Deep Hypothermic Circulatory Arrest in Pediatric Cardiac Surgery

2009

Nabila Fahmy, MDNabila Fahmy, MD

Professor of Professor of AnesthesiologyAnesthesiology

Ain Shams UniversityAin Shams UniversityZukass2001@yahoo.com

• Cessation of the blood circulation for some time during surgery of the arch and repair of congenital heart defects is normally required to allow a bloodless operation field..

• Hypothermia is the most important mechanism for end-organ protection, particularly the brain, during such operations.

• Cardiopulmonary bypass is used for core cooling before deep hypothermic circulatory arrest (DHCA) is initiated .

WHAT IS DHCA?WHAT IS DHCA?

DEEP HYPOTHERMIC DEEP HYPOTHERMIC CIRCULATORY ARREST (DHCA)CIRCULATORY ARREST (DHCA)• Mild hypothermia – 30 C to 34 CMild hypothermia – 30 C to 34 C

Moderate hypothermia – 25 C to 30 CModerate hypothermia – 25 C to 30 C

Deep hypothermia – 15 C to 22 CDeep hypothermia – 15 C to 22 C

• Circulatory arrest – no flow in the blood vesselsCirculatory arrest – no flow in the blood vessels

• DHCA – no blood flow during deep hypothermiaDHCA – no blood flow during deep hypothermia

HOW DO WE DO HOW DO WE DO DHCA?DHCA?

TECHNIQUE OF DHCATECHNIQUE OF DHCA• Usually plannedUsually planned• Most protocols involving DHCA involve the following :Most protocols involving DHCA involve the following :

– Administration of barbiturates, usually thiopental for the reduction of Administration of barbiturates, usually thiopental for the reduction of cerebral metabolism.cerebral metabolism.

– Mannitol to help reduce potential increased intracranial pressure and to Mannitol to help reduce potential increased intracranial pressure and to reduce free radicals.reduce free radicals.

– Steroids to promote cell membrane integrity and reduce brain swelling.Steroids to promote cell membrane integrity and reduce brain swelling.– Cooling is started before CPB by simply cooling the operating room and Cooling is started before CPB by simply cooling the operating room and

with ice packing to the head with ice packing to the head After systemic heparinization and After systemic heparinization and cannulation are performed, CPB is started and cooling is begins for at cannulation are performed, CPB is started and cooling is begins for at least 20-30 minutes. The patient's body temperature is monitored by least 20-30 minutes. The patient's body temperature is monitored by means of esophageal, tympanic, and rectal routes. After adequate means of esophageal, tympanic, and rectal routes. After adequate cooling is achieved, the circulation is arrested to allow the surgeon to cooling is achieved, the circulation is arrested to allow the surgeon to perform the critical part of the reconstruction. The duration of DHCA is perform the critical part of the reconstruction. The duration of DHCA is limited to the shortest time possible. After circulation is restarted, the limited to the shortest time possible. After circulation is restarted, the rest of the repair is performed during the rewarming phase.rest of the repair is performed during the rewarming phase.

– The anesthetic and surgical plan involves mutual goals of tissue and The anesthetic and surgical plan involves mutual goals of tissue and organ protection by decreasing cellular metabolism and substrate organ protection by decreasing cellular metabolism and substrate delivery during the absence of perfusion.delivery during the absence of perfusion.

WHY DHCA?WHY DHCA?

ADVANTAGES OF DHCAADVANTAGES OF DHCA• Bloodless operating field with improved exposureBloodless operating field with improved exposure• Decreased exposure to cardiopulmonary bypass with its Decreased exposure to cardiopulmonary bypass with its

sequelae (such as activation of white cells and endothelium, sequelae (such as activation of white cells and endothelium, activation of cascades, consumption of coagulation factors activation of cascades, consumption of coagulation factors and platelets, hemolysis, etc.)and platelets, hemolysis, etc.)

• Diminished risk of embolism (solids and gases)Diminished risk of embolism (solids and gases)• No cannulas in the operating fieldNo cannulas in the operating field• Less distortion of heart - cannulas are not in placeLess distortion of heart - cannulas are not in place• DHCA offers brain protection for a period of about 30-60 DHCA offers brain protection for a period of about 30-60

minutes.minutes.• Reduced CMROReduced CMRO22 to be approximately 10%-15% of its to be approximately 10%-15% of its

normothermic base line.normothermic base line.• Lower plasma activated complement (C3a), interleukin 8, Lower plasma activated complement (C3a), interleukin 8,

interleukin 6 (when compared with low-flow CPB)interleukin 6 (when compared with low-flow CPB)

Bellinger DC, et al. N Engl J med. 1995;332:549-555

• The duration of DHCA is limited to the shortest time possible as (landmark boston circulatory arrest study, march 2007)– 3-5 mins of cerebral ischemia can be tolerated at 37 c.

– 15 mins 27 c.

– 41 mins 17 c.

0

0.2

0.4

0.6

0.8

1

1.2

0 3 5 10 15 30 45

Duration of total circulatory arrest (min)

Prob

abili

ty of

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circu

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ry

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st

37 c27 c17 c

CEREBRAL PHYSIOLOGY DURINGCARDIAC SURGERY

•CLINICAL STUDIES (Greeley, Kern, Ungerdeider) HAVE BEEN UNDERTAKEN IN THE LATE 1980s TRHOUGH MID 1990s TO UNDERSTANDNEUROPHYSIOLOGY IN INFANTS AND CHILDRENDURING CARDIAC SURGERY INVOLVING CPBAND DHCA•CNS HAS A HIGH METABOLIC NOTE & LIMITED ENERGY STORES •CNS IS THE MOST SENSITIVE ORGAN TO ISCHEMIA •ATTENTION HAS BEEN CENTERED ON NEUROLOGIC OUTCOME WHEN PERFUSION IS REDUCED, LEADING TO NEUROLOGIC COMPLICATIONS IN THE POSTOPERATIVE PERIOD.

THE REPORTED INCIDENCE OF NEUROLOGICAL COMPLICATIONSAFTER PEDIATRIC CARDIAC SURGERYRANGES FROM 2% TO 25%

Austin EH III,Edmonds HI,Auden SM et al.Benefit of neurophysiological monitoring for pediatricCardiac surgery.J Thorac Cardiovasc Surg 1997;114 :707-15

Menache CC,du Plessis AJ,Wessel DL et al.Current incidence of acute neurologic complicationsAfter open heart operation in childrenAnn Thorac Surg 2002; 73:1752.8

• Neurologic morbidity include– seizures

– stroke

– changed tone and mental status

– motor disorders -

– time to recovery of EEG activity .

– Abnormal cognitive function

– Post Pump choreoatherosis paraplegia

• Areas most vulnerable to ischemic Injury :– Neocortex

– Hippocompus– Striatum

mechanism of brain injury involves binding of glutamate to NMDA receptor , increasing the intracellular ca++ and subsequently activates proteases phospholipases and deoxyribonucleases , promotes the generation of free radicals cell injury , cell death .

Hypothermia the release of glutamate During DHCA , microemboli can be detected .

THE ETIOLOGY OF NEUROLOGICALDYSFUNCTION IN CHILDREN IS FOR THE MOSTPART ISCHEMIA

PATHOPHYSIOLOGIC MECHANISMS ACCOUNTINGFOR NEUROLOGIC INJURY INCLUDE: rate and extent of cooling and rewarming management of CPB prolonged DHCA anemia low cardiac output

http://content.nejm.org.ezp1.harvard.edu/content/vol332/issue9/images/large/01f2.jpeg

•UNDER DEEP HYPOTHERMIC CPB CBF IS REDUCED BUT THERE IS AN EXPONENTIALLY GREATER REDUCTION IN CMRO2. •A STATE OF LUXURY PERFUSION EXISTS WITH AN EXCESS OF FLOW RELATIVE TO OXYGEN CONSUMPTION; 1:75 (conferring cerebral protection)

•IN PATIENTS UNDERGOING DHCA CBF AND CMRO2 REMAIN DECREASED AFTER REWARMING AND WEANING FROM CPB

Sara Lozano, MD , Emad Mossad, MD – Journal of Cardiothoracic and Vascular Anesthesia. Volume 18, Issue 5, Pages 645-656 (October 2004)

IMPROVING IMPROVING NEUROLOGIC NEUROLOGIC

OUTCOMESOUTCOMES

BLOOD GAS MANAGEMENT (a-stat vs pH-stat) DURING CPB SIGNIFICANTLY AFFECTS CEREBRAL PHYSIOLOGY AN MAY HAVE AN IMPACT ON NEUROLOGICAL OUTCOME

Acid -- Base Management Acid -- Base Management

• Changes in cellular pH during hypothermia are mediated Changes in cellular pH during hypothermia are mediated through pcothrough pco22 homeostasis. homeostasis.

• When blood is cooled during cardiopulmonary bypass, pH When blood is cooled during cardiopulmonary bypass, pH becomes more alkaline.becomes more alkaline.

• pH-stat strategy – adding carbon dioxide - compensates for pH-stat strategy – adding carbon dioxide - compensates for this shift.this shift.

• This situation causes pH to increase as temperature This situation causes pH to increase as temperature decreases and electrochemical neutrality to be maintained.decreases and electrochemical neutrality to be maintained.

• Carbon dioxide is a potent cerebral vasodilator.Carbon dioxide is a potent cerebral vasodilator.

• αα-stat strategy – electrochemical neutrality is maintained by -stat strategy – electrochemical neutrality is maintained by keeping pH normal in temperature-uncorrected gases.keeping pH normal in temperature-uncorrected gases.

i.e,

αα-stat strategy – arterial blood measured at 37 C with -stat strategy – arterial blood measured at 37 C with pH of 7.40 and arterial pCO2 of 40 mm HgpH of 7.40 and arterial pCO2 of 40 mm Hg

(the hypothermic blood is alkalemic and (the hypothermic blood is alkalemic and hypocapneic)hypocapneic)

pH-stat strategy – hypothermic arterial blood at pH of pH-stat strategy – hypothermic arterial blood at pH of 7.40 and arterial pCO2 of 40 mm Hg7.40 and arterial pCO2 of 40 mm Hg

(blood at 37 C is acidemic and hypercapneic)(blood at 37 C is acidemic and hypercapneic)

28 oC

pH 7.56 pH 7.56 +CO2 pH 7.4

PaCO2 26 mmHg PaCO2 26 mmHg PaCO2 40 mmHg

Stat pH stat

pH 7.4 pH 7.26PaCO2 40 mmHg PaCO2 56 mmHg

lab 37oC

ADVANTAGES/DISADVANTAGESADVANTAGES/DISADVANTAGES

• αα-stat strategy: preserves autoregulation, optimizes -stat strategy: preserves autoregulation, optimizes cellular enzyme activity, but less metabolic cellular enzyme activity, but less metabolic suppressionsuppression

• pH-stat strategy: improves cerebral blood flow, pH-stat strategy: improves cerebral blood flow, cerebral oxygenation, and brain cooling efficiency cerebral oxygenation, and brain cooling efficiency during CPB, but greater risk of microembolism and during CPB, but greater risk of microembolism and free radical-mediated damagefree radical-mediated damage

Higher Hematocrit Improves Cerebral Outcome After Deep

Hypothermic Circulatory Arrest

Shin’oka T, Shum-Tim D, Jonas RA, Lidov HGW, Laussen PC, Miura T and du Plessis AShin’oka T, Shum-Tim D, Jonas RA, Lidov HGW, Laussen PC, Miura T and du Plessis A

Children’s Hospital Boston/Harvard Medical SchoolChildren’s Hospital Boston/Harvard Medical SchoolJ Thorac Cardiovasc Surg 1996;112:1610-21J Thorac Cardiovasc Surg 1996;112:1610-21

Extreme hemodilution (hematocrit < 10%) causes Extreme hemodilution (hematocrit < 10%) causes inadequate oxygen delivery during early cooling inadequate oxygen delivery during early cooling and higher hematocrit (30%) achieved with blood and higher hematocrit (30%) achieved with blood prime results in improved cerebral recovery after prime results in improved cerebral recovery after circulatory arrest.circulatory arrest.

Temperature Management

No difference between surface and core cooling. Provide adequate duration of cooling (> 20 min) before institution of DHCA. Avoid rapid cooling, avoid rapid rewarming and hyperthermia in postoperative period.

Sharma R, et al. Neurological evaluation and intelligence testing in the childwith operated congenital heart disease. Ann Thorac Surg 2000; 70: 575–581

Cottrell SM et al. Early postoperative body temperature and developmentaloutcome after open heart surgery in infants. Ann Thorac Surg 2004; 77: 66–71

Neuroprotective drugs

DrugDrug BasisBasis Current recommendations and Current recommendations and results of clinical trialsresults of clinical trials

Pre-operative use of

methyl prednisolone

Lesser inflammatory response

after CPB;

cerebral function recovers

earlier.

Intravenous methyl prednisolone

10 mg/kg administered 8 hours

and 2 hours prior to surgery in high

risk groups like neonates

Barbiturates Suppresses EEG activity; can

cause reduction

in high-energy phosphates

which is

detrimental after circulatory

arrest.

Not recommended prophylactically

Aprotinin Beneficial effect on recovery

of cerebral high

energy phosphates and

intracellular pH.

No clear evidence favoring use in pediatric CPB.

Allopurinol, NAC May reduce injury due to

free radicals. NAC

may improve myocardial

function.

No clear data.

NMDA antagonists

(magnesium, selfotel)

Reduce excitotoxicity No benefit in human trials.

Nimodipine (calcium channel antagonist)

Reduces cellular injury mediated

by calcium influx during reperfusion.

Negative results in human stroke trials.

Erythropoetin (EPO) EPO switches off apoptosis

Limits excitotoxic cell death

Mediated by NMDA - R

Blocks the inflammatory cascade

EPO is a cerebral vasodilator

EPO 1000 units/kg IV for 3 doses –

12 hours pre-op / after CPB then 24

hours after.

CPB: cardiopulmonary bypass; EEG: electroencephalograph; NAC: N-acetyl cysteine; NMDA: N-methyl D-aspartate

Langley SM, et al. Eur J Cardiothorac Surg 2000. Clancy RR, et al. Pediatrics 2001.Miller SP, et al. Ann thorac Surg 2004. Bickler PE, Fahlman CS. Anesth Analg 2006, 103.

Inhaled anesthetics

Isoflurane

Desflurane

Slowing of neuronal metabolism

Slow apoptosis and block iCa++

neuronal injury and death.

Be placed in the CPB sweep gas flow

Vasodilation

It would appear desirable to use this agents liberally on CPB.

Even seeking to achieve a target blood level while cooling. Especially if DHCA or other such techniques are to be used.

•EEG it is a rough guide to anesthetic depth it is affected by temperature,CPB,anesthetics not easy to use

•BIS (BISPECTRAL INDEX) it is currently used to guide the depth of anesthesia easy to use - less reliable during hypothermia

•SjVO2 (JUGULAR VENOUS BULB OXYMETRY) it is considered the gold standard of global cerebral oxygenation it is invasive Unilateral SjVO2 may not reflect contralateral events

•TCD (TRANSCRANIAL DOPPLER ULTRASOUND) it is a sensitive real-time monitor of CBF, can detect microemboli it monitor the middle cerebral artery Absent signal during DHCA.•S- 100B (Biochemical marker) Detects preexisting neurologic deficit Multiple sampling periods required•NIRS (NEAR-INFRARED SPECTROSCOPY) it is a non-invasive optical technique most devices utilize 2-4 wavelengths of infrared light at 700-1000 nm, where oxygenated and deoxygenated hemoglobin have distinct absorption spectra two depth of light penetration are used to subtract out data from the skin and skull resulting in brain oxygenation value Changes in cerebral vascular composition will affect rSO2 reading Useful during DHCA.

Conclusion

• Survival after neonatal and infant cardiac surgery has improved dramatically, but quality of life, including neurodevelopmental outcomes, still needs study and improvement. It is important to protect the brain using established strategies,and test new strategies with carefully designed follow-up studies. Potential exists for significant improvement in this area.