5/19/20

Brain&Kidney 2 0 2 0

CHRONIC KIDNEY DISEASE IN THE NEUROLOGICAL ICU

Sara Stern-Nezer, MD,MPHAssistant HS Professor University of California, IrvineDepartments of Neurology & Neurosurgery

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Brain&Kidney 2 0 2 0Disclosures

• I like taking care of acute neurologically ill patients

• I have no financial disclosures

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Chronic disease in the ICU?

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Overview

• CKD increases likelihood of admission to neuroICU

• CKD complicates management of acute neurological disease

• CKD affects outcome while admitted and after discharge

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CKD increases risk of admission to neurological ICU

Increased risk of stroke beyond traditional cardiovascular risk factors

Chen et al, PLOS (2012) 7;4

CKD as an independent risk factor

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Proteinuria and increased risk of stroke

Kelly & Rothwell, Int J Stroke (2020); 15(1):29-38

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Wang et al, AJKD (2014);63(4):604-611

HD-hemodialysisPD-peritoneal dialysis RC-referencecohort

HS-hemorrhagic stroke IS-ischemicstroke

Incident ischemic stroke risk and CKD

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Wang et al, AJKD (2014);63(4):604-611

HD-hemodialysisPD-peritoneal dialysis RC-referencecohort

HS-hemorrhagic stroke IS-ischemicstroke

Incident hemorrhagic stroke risk and CKD

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CKD increases risk of admission to neurological ICU

Increased risk of stroke beyond traditional cardiovascular risk factors

Increased risk of bleedingDO NOT COPY

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Hemorrhagic complications in patients with CKDHemorrhagic pancreatitisGIbleedingIntracranial hemorrhagesHemorrhagic pleural effusionsRetroperitoneal bleedingSubcapsular liver hematomaOcularhemorrhagesUterine bleedingSurgical bleeding

Moinar at al, JASN (2016);27(9):2825-2832Boccado et al, Semin Thromb Hemost (2004);30(5):579-89

Major hemorrhagic events more

likely inpatients with CKD

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Platelet abnormalities

Abnormal platelet-vessel wall interactions

Anemia

Moinar at al, JASN (2016);27(9):2825-2832Boccado et al, Semin Thromb Hemost(2004);30(5):579-89

Factors involved in pathogenesis of CKD-associated bleeding

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High grade CKD increases risk of ICH

13Molshatski et al, Cerebrovasc Dis (2011);31:261-277

p=0.009

Hematoma volumes larger with moderate to severeCKD

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Molshatski et al, Cerebrovasc Dis (2011);31:261-277

p=0.02

More likely to be lobar

15Molshatski et al, Cerebrovasc Dis (2011);31:261-277

p=0.08

Intraventricular expansion more common

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Treatment of uremic

bleeding

Hedges et al. Nat ClinPract Nephrol (2007);3(3):138-53

Hemodynamically unstable

Emergency surgery

Urgentsurgery

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Treatment of uremic

bleeding

• DDAVP

Hedges et al. NatClinPract Nephrol (2007);3(3):138-53

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Treatment of uremic

bleeding

• DDAVP• Hemodialysis or peritoneal

dialysis

Hedges et al. Nat ClinPract Nephrol (2007);3(3):138-53

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Treatment of uremic

bleeding

• DDAVP• Dialysis• Cryoprecipitate

Hedges et al. NatClinPract Nephrol (2007);3(3):138-53

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Treatment of uremic

bleeding

• DDAVP• Dialysis• Cryoprecipitate• Estrogen

Hedges et al. Nat ClinPract Nephrol (2007);3(3):138-53

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Treatment of uremic

bleeding

• DDAVP• Dialysis• Cryoprecipitate• Estrogen• Recombinant EPO or blood

transfusion

Hedges et al. NatClinPract Nephrol (2007);3(3):138-53

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CKD increases risk of admission to neurological ICU

Increased risk of stroke beyond traditional cardiovascular risk factors

Increased risk of bleeding

Kidney disease associated with increased risk of subarachnoid hemorrhage

Intracranial Aneurysms More Prevalent inPolycystic Kidney Disease Patients• Autosomal dominant polycystic kidney

disease is common affecting 1 in 1000 people

• High risk of intracranial aneurysm andSAH

• Estimated at 10-20% of PKD patients will have intracranial aneurysm

• Prevalence rate of SAH 6.9 compared to1.7 for patients with just atherosclerosis and 3.4 with family history

Niemczyk et al, Brain (2013); 59(6):1556-1559; Cagnazzo et al Acta Neurochir (2017);159(5):811-821; Vlak et al, Lancet Neurol (2011); 10(7): 626-36

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Ankit Sakhuja. Stroke. (2013);45(1)71-76

SAH HIGHERIN PATIENTSON DIALYSIS

Adjusted

Notadjusted

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CKD increases risk of admission to neurological ICU

Increased risk of stroke beyond traditional cardiovascular risk factors

Increased risk of bleeding

Kidney disease associated with increased risk of subarachnoid hemorrhage

Nutrient imbalances are common in CKD patients

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Hung et al. Am J Kidney Dis (2001);38(5):941-947

* p<0.005** p<0.001

Thiamine Deficiency important cause of unexplained encephalopathy in dialysis patients

• Thiamine deficiency associated withWernicke’s Syndrome

• Triad of• Confusion• cerebellar ataxia• abnormal eye movements

(opthalmoplegia)• Important reversible cause of

unexplained altered mental status in ESRD patients in the ICU

27Hung et al. Am J Kidney Dis (2001);38(5):941-947

* p<0.005** p<0.001

90% ofpatientshadsignificantimprovement inneurologicaldeficits withthiaminedeficiency

Thiamine Deficiency important cause of unexplained encephalopathy in dialysis patients

• Thiamine deficiency associated withWernicke’s Syndrome

• Triad of• Confusion• cerebellar ataxia• abnormal eye movements

(opthalmoplegia)• Important reversible cause of

unexplained altered mental status in ESRD patients in the ICU

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KD complicates managementf acute neurological disease

Increased risk of infection

Immune dysfunction in uremia involves innate and adaptive immunity

Kato et al, Clin J Am Soc Nephrol (2008);3:1526-1

Innate   immunity

Disturbance

PAMFsignaling

Dysregulated

Monocytes Hyporeactive

Neutrophils Decreased bactericidal abilities

Cytokines IncreasedlevelsComplement Abnormal activation

Adaptive immunity Disturbance

T lymphocytes Impaired activation Increased Th1/Th2 ratio

B lymphocytes Decreased cell countAntigen presenting cells

Functionaltered

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Kato et al, Clin J Am Soc Nephrol (2008);3:1526-1522

Sepsis is a major causeof

death in patients with

ESRD

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KD complicates managementf acute neurological disease

Increased risk of infection

Interactions between injured brain and modality of dialysisDO NOT COPY

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Hemodialysis in acute brain injury can cause worsening cerebraledema

Pre-hemodialysis

PostPost--hemhemodiodialalysiysiss

Kumar et al. Neurocrit Care (2015); 22(2):283-287

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Hemodialysis in acute brain injury can cause worsening cerebral edema

Pre-hemodialysis

Post-hemodialysis

Kumar et al. Neurocrit Care (2015); 22(2): 283-287

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Worsening cerebral perfusion pressure can occur with any hypotension during dialysis

Osgood et al. Chest. (2017_;152(6)1009-11Hirsch & Josephson. Adv Chron Kid Dis (2013);20(1):39-44

Study ofpatients withhepatic encephalopathy

found intermittent hemodialysis caused increase ICP 60% and

decrease CPP

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Worsening cerebral perfusion pressure can occur with any hypotension during dialysis

Osgood et al. Chest. (2017_;152(6)1009-11Hirsch & Josephson. AdvChronKidDis (2013);20(1):39-44

Loss of autoregulation in

injuredbrain

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KD complicates managementf acute neurological disease

Increased risk of infection

Interactions between brain perfusion and modality of dialysis

Medication dosing and clearance

CKD requires extra attention to medication dosing

Nguyen.Nephrology (2010); 35(3): HS16-21

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CKD requires extra attention to medication selection & clearance

• Careful attention in ICU to choice of opioids used

• Midazolamclearance reduced and half-life doubled in renal failure patients

• Sedation clearanceconsideration important when asked for neuro-prognostication

Vinik et al. Anesthesiology (1982);59(5):390-4 Lea-Henry et al. CJASN (2018);13(7):1085-95

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KD complicates managementf acute neurological disease

Increased risk of infection

Interactions between brain perfusion and modality of dialysis

Medication dosing and clearance

Selection and maintenance of hyperosmolar agents to treat ICP

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Hyperosmolar therapy requiresspecial consideration inCKD

• Mannitol historically avoided• Contraindicated in anuria

• Hypertonic saline largely safe and effective based on numerous studies although monitoring required

• Monitor volumestatus

• Monitor sodium and avoid rapid correction if dialysis ongoing

Corry et al. World J Crit Care Med (2014); 3(2):61-67 Froelich et al. Crit Care Med (2009);37(4):1433-41 Hirsch et al. Neuro Crit Care (2012);17(3):388-394

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CKD affects outcome

CKD associated with longer ICU length of stayDO NOT COPY

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CKD AND LENGTH OF STAY

Ngu et al. Intern Med J (2017);47(1):62-67

Hospital length of stay 14 (8-23) 9 (6-17). p <0.01

CKD Non-CKD

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CKD affects outcome

CKD associated with longer ICU length of stay

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CKD & MORTALITY

Ngu et al. Intern Med J (2017);47(1):62-67

Death 5.12% 1.35% p<0.01

CKD Non-CKD

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CKD affects outcome

CKD associated with longer ICU length of stay

Independently associated with increased mortality

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HIGHCOST OF

CKD & STROKE

Dad et al, Semin Nephrol. (2015);35(4):311-

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• Chronic kidney disease patients frequently have comorbidities that increase their likelihood of admission to the ICU and disease severity

• Coagulopathy should be considered in medical decisions

• CKD alters management and requires special considerations

• Optimum therapies for patients with acute brain injury and CKD require ongoing research and attention

In summary

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Thank you!!

• Email ssternne@hs.uci.edu• Thank you to Dr. Lau and Dr. Fisher for the opportunity to

speak today

Brain&Kidney 2 0 2 0

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