drowning, near-drowning, and pediatric cardiac arrest

An Evaluation of Fluid An Evaluation of Fluid Resuscitation to Improve Outcome Resuscitation to Improve Outcome

in Infants and Children with Out-in Infants and Children with Out-of-Hospital Cardiopulmonary of-Hospital Cardiopulmonary

ArrestArrestPaul A. Checchia, MDPaul A. Checchia, MD

Division of Pediatric Critical Care MedicineDivision of Pediatric Critical Care Medicine

Loma Linda University Children’s HospitalLoma Linda University Children’s Hospital

Loma Linda, CaliforniaLoma Linda, California

HypothesisHypothesis

To determine whether the use of albumin during the resuscitation of pediatric patients who have suffered an out-of-hospital cardiopulmonary arrest reduces the severity of acute hypoxic-ischemic injury in comparison to 0.9 normal saline

Outcome MeasuresOutcome Measures

• Cardiovascular function

• Need and duration of inotropic support

• Need and duration of mechanical ventilation

• Length of stay in pediatric intensive care unit

• Length of stay in hospital

BackgroundBackground

• Pediatric Cardiopulmonary Arrest– Epidemiology and outcomes

• Resuscitation Practice– Current– Emerging therapies

• Albumin – Theoretical advantages and disadvantages

Introduction to Pediatric Introduction to Pediatric Cardiopulmonary ArrestCardiopulmonary Arrest

• Incidence and epidemiology

• Pathophysiologic changes

• Initial assessment and resuscitation

• Prognostic evaluation and outcomes

Pediatric Cardiopulmonary Pediatric Cardiopulmonary ArrestArrest

• Etiologies– In-hospital versus out-of-hospital

• Drowning: second only to motor vehicle accidents

– Other• Trauma (including abuse)• Underlying medical conditions

Incidence and EpidemiologyIncidence and EpidemiologyDrowningDrowning

• Second leading cause of injury related death in children less than 15 years old

• 6500 people drown each year in the United States

• 90% of all drowning deaths occur within 10 yards of safety

Geographic DistributionGeographic Distribution

• 10 Western states (including California) – Leading cause of death in children <14 years of age

• Highest incidence– Phoenix, Arizona

• Lowest incidence– Northeast United States

• Proximity to large bodies of water not necessarily a risk factor

Gender DifferencesGender Differences

• Males – 78% of all deaths from drowning

• Yearly incidence– 1/300 boys and 1/900 girls will be hospitalized

after a nonfatal immersion event– 1/1000 boys and 1/3000 girls will die from

drowning

Age DifferencesAge Differences

• Bimodal distribution– Peaks

• < 5 years• 15-19 years

• Alcohol involved in approximately 50% of adolescent drowning cases

Swimming Pool DrowningsSwimming Pool Drownings

• 50-90% of all pool drownings occur in children < 4 years old

• In 1993, 53% of all drownings occurred in swimming pools

• Quan et al. Pediatrics, 1989 – Adult supervision in 84% of cases– Only 18% witnessed the actual immersion

event

Sequence of Events During Sequence of Events During SubmersionSubmersion

• Contrary to popular opinion, the victim does not wave or call for help– Breathing instinctively takes precedence

• Upright posture, arms extended laterally, thrashing and slapping the water– Often mistaken for playing and splashing in

the water

Sequence of Events During Sequence of Events During SubmersionSubmersion

• Head submerges and surfaces several times during struggling activity

• Children can struggle for only 10 seconds

• Adults may be able to struggle for up to 60 seconds

Sequence of Events During Sequence of Events During SubmersionSubmersion

• PCO2 rises, diaphragm begins to have episodic contractions– Inspiration prevented only by voluntary

closure of the glottis– Eventually, involuntary gasp occurs

Sequence of Events During Sequence of Events During SubmersionSubmersion

• Laryngeal spasm – 20% of cases– No aspiration of water

Sequence of Events During Sequence of Events During SubmersionSubmersion

• Involuntary gasping continues for several minutes

• Swallowing of large volumes of water into stomach

• Consciousness lost within 3 minutes

• Water passively enters lungs

Sequence of Events During Sequence of Events During SubmersionSubmersion

• Cardiac arrythmias

• Convulsions and spasmodic efforts

• Death

Pathophysiologic ChangesPathophysiologic Changes Cardiovascular EffectsCardiovascular Effects

• Ischemia

• Ventricular fibrillation does occur but it is relatively uncommon

• Cardiogenic shock

Pathophysiologic ChangesPathophysiologic Changes Neurologic EffectsNeurologic Effects

• Timing of injury– Exact time of irreversible injury presently

unknown– ATP depletion in as little as 2 minutes of

hypoxia

Pathophysiologic ChangesPathophysiologic Changes Neurologic EffectsNeurologic Effects

• Cerebral edema 24 - 72 hours following injury

• Loss of autoregulation of blood flow

• Reperfusion injury

HypothermiaHypothermia

• Case reports of miraculous recovery

• Cerebral oxygen consumption 50% of normal at 28oC

HypothermiaHypothermia

• Cerebral blood flow decreases 6-7% per 1oC drop

• Negative effects include dysrhythmias, increased blood viscosity

• Must be cold before hypoxic

Secondary HypothermiaSecondary Hypothermia

• Majority of pediatric patients become hypothermic in response to cardiac arrest

• Body temperature spontaneously recovers in most

• Active rewarming measures “overshoot” in most cases

(Hickey et al. Pediatrics 2000)

Permissive HypothermiaPermissive Hypothermia

• Human data available and suggestive of positive neurologic affects– Holzer et al. Acta Anaesthesiol 1997– Colbourne et al. Mol Neurobiol 1997– Bernard et al. Ann Emerg Med 1997

Initial Assessment and Initial Assessment and ResuscitationResuscitation

Restating the obviousRestating the obvious

Initial Assessment and Initial Assessment and ResuscitationResuscitation

• Specialized issues– Heimlich maneuver: thought to clear airways

of liquid obstruction • Amount of fluid is usually small and non-

obstructive • May increase risk of aspiration of gastric contents• Do not waste time, correcting hypoxia is

paramount

Initial Assessment and Initial Assessment and ResuscitationResuscitation

• Threshold for intubation should be very low

• Indications for intubation– Arrest– Loss of airway protective reflexes – Deteriorating neurologic exam– Severe respiratory distress or hypoxia despite

supplemental oxygen– Hypothermia (core temperature < 30oC)

Initial Assessment and Initial Assessment and ResuscitationResuscitation

• Hypovolemia

• Marked vasoconstriction

• IV fluids

Resuscitation FluidsResuscitation Fluids

• Current practice– Normal Saline– 5% Albumin– 25% Albumin– Lactated Ringers Solution– Hypertonic Saline

• Choice dependent on provider, cost, habit

AlbuminAlbumin

• Historical perspective– Developed as blood substitute for combat

casualty victims during World War II – Studied in treatment of traumatic brain injury,

hypoxic injury following cardiac arrest in adults, and hepatic encephalopathy

• Small series• Adults only

AlbuminAlbumin

• Recent experimental data– Renewed interest in albumin as a potential

clinically relevant treatment specifically for ischemic and traumatic brain injury

Review of Experimental DataReview of Experimental Data

• Belayev et al. Brain Res 1999– Temporary forebrain ischemia in rats– Albumin infusion during injury and reperfusion

• Improvement in composite neurological scores at 7 days following injury

• Improvement in histological appearance of brain at 7 days following injury

• Belayev et al. Stroke 2001– Therapeutic window for albumin infusion determined

to be as long as 4 hours following injury

Albumin Infusion During InjuryAlbumin Infusion During InjuryProposed Mechanisms for ProtectionProposed Mechanisms for Protection

• Anti-inflammatory agent– Emerson TE, Crit Care Med 1989

• Reduction of platelet aggregation– Reduction of microvascular thrombosis

• Jorgensen et al. Thromb Res 1980

• Improved local blood flow – Reaction with nitric oxide

• Keaney et al J Clin Invest 1993

Albumin Infusion During InjuryAlbumin Infusion During InjuryProposed Mechanisms for ProtectionProposed Mechanisms for Protection

• Regulates pyruvate dehydrogenase– Improved cellular bioenergetics

• Tabernero et al. Glia 1999

• Binds free calcium– Directly decreases cellular injury

• Wortsman et al. Am J Physiol 1980

• Oxygen radical scavenger– Loban et al. Clin Sci 1997– Kooy et al. Crit Care Med 1995

OutcomesOutcomes Initial ResuscitationInitial Resuscitation

• Current approaches to resuscitation may increase the number of successful cardiovascular resuscitations without equal neurologic recovery

OutcomesOutcomes Long Term PrognosisLong Term Prognosis

• Overall, >15% survivors with significant neurologic deficits

• Children with spontaneous, purposeful movements and had a normal brainstem examination at 24 hours progressed to full recovery

• Those without these findings by 24 hours suffered severe neurologic deficits or death

(Bratton SL et al. Arch Pediatr Adolesc Med 1994)

Experimental DesignExperimental Design

• Patient Population– Pediatric (birth to 15 years of age) patients in cardiac

arrest.

• Inclusion Criteria– Patients who require cardiopulmonary resuscitation

(CPR) for cardiac or respiratory arrest will be considered eligible for the study. An arrest will be defined as the initiation of CPR by either bystanders or prehospital personnel

– Patients will be eligible for the study regardless of the etiology of arrest (i.e. drowning, arrhythmia, and respiratory arrest).

Experimental DesignExperimental Design

• Randomized controlled interventional trial.

• A power analysis will be preformed when 20 patients have been enrolled (10 in each arm) to determine how long the study would need to continue if any trends were noted.

• Patients will be randomized to one of two groups.

Experimental DesignExperimental Design

• Group 1/Even days – – ALS prehospital personnel will follow

approved ICEMA protocols.• Protocol Reference #7000 Pediatric Cardiac Arrest

(1Day to 8 years of Age) and • Protocol Reference #7002 Pediatric Cardiac Arrest

(9 to 15 years of Age)

Experimental DesignExperimental Design

• Group 2/Odd days – ALS prehospital personnel will follow the study

protocols.• Protocol Reference #7000TS Pediatric Cardiac Arrest (1Day

to 8 years of Age) and • Protocol Reference #7002TS Pediatric Cardiac Arrest (9 to

15 years of Age)

– Patients on odd days will receive a 20cc/kg initial bolus of 5% Albumin in place of Normal Saline. If the patient has a return of any perfusing rhythm they will receive and additional bolus of 20cc/kg of albumin. Otherwise, the protocols will remain identical.

Outcome MeasuresOutcome Measures

• Death• Cardiovascular function as measured by:

– Blood pressure, heart rate, and initial arterial blood gas measurements

– Echocardiogram– Need and duration of inotropic support

• Need and duration of mechanical ventilation• Modified Multi-organ Failure Score on Days 1, 2, 3, and

7– Serum Creatine– Cardiac Troponin I– Total Bilirubin

Outcome MeasuresOutcome Measures

• Lengths of stay in pediatric intensive care unit• Length of stay in hospital. • Admission neurologic examination as measured by the:

– Glasgow Coma Scale score– pupillary reactivity – other brain stem reflexes – presence of apnea

• Magnetic resonance imaging and spectroscopy abnormalities at post-arrest day 7.

• Pediatric Cerebral Performance Category Scale Score (PCPCS) at 6 to 12 months post injury.

• Glasgow Outcome Score (GOS) on discharge from PICUGOS on discharge from hospital

Data CollectionData Collection

• Run Sheets

• Emergency Department Records

• Admission Records

• History

Data CollectionData Collection

• All participating personnel will be contacted by investigator team member– Data collection only– Feedback on protocol design

• Improvements

– Update on current state of study

ResultsResults

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