439CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation use for young children was questioned because the arrhythmia detection algorithms driving these devices were developed for adults[.]
Trang 1CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation
use for young children was questioned because the
arrhythmia-detection algorithms driving these devices were developed for
adults Cecchin et al used the Heartstream FR2 Patient Analysis
System (Agilent) to analyze 696 5-second rhythms from 191
chil-dren younger than 12 years.290 Analysis revealed 100% accuracy
for nonshockable rhythms and 96% accuracy for VF This is
similar to the accuracy reported for adults In a more recent study,
Atkinson et al tested the accuracy of the Lifepak 500 AED
(Stryker) on 1561 15-second rhythms from 203 children aged
1 day to 7 years.270 The device correctly identified 99% of coarse
VF as shockable and 99.1% of nonshockable rhythms A number
of manufacturers (Zoll and Agilent) have developed energy-reduc-ing electrodes that should allow use of these devices in young children.270
Since the 2000 AHA guidelines, data have shown that AEDs can be safely and effectively used in children of all ages Current guidelines recommend use of an AED in children between the ages of 1 and 8 years who have no signs of circulation, though they have been used successfully in younger children and in-fants.291 The device should be adapted to deliver a pediatric dose
Identify and treat underlying cause
PEDIATRIC TACHYCARDIA
With a pulse and poor perfusion
• Maintain patent airway; assist breathing as needed
• Oxygen
• Cardiac monitor to identify rhythm; monitor blood pressure and oximetry
• IO/IV access
• 12-lead ECG if available; don’t delay therapy
Evaluate QRS duration
Evaluate rhythm
with 12-lead
ECG or monitor
Possible ventricular tachycardia
Probable sinus tachycardia
• Compatible history consistent
with known cause
• P waves present/normal
• Variable R-R; constant PR
• Infants: rate usually <220 min
• Children: rate usually <180 min
Probable supraventricular tachycardia
• Compatible history (vague, nonspecific) history of abrupt rate changes
• P waves absent/abnormal
• HR not variable
• Infants: rate usually ≥220 min
• Children: rate usually ≥180 min
Cardiopulmonary compromise?
• Hypotension
• Acutely altered mental status
• Signs of shock
• If IO/IV access present, give adenosine
OR
• If IO/IV access not available,
or if adenosine ineffective, synchronized cardioversion
Search for and
(no delays)
Doses/details Synchronized cardioversion:
Begin with 0.5-1 J/kg;
if not effective, increase to 2 J/kg.
Sedate if possible but don’t delay cardioversion.
Adenosine IO/IV dose:
First dose: 0.1 mg/kg rapid bolus (maximum:
6 mg).
Second dose:
0.2 mg/kg rapid bolus (maximum second dose 12 mg).
Amiodarone IO/IV dose:
5 mg/kg over 20-60 minutes
or Procainamide IO/IV dose:
15 mg/kg over 30-60 minutes
Do not routinely administer amiodarone and procainamide together.
Expert consultation advised
• Amiodarone
• Procainamide
Synchronized cardioversion adenosineConsider
if rhythm regular and QRS monomorphic
2
8
13
1
3
10
• Fig. 38.15 American Heart Association guidelines for management of ventricular arrhythmias.
ABCs, Airway, breathing, and circulation; BLS, basic life support; CPR, cardiopulmonary resuscitation;
ECG,electrocardiogram;HR,heartrate;IO,intraosseous;IV,intravenous;PEA,pulselesselectricalactiv-ity;TT,trachealtube;VF,ventricularfibrillation;VT,ventriculartachycardia.
Trang 2with the use of a pediatric attenuator system that decreases the
de-livered energy to a dose suitable for children When an attenuator
system is not available, then the standard adult pads with
corre-sponding dose should be delivered In children younger than 1 year
of age, a manual defibrillator is preferred; however, an AED with or
without a pediatric attenuator should be used if necessary.265
Antiarrhythmics
Amiodarone is an effective antiarrhythmic agent for both atrial
and ventricular arrhythmias The role of amiodarone in cardiac
arrest was established after a series of studies demonstrated
effi-cacy and superiority of amiodarone over lidocaine in the
manage-ment of refractory VF and pulseless ventricular tachycardia in
adults Compared with lidocaine, amiodarone led to substantially
higher rates of survival to hospital admission in patients with
shock-resistant out-of-hospital VF.292 These findings led to major
changes in the AHA guidelines for management of ventricular
arrhythmias (Table 38.1 and Figs 38.15 and 38.16)
The growing pediatric experience among experts and inference
from adult studies led to inclusion of amiodarone in the 2000
AHA Pediatric Advanced Life Support (PALS) guidelines and
continued in the 2015 AHA PALS guidelines as a drug of choice,
alongside lidocaine, for pulseless VT or VF.49 For
hemodynami-cally stable VT, it is also a drug of choice, with the level of
evi-dence classified as IIb Procainamide remains an alternative drug
choice Amiodarone is commonly used for management of
post-operative atrial and junctional ectopic tachycardia, especially in
patients with ventricular pacing wires in place
The wide range of effectiveness of amiodarone is demonstrated
by the array of indications noted in the 2015 AHA guidelines for
adults.196 Its role in the management of atrial arrhythmias in adults
includes the following: as an adjunct to electrical cardioversion of
refractory paroxysmal supraventricular tachycardia and atrial
tachycardia, for rate control, for pharmacologic conversion of atrial
flutter, and for control of rapid ventricular response in preexcited
atrial tachyarrhythmias It is the drug of choice for junctional
tachycardia with poor function If function is preserved,
amioda-rone is an acceptable alternative to a b-blocker or calcium channel
blocker Its role in ventricular arrhythmias is outlined in Box 38.2
The pharmacology of amiodarone is complex and may partially explain the wide range of efficacy It is poorly absorbed orally and must be loaded intravenously in urgent situations It is primarily classified as a Vaughan Williams class III agent that blocks the ATP-sensitive outward potassium channels, causing prolongation of the action potential and refractory period However, this effect requires intracellular accumulation Upon intravenous loading, the antiar-rhythmic effects primarily result from noncompetitive a- and
b-adrenergic receptor blockade, calcium channel blockade, and effects
on inward sodium current causing a decrease in anterograde conduc-tion across the atrioventricular node and an increase in the effective atrioventricular refractory period The full antiarrhythmic impact requires a loading period for up to 1 to 3 weeks to achieve intracel-lular levels and full potassium channel blocking effects Prolongation
of the QT interval, an effect resulting from potassium (K)-ATP channel blockade, is commonly described with amiodarone use However, it does not manifest until several days into loading, under-scoring its different effects during the acute period and after loading
is accomplished These effects are evident throughout all cardiac tis-sue, which may explain amiodarone’s efficacy for so many arrhyth-mias, both atrial and ventricular The a-adrenergic blockade leads to vasodilatation, which may increase coronary blood flow
Immediate hemodynamic effects of amiodarone are caused by the solubilizing agent Tween 80, which has both vasodilating and myocardial depressant effects.293 Hypotension is commonly re-ported with intravenous administration and may limit the rate at which the drug can be given The overall hemodynamic impact of intravenous administration depends on the balance of its effect on rate control, myocardial performance, and vasodilatation Cardiac output usually is unchanged or increases despite the decreased contractility because of both rate control and vasodilatation The effect on systemic vascular resistance and the limited impact on contractility make amiodarone the drug of choice for use in pa-tients with impaired cardiac function
The drug is highly lipid soluble, giving it a very large volume
of distribution, which accounts for the need for loading over many days Until all tissues are saturated, rapid redistribution out
of the vascular compartment may lead to early recurrence of ar-rhythmias Once tissue saturation has occurred, the half-life is estimated to be between 13 and 103 days
TABLE
38.1 Drug Therapy for Pulseless Arrest
100 mg/kg
1:10,000 (0.1 mL/kg) 1:1000 should be used for ETT (0.1 mL/kg) Atropine IV, IO, ET, SC 0.02 mg/kg (minimum dose 0.1 mg) or
0.04–0.06 mg/kg via ETT
0.3 3 weight (kg) 3 base deficit 1 mEq/mL0.5 mEq/mL
Magnesium IV (IO) 25–50 mg/kg for torsades de pointes or
ET, Endotracheal; ETT, endotracheal tube; IO, intraosseous; IV, intravenous; SC, subcutaneous.
Trang 3CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation
Dosage recommendations for children are based on limited clinical studies and extrapolation of adult data For life-threaten-ing arrhythmias, the usual recommended dose is 5 mg/kg admin-istered intravenously This dose can be repeated if necessary to control the arrhythmia Intravenous loading doses are followed
by a continuous infusion of 10 to 20 mg/kg per day if there is a risk for arrhythmia recurrence The ideal rate of bolus adminis-tration is unclear; however, once diluted, the drug is given by intravenous push in adults The potential for profound vasodila-tation in children has led to concern by some pediatric intensiv-ists and cardiologintensiv-ists, who recommend that amiodarone be given over 10 minutes, as recommended in the package insert This concern may not be valid in the pulseless-arrest setting An alter-native dosing regimen for children is administration of 1 mg/kg pushes every 5 minutes up to 5 mg/kg This dose can be repeated
up to 10 mg/kg if the arrhythmia is not controlled Use of the small-aliquot bolus technique may be particularly appropriate for infants younger than 6 to 12 months
• Fig. 38.16 American Heart Association guidelines for management of bradycardia. ABCs, Airway,
breathing, and circulation; ALS, advanced life support; AV, atrioventricular; BLS, basic life support;
CPR,cardiopulmonaryresuscitation;IO,intraosseous;IV,intravenous.
Identify and treat underlying cause
• Maintain patent airway; assist breathing as necessary
• Oxygen
• Cardiac monitor to identify rhythm; monitor blood pressure and oximetry
• IO/IV access
• 12-lead ECG if available; don’t delay therapy
Cardiopulmonary compromise continues?
CPR if HR <60/min
with poor perfusion despite oxygenation and ventilation
• Epinephrine
• Atropine for increased vagal
tone or primary AV block
• Consider transthoracic pacing/
transvenous pacing
• Treat underlying causes
• Support ABCs
• Give oxygen
• Observe
• Consider expert
consultation
Bradycardia persists?
If pulseless arrest develops, go to Cardiac Arrest Algorithm
Doses/details Epinephrine IO/IV dose:
0.01 mg/kg (0.1 mL/kg)
of 1:10,000 concentration).
Repeat every 3–5 minutes.
If IO/IV access not available but endotracheal (ET) tube
in place, may give ET dose:
0.1 mg/kg (0.1 mL/kg of 1:1000).
Atropine IO/IV dose:
0.02 mg/kg May repeat once.
Minimum dose 0.1 mg and maximum single dose 0.5 mg.
PEDIATRIC BRADYCARDIA
With a pulse and poor perfusion
• Hypotension
• Acutely altered mental status
• Signs of shock
Cardiopulmonary compromise
No
No
Yes
Yes
4a
5
6
3 2
4 1
• BOX 38.2 Amiodarone (Intravenous)
• Intravenous amiodarone affects sodium, calcium channels, and a- and
b-adrenergic blocking properties The drug is useful for treatment of both
atrial and ventricular arrhythmias.
• Amiodarone is also helpful for ventricular rate control of rapid atrial
arrhythmias in patients with severely impaired LV function when digitalis
has proved ineffective Amiodarone is recommended after defibrillation and
epinephrine in cardiac arrest with persistent VT or VF.
• Amiodarone is effective for control of hemodynamically stable VT, polymorphic
VT, and wide-complex tachycardia of uncertain origin.
• Amiodarone is an adjunct to electrical cardioversion of refractory PSVTs,
atrial tachycardia, and pharmacologic cardioversion of AF.
• Amiodarone can control rapid ventricular rate due to accessory pathway
conduction in preexcited atrial arrhythmias.
AF, Atrial fibrillation; LV, left ventricular; PSVT, paroxysmal supraventricular tachycardia;
VF, ventricular fibrillation; VT, ventricular tachycardia.
Trang 4Amiodarone administered intravenously leaches plasticizers,
particularly di(2-ethylhexyl)phthalate, from polyvinyl chloride
This effect is enhanced at low infusion rates and at higher drug
concentrations, which may be minimized by frequent
intermit-tent boluses Whether these plasticizers have any significant
toxic-ity at these doses is unknown, although evidence indicates
testicu-lar vacuolization in rodents Additional caution is warranted in
neonates because the solution contains benzyl alcohol, which is
associated with metabolic acidosis and death in premature infants
Identification of the potential for these adverse events has led the
manufacturer to issue a statement to health care professionals
as-serting that use of intravenously administered amiodarone in
pe-diatrics is not recommended The AHA has responded with a
re-iteration of the recommendation for intravenous amiodarone use
in the 2015 guidelines for emergency cardiac care In the
recom-mendation, it concludes that practitioners should obtain expert
consultation because complications may include bradycardia,
heart block, and torsades de pointes VT Adverse reactions to
amiodarone can be life-threatening The drug prolongs the QT
interval In a series by Etheridge et al., 29 of 50 infants and
chil-dren experienced mild-to-moderate prolongation of the QTc.294
In the series by Burri et al., “most” infants experienced
prolonga-tion.295 Although none of the pediatric case series described the
development of drug-induced arrhythmias in patients,
amioda-rone-induced torsades de pointes has been described in case
re-ports, and, although less common than in adults, caution is
war-ranted.296 Use of amiodarone should be avoided in combination
with other drugs that prolong the QT interval In addition,
cau-tion should be exercised in the setting of hypomagnesemia and
other electrolyte abnormalities that predispose to torsades de
pointes Severe bradycardia and heart block have been described,
especially in the postoperative period Ventricular pacing wires are
recommended in this setting
The manufacturer of the intravenous preparation (Pfizer)
re-ports in the product literature a series of 61 children receiving
amiodarone, of whom 36% had hypotension, 20% had
bradycar-dia, and 15% had atrioventricular block These complications
were severe or life-threatening in some cases In a retrospective
cohort study, Maghrabi et al showed that amiodarone caused
cardiovascular collapse in 10% of pediatric patients Age,
hypo-tension, and rapid bolus delivery were independent risk factors for
collapse, and mortality rate was higher in the collapse group.297
Lidocaine is a Vaughan Williams class Ib agent that inhibits
fast inward sodium current, primarily affecting the ventricular
myocardium, and produces a decrease in automaticity Cells in
the sinoatrial and atrioventricular node are minimally affected It
is highly selective for depressed myocardial tissue Proarrhythmic
effects are relatively uncommon, though high plasma
concentra-tions are associated with depressed myocardial function, especially
in patients with underlying poor myocardial function The
half-life is 5 to 10 minutes, though hypokalemia can decrease its effect
The loading dose is 1 mg/kg, with an infusion rate of 20 to 50 mg/
kg per minute Since this agent does not increase the QTc
inter-val, its use is preferable to amiodarone in patients with a
pro-longed QTc
Subsequent to the publication of the 2015 AHA guidelines,
Valdes et al examined the use of amiodarone and lidocaine in
in-hospital pediatric patients with pulseless VT or VF They
found that lidocaine was independently favorably associated with
ROSC and 24-hour survival but not survival to hospital
dis-charge However, amiodarone did not have any association with
survival outcomes.3 Amiodarone, lidocaine, and placebo were compared head-to-head in a recent large randomized controlled trial in adults with out-of-hospital cardiac arrest with shock-re-fractory VF or pulseless VT.298 While there were some differences
in survival to hospital admission, neither drug demonstrated improved survival to hospital discharge or better neurologic out-come compared with placebo A subsequent meta-analysis has shown a similar result.299
Procainamide is a Vaughan Williams class Ia agent that slows the upstroke of the action potential by blocking sodium channels This slows conduction in atrial and ventricular muscle cells and suppresses normal and abnormal automaticity Procainamide in-creases the PR interval, the QRS duration, and prolongs the QTc interval Amiodarone and ranitidine increase procainamide levels The intravenous bolus dose is 10 to 15 mg/kg, and a continuous infusion of 30 to 80 mg/kg per minute may be used High doses have a negative inotropic effect and caution should be exercised in patients with a prolonged QT interval, LV dysfunction, or sinus dysfunction The risk of proarrhythmia, especially torsades de pointes, is moderate and not related to serum drug concentrations
Postresuscitation Care
Hemodynamic instability is common after cardiac arrest A per-sistently low cardiac index may lead to multiorgan failure and
is associated with early death within the first 24 hours after arrest.300 , 301 Systolic hypotension in the 6-hour period after a pe-diatric cardiac arrest has also been found to be associated with in-hospital mortality and worse neurologic outcomes.302 , 303 Ther-apies to address low cardiac output states have included the use of inodilators Inodilators (dobutamine and milrinone) augment cardiac output with little effect on myocardial oxygen demand
An inodilator can be used to treat myocardial dysfunction with increased systemic or pulmonary vascular resistance.304 , 305 Admin-istration of fluids may be required because of the vasodilatory effects Milrinone has a long half-life, which delays reaching a steady-state hemodynamic effect after changing the infusion rate
In the case of toxicity, adverse effects may persist for several hours after the infusion is discontinued Lewis et al compared dobuta-mine to milrinone therapy in adult cardiogenic shock and showed that they have similar times to resolution of shock.306 However, arrhythmia was more common with dobutamine and hypoten-sion was more common with milrinone
Amelioration of neurologic injury after cardiac arrest has been
a goal of many investigators (Box 38.3) Two multicenter trials on mild hypothermia after cardiac arrest, one from Europe and the other from Australia, showed initial promise In both studies, adult patients presenting with out-of-hospital VF who were resus-citated underwent rapid cooling to a target temperature between 32.8°C and 34.8°C, maintained for 12 to 24 hours Both neuro-logic outcome and mortality were improved compared with the control groups The odds ratio for improved neurologic outcome was 1.4 in the European study, which included 275 patients, and 5.25 in the Australian study, which included 77 randomized pa-tients The hypothermia groups had lower mean blood pressure, required more frequent use of epinephrine, and had higher sys-temic vascular resistance
Criticisms of these trials have included that they have a limited generalizability and that the control groups were not temperature controlled to avoid hyperthermia, which is known to worsen neurologic outcomes.307 , 308 To that end, the Targeted Temperature
Trang 5CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation
Management trials sought to further investigate if mild
hypother-mia conferred any benefit over a controlled normotherhypother-mia.309 The
trial compared temperature maintenance at 33°C versus 36°C in
unconscious adult survivors of the entire out-of-hospital cardiac
arrest patient population, regardless of reason for arrest The trial
showed no difference in survival between the two groups nor in
the secondary outcome of survival and neurologic outcome
Sub-sequent studies evaluating targeted temperature management did
not find differences in the systemic inflammatory response or
cognitive outcome at 6 months between the 33°C and 36°C
groups.310–312 A meta-analysis and consensus statement by
Don-nino et al found that there was no difference in mortality or
outcome when comparing 32°C versus 36°C and recommended a
targeted temperature management in adults between 32°C and
36°C for at least 24 hours.313
The Therapeutic Hypothermia after Pediatric Cardiac Arrest
(THAPCA) Trials sought to evaluate mild hypothermia versus
controlled normothermia in unconscious children suffering
from either in-hospital or out-of-hospital cardiac arrest.11 , 12
Eligible patients between the age of 48 hours and 18 years were
randomized to mild hypothermia (target temperature of
33.0°C) or therapeutic normothermia (36.8°C) No difference
between survival or functional outcome was found at 1 year
Subsequent analyses of both the THAPCA cohorts showed that
hypothermia did not influence neurologic or neurobehavioral
outcomes at 1 year, but that survivors of out-of-hospital arrest
had more significant declines in function than survivors of
in-hospital arrest.314–316
Future Directions
Despite the aforementioned therapeutic advances, continued
ef-forts to clarify their applicability to infants and children are vital
Clinical trials have been hampered by the federal regulation known as the “final rule” for resuscitation research.317 In 1996, as part of a broad-ranging effort to protect patients’ rights as human subjects, the standard of community consent for research that required immediate intervention was developed Since that time, resuscitation research in both adults and children has been lim-ited, with most trials conducted in Europe, Australia, and other countries, often with US collaborators The feasibility of defining
a community standard to perform a hypothetical trial of hypo-thermia after post–cardiac arrest in children was tested in 2004.318 The relevant community was defined as hospital staff and the parents of ICU patients and parents of previously resuscitated children They concluded that development of a study using an exemption from informed consent was feasible However, in an accompanying editorial, Moler reiterates that, despite feasibility, practicality is very different, as evidenced by the complete lack of pediatric resuscitation trials since 1996.317 Whether revision of this rule will occur or techniques for acquiring community con-sent can be developed remains one of the major hurdles to future pediatric resuscitation research
• BOX 38.3 Experimental Cerebroprotective Therapy
• Calcium channel blockers
• Glutamate receptor antagonists
• Opiate receptor antagonists
• Central a 2 -receptor antagonists
• b-Receptor antagonists
• Oxygen radical scavengers
• Iron chelators
• Xanthine oxidase inhibitors
• Inhibitors of arachidonic acid metabolism
• Thrombolytic agents
• Lazeroids
• Cerebral vasodilators
• Metabolic activators/inhibitors
• Hypothermia
• Nitric oxide synthase inhibitors
• Adenosine agonists
• Antiplatelet agents
• Antineutrophil strategies
• Protease inhibitors
• Growth factors
Key References
Donnino MW, Andersen LW, Berg KM, et al Temperature management after cardiac arrest: an advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care,
Peri-operative and Resuscitation Circulation 2015;132(25):2448-2456.
Hoyme DB, Patel SS, Samson RA, et al Epinephrine dosing interval and
survival outcomes during pediatric in-hospital cardiac arrest Resusci-tation 2017;117:18-23.
Kudenchuk PJ, Brown SP, Daya M, et al Amiodarone, lidocaine, or
placebo in out-of-hospital cardiac arrest N Engl J Med 2016;374(18):
1711-1722.
Moler FW, Silverstein FS, Holubkov R, et al Therapeutic hypothermia
after out-of-hospital cardiac arrest in children N Engl J Med
2015;372(20):1898-1908.
Morris MC, Wernovsky G, Nadkarni VM Survival outcomes after extra-corporeal cardiopulmonary resuscitation instituted during active chest compressions following refractory in-hospital pediatric cardiac
arrest Pediatr Crit Care Med 2004;5(5):440-446.
Perkins GD, Ji C, Deakin CD, et al A randomized trial of epinephrine
in out-of-hospital cardiac arrest N Engl J Med 2018;379(8):711-721.
Perondi MBM, Reis AG, Paiva EF, Nadkarni VM, Berg RA A compari-son of high-dose and standard-dose epinephrine in children with
cardiac arrest N Engl J Med 2004;350(17):1722-1730.
Sutton RM, French B, Meaney PA, et al Physiologic monitoring of CPR quality during adult cardiac arrest: a propensity-matched cohort
study Resuscitation 2016;106:76-82.
Sutton RM, Friess SH, Naim MY, et al Patient-centric blood pressure-targeted cardiopulmonary resuscitation improves survival from
car-diac arrest Am J Respir Crit Care Med 2014;190(11):1255-1262.
Topjian AA, French B, Sutton RM, et al Early postresuscitation hypo-tension is associated with increased mortality following pediatric
cardiac arrest Crit Care Med 2014;42(6):1518-1523.
The full reference list for this chapter is available at ExpertConsult.com