Hisar Intercontinental Hospital

Brain Protection in Pediatric Aortic Arch

Repair: Deep Hypothermic

Circulatory Arrest, Selective Cerebral

Perfusion or Combined Technique

No Disclosures

DHCA has been widely employed DHCA has been widely employed since 1970s in complex CHD in since 1970s in complex CHD in neonatesneonatesReduction in CPB time Elimination of the need for multiple

cannulaeBloodless operative field

History of DHCAHistory of DHCA

First SCP for arch replacement First SCP for arch replacement DeBakey at al 1962

SCP from axilllary artery SCP from axilllary artery Panday et al 1974Panday et al 1974

Hypothermic (25-28C) SCPHypothermic (25-28C) SCPFirst et al 1986First et al 1986

Early successful hypothermic SCPEarly successful hypothermic SCPMatsuda et al 1989Matsuda et al 1989Kazui et al 1989 Kazui et al 1989

First SCP for aortic arch repair in First SCP for aortic arch repair in neonates neonates Asou et al 1996Asou et al 1996

History of SCP for History of SCP for AdultsAdults

The circle of Willis (CoW)The circle of Willis (CoW)%17 incomplete CoW %17 incomplete CoW 11

Collateral vessels 2

Ophthalmic arteryLeptomeningeal vesselsExternal carotid artery

Anatomy Anatomy

1. Merkkola et al. Ann Thorac surg;2006:82:74.2. Eur J Cardiothorac Surg 2010:37:1332

Pathophysiology of Pathophysiology of Neonatal Brain InjuryNeonatal Brain Injury

The brain utilizes up to 20% of The brain utilizes up to 20% of total body Ototal body O22 consumption consumption

Mechanisms of Cell Death Necrosis Apoptosis

DHCA Excitatory amino acids: glutamateExcitatory amino acids: glutamate

Selective Vulnerability of the Developing Brain (DHCA)

Adult : generalized Jacksonian type seizures

Neonatal: focal seizures Infant: choreoathetosis

Motor and Cognitive Outcomes After Surgery

for CHD NNeonateseonates and young infantsand young infants have have

greatest risk for brain injurygreatest risk for brain injury Duration of DHCADuration of DHCA Seemingly normal 1-year-old after Seemingly normal 1-year-old after

surgerysurgery Significant abnormalities of Significant abnormalities of

neurodevelopment at 4 or 8 years of neurodevelopment at 4 or 8 years of agesages

Neonatal Brain Protection

Hypothermia Hypothermia pH stat blood management pH stat blood management Pharmacologic agents Pharmacologic agents

Volatile anaesthetics Volatile anaesthetics Thiopental Thiopental SteroidsSteroids

TechniquesTechniques DHCADHCA Intermittent cerebral perfusionIntermittent cerebral perfusion SCPSCP

Hypothermia

EEG silence and EEG silence and disappearance of the disappearance of the SSER occur at 17°CSSER occur at 17°C

Deep brain cools faster than the Deep brain cools faster than the subcortical areassubcortical areas

2°C-to 3°C between deep brain and 2°C-to 3°C between deep brain and superficial brain superficial brain

Blood temperature should not exceed Blood temperature should not exceed 37°C during rewarming 37°C during rewarming

Arterial Blood Gas Management

pH Stat & Alpha Stat The impact of The impact of arterial blood gas arterial blood gas

management duringmanagement during DHCA in children DHCA in children is still unclearis still unclear

pH statpH stat improveimprovess cerebral blood flow cerebral blood flow and cerebraland cerebral

ooxygenationxygenation and effectively cools the brain and effectively cools the brain but has a greater risk of microembolismbut has a greater risk of microembolism

Experimental Experimental studies suggestedstudies suggested that that pHpH stat arterial blood gas stat arterial blood gas management provides improvedmanagement provides improved brain brain protection during DHCA. protection during DHCA.

However, clinical studies have shown However, clinical studies have shown no significant differance in the no significant differance in the longterm results between the pH stat longterm results between the pH stat and the alpha stat and the alpha stat

Pharmacologic Agents Pharmacologic Agents

Methylprednisolone* Barbiturates Volatile anesthetics

Lidocain MannitolMannitol AnticonvulsantsAnticonvulsants Benzodiazepines PropofolPropofol Aprotinin Ca++ channel blockers Leukocyte filtration Diazoxide Thromboxane A2 blokers Glutamate Receptor Glutamate Receptor

BlockersBlockers Nitric Oxide Synthase Nitric Oxide Synthase

InhibitorsInhibitors Free Radical ScavengersFree Radical Scavengers

Techniques1-DHCA

The advanteges of DHCA includes the The advanteges of DHCA includes the reduction ofreduction of

Cellular metabolic rate Cellular metabolic rate Vascular permeabilityVascular permeability Blood-brain barrier disruption Blood-brain barrier disruption Postischemic cerebral edema Postischemic cerebral edema

Disadventages of DHCADisadventages of DHCA Longer myocardial ischemia Longer myocardial ischemia Autoregulation is lost (below 22°C)Autoregulation is lost (below 22°C)

Coagulative, renal and pulmonary Coagulative, renal and pulmonary complicationscomplications

NNeurodevelopmental morbiditieseurodevelopmental morbidities

Techniques1-DHCA

Neurologic sequelae depends onNeurologic sequelae depends on Arrest periodArrest period Variations in perfusion technique during Variations in perfusion technique during

cooling and rewarming cooling and rewarming Safe DHCA period Safe DHCA period

35<min35<min Beyond this period neurologic Beyond this period neurologic

sequelae may increase sequelae may increase Late neurologic abnormal Late neurologic abnormal

develepment develepment

1. Oates, et al. J Thorac Cardiovasc Surg. 1995;110:7862. Newburger et al. N Engl J Med. 1993;329:10573. Bellinger et al. Circulation. 1999;100:526

Techniques2-Intermittent Cerebral

Perfusion ICP has been used routinly in ICP has been used routinly in

pulmonary thromboendarterectomy pulmonary thromboendarterectomy for adult patientsfor adult patients

Experimental studies Experimental studies 1,21,2 using neonatal using neonatal piglets have shown that ICP has better piglets have shown that ICP has better brain protection than DHCA brain protection than DHCA

However, there is not an adequate However, there is not an adequate clinical study supporting the clinical study supporting the advantages of ICP in pediatric advantages of ICP in pediatric patients .patients .

1. Kimura T, et al. Demmy TL, et al. JCS 1994;108:6582. Langley SM, et al. Ann Thorac Surg 1999;68:4

Techniques3-Selective elective CCerebral erebral

PPerfusion erfusion Technical issues relating toTechnical issues relating to SCP, SCP, such such

as theas the perfusate temperatureperfusate temperature,, the flow the flow raterate,, and pressure and pressure , are still unsolved , are still unsolved

Lowering perfusion pressure gradually from Lowering perfusion pressure gradually from 90 mmHg to 40 mm Hg 90 mmHg to 40 mm Hg doesdoes not change not change cerebral blood flow orcerebral blood flow or CMROCMRO22 (1)(1)

BBelow 40 mmelow 40 mm Hg, cerebral blood flow Hg, cerebral blood flow declinedecliness abruptly abruptly 11

AA reduction of 45% reduction of 45% to 70% in pump flow at to 70% in pump flow at 18°C significantly reduce18°C significantly reduces s cerebral blood cerebral blood flow and CMROflow and CMRO22 (2)(2)

1. Tanaka , et al. J Thorac Cardiovasc Surg 1988;95:124 2. Kern , et al. Ann Thorac Surg 1993;56:1366

Which one ? DHCA or SCP

Some surgeons have moved away Some surgeons have moved away from DHCAfrom DHCA

There are many risksThere are many risks

Some surgeons Some surgeons still prefer DHCA prefer DHCA becausebecause

The neurodevelopmental outcomes are The neurodevelopmental outcomes are not different ! not different !

TTechnical surgical reconstruction can beechnical surgical reconstruction can be performed with greater precisionperformed with greater precision than than by using SCPby using SCP

The differences between DHCA & SCP

In a piglet model, In a piglet model, SCP SCP was found superior was found superior toto DHCADHCA11

The The resultsresults from from clinical studies clinical studies comparing comparing SSCP with DHCA haveCP with DHCA have not shown not shown a similar benefita similar benefit

A A random trial demonstrated no clearrandom trial demonstrated no clear difference difference between between SCPSCP and DHCA and DHCA after after 1 year 1 year of of Norwood Norwood surgerysurgery 22

Two additional clinical studies also Two additional clinical studies also demonstrated no cleardemonstrated no clear differencedifferencess between between SSCP CP and DHCAand DHCA 3,43,4

Neurodevelopmental outcomes after 1 Neurodevelopmental outcomes after 1 yearyear of of Norwood Norwood operationsoperations with with SCPSCP werewere significantlysignificantly below population norms below population norms 2,42,41. Myung, et al. J Thorac Cardiovasc Surg. 2004;127:1051

2. Goldberg, et al. J Thorac Cardiovasc Surg. 2007;133:8803. Dent, et al. J Thorac Cardiovasc Surg. 2006;131:1904. Visconti ,et al. Ann Thorac Surg. 2006;82:2207

Neurodevelopmental Neurodevelopmental Outcomes After Regional Outcomes After Regional

Cerebral PerfusionCerebral Perfusion

MRI Brain Injury Preoperative,

Postoperative and Premature 20-40 % preoperative MRI brain 20-40 % preoperative MRI brain

injury injury 11

35-75 % postoperative MRI brain 35-75 % postoperative MRI brain injuryinjury 1 1

Brain injury in premature newborns Brain injury in premature newborns detected with MRI is 37 %detected with MRI is 37 % 2 2

1. Andropoulos, et al. Ann Thorac Surg 2013;95:6482. Miller, et al J Pediatr 2005;147:609

RReconstructioneconstruction of A of Aortic ortic AArch and rch and Isthmus

Hypoplasia in Our Clinic BB

etween Jan 2007 etween Jan 2007 -- Sep 2012 Sep 201233

7 cases with aortic arch and 7 cases with aortic arch and isthmus hypoplasia accompanisthmus hypoplasia accompaning ing other other cardiac defects cardiac defects

This technique was not used in technique was not used in patients who had patients who had HLHSHLHS

Additional Additional PProcedures rocedures

Patients (n)

VSD 23

Interruption repair 3

Subaortic resection 2

Arterial switch operation 8

CAVSD repair 2

Pulmonary arterial banding 3

Septectomy 1

Cardiopulmonary bypass time, min 154±61

Cross-clamp time, min 64.7±36

Selective cerebral and myocardial perfusion time, min

22.4±8

Descending aorta ischemia time, min 26.1±6.7

Total circulatory arrest time, min 7.1±2.7 (minimum: 4, maximum: 10)

Extubation time, hour 159±180

Length of ICU stay time, hour 219± 249

Hospital length of stay time, day 13±11

Postoperative CoursePostoperative Course

All VSD-CoAAH patients were extubated within 1. POD

Prolonged extubation patients had single ventricle physiology or complex cardiac anomalies

None of the patients had neurological defects

Perfusion Techniques in Neonatal Arch Reconstruction

Ohne RG. J Thorac Cardiovasc Surg 2009;137:803

1. Result 1. Result

SCP is theoreticalSCP is theoreticallyly advantageous advantageous inin preventpreventinging ischemia of the brain ischemia of the brain

It should not be relied on totally as a It should not be relied on totally as a safe method safe method

AAn inapn inapppropriately applied ropriately applied SCPSCP may may cause more damage than cause more damage than TCATCA

High or High or low low flow and pressure during flow and pressure during SCPSCP may cause brain damage.may cause brain damage.

Surgical Surgical procedureproceduress may take may take a a longer longer timetime when performed with when performed with SCP SCP

2. Result 2. Result

NeuromonitorizationNeuromonitorization is highly necessary is highly necessary during SCP compared to TCAduring SCP compared to TCA

We know that short term We know that short term TCATCA is a safe is a safe methodmethod

The The SCPSCP technique technique doesndoesn’’t effect thet effect the surgeon's comfort and speedsurgeon's comfort and speed

In our clinical experiance combining In our clinical experiance combining SCP and shortSCP and short period of period of TTCCA (under 10 A (under 10 minutes) minutes) isis safe and practical in safe and practical in pediatric pediatric aortic aortic arch arch reconstructioreconstructionn

Thank You!