikki alle 10kg painoisia Sitraatti 55%, hepariini 45% Table VII. CRRT circuit data in children #10 kg 5 kg (N = 170) >5 kg (N = 251) P value Anticoagulation protocol <0.001 Citrate 76 (45%) 155 (62%) Heparin 94 (55%) 96 (38%) Prime <0.001 Blood 164 (96.5%) 202 (80%) Saline 5 (3%) 29 (12%) Albumin 1 (0.5%) 20 (8%) Parameter Blood flow* (ml/kg/min) 12 ( ) 6.6 ( ) <0.001 Daily effluent volume* 3328 ( ) 2321 ( ) <0.001 (ml/h/1.73 m 2 ) Circuit life 28 (11-67) 37 (16-67) 0.15 *Median (IQR). who were unable to achieve dry weight after CRRT initiation had higher mortality. FO has been shown to be associated with mortality in critically for Children ill children #10 and kg: adults. A Report 3,12-18 from Wethe provide Prospective data suggesting Pediatric Askenazi DJ et al. Continuous Renal Replacement Therapy Continuous Renal Replacement that Therapy theseregistry. effects are J Pediatr applicable to small children. After controlling for PRISM 2, FO, P aw, urine output at CRRT, and Sy 5 t sim ica wi am tio ate of an tho str co ho im suc an thi var tw

30 Mikä modaliteetti on paras? Kaikilla modaliteeteilla edut ja haitat Punnittava potilaskohtaisesti Huomioitava Nesteen poisto Clearance / Dysequilibrium Elektrolyytti tasapaino Lapsen hemodynamiikka Infektio status

31 The GOOD: CRRT Good Tehokas Helposti kontrolloitavissa Fysiologinen Hemodynaamisesti epävakaalle paras vaihtoehto Ei kontraindikaatioita Bad Kallis Vaatii henkilökunnan koulutuksen Katetri infektiot Ugly Dysequilibrium riski Antikoagulaatio

32 The Bad: ihd Bad Työläs ja kallis Good Erittäin tehokas Hemodynaamisesti vaativa Vuorokauden nesteenpoisto 2-4h aikana! Ugly Dysequilibrium riski

33 The Ugly: PD Good Halpa Melko nopeasti toteutettava Yksinkertainen Sopii myös epävakaalle hemodynamiikalle Bad Huono puhdistuma Kontraindikaatiot Ugly Nesteenpoisto huonosti kontrolloitavissa Peritoniitti riski