429CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation • BOX 38 1 a Adrenergic vs b Adrenergic Agonist Effects a Adrenergic Effects • Vasoconstrict peripheral vessels • Maintain aortic[.]
CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation required for a hemodynamically unstable rhythm is higher than that for a stable rhythm in children in whom the mean stimulus required for capture was between 52 and 65 mA After electrical capture is achieved, one must ascertain whether an effective arterial pulse is generated If pulses are not adequate, other resuscitative efforts should be used The most serious complication of TCP is induction of a ventricular arrhythmia.131 Fortunately, this complication is rare and may be prevented by pacing only in the demand mode Mild transient erythema beneath the electrodes is common Skeletal muscle contraction can be minimized by using large electrodes, a 40-ms pulse duration, and the smallest stimulus required for capture Sedatives or analgesics may be necessary in the patient who is awake If defibrillation or cardioversion is necessary, one must allow a distance of to cm between the electrode and paddles to prevent arcing of the current Pharmacology Adrenergic Agonists In 1963, only years after the original description of closed-chest CPR, Pearson and Redding described the use of adrenergic agonists for resuscitation.132 They subsequently showed that early administration of epinephrine in a canine model of cardiac arrest improved the success rate of CPR They also demonstrated that the increase in aortic diastolic pressure by administration of a-adrenergic agonists was responsible for the improved success of resuscitation They theorized that vasopressors such as epinephrine were of value because the drug increased peripheral vascular tone, not because of a direct effect on the heart.133 Yakaitis et al investigated the relative importance of a- and b-adrenergic agonist actions during resuscitation.134 Only 27% of dogs that received a pure b-adrenergic receptor agonist along with an a-adrenergic antagonist were resuscitated successfully compared with all of the dogs that received a pure a-adrenergic agonist and a b-adrenergic antagonist.134 Later studies reconfirmed this finding.135 Michael et al demonstrated that the a-adrenergic effects of epinephrine result in intense vasoconstriction of the resistance vessels of all organs of the body, except those supplying the heart and brain.43 Because of the widespread vasoconstriction in nonvital organs, adequate perfusion pressure—and, thus, blood flow to the heart and brain—can be achieved despite the fact that cardiac output is very low during CPR.60 The increase in aortic diastolic pressure associated with epinephrine administration during CPR is critical for maintaining coronary blood flow and enhancing the success of resuscitation Even though the contractile state of the myocardium is increased by use of b-adrenergic agonists in the spontaneously beating heart, b-adrenergic agonists actually may decrease myocardial blood flow during CPR by increasing intramyocardial wall pressure and vascular resistance This decrease in myocardial blood flow could redistribute intramyocardial blood flow away from the subendocardium, increasing the likelihood of ischemic injury to this region.136 Moreover, evidence indicates that left ventricular end-diastolic pressure (LVEDP) rises with epinephrine use, reducing the overall impact of the vasoconstrictor effects of epinephrine on CPP Tang et al showed elevated LVEDP and decreased measures of diastolic performance in epinephrine-resuscitated rats after induced VF compared with phenylephrine-resuscitated animals or epinephrine-resuscitated animals who also received a b-blocker.137 Similar data were found by McNamara, who used a rat pup model 429 • BOX 38.1 a-Adrenergic vs b-Adrenergic Agonist Effects a-Adrenergic Effects • • • • Vasoconstrict peripheral vessels Maintain aortic diastolic pressure Improve coronary blood flow No metabolic stimulatory effect b-Adrenergic Effects • • • • • • Vasodilate peripheral vessels Decrease aortic diastolic pressure Increase cellular metabolic rate Positive inotrope Increase intensity of ventricular fibrillation Increase heart rate and/or dysrhythmias following resuscitation of asphyxial arrest.138 LVEDP was increased and diastolic function indices were decreased with epinephrine compared with either saline solution alone or epinephrine combined with verapamil These data imply that excessive b-adrenergic effects prevent the intracellular calcium reuptake during diastole that is required for myocardial relaxation By its inotropic and chronotropic effects, b-adrenergic stimulation increases myocardial oxygen demand, which increases the risk of ischemic injury when superimposed on low coronary blood flow This combination of increased oxygen demand by b-adrenergic agonists and decreased oxygen supply may damage an already ischemic heart, raising the question of whether a pure a-adrenergic agonist would be better than epinephrine, with its significant b-adrenergic effects (Box 38.1).139 The effects on energy utilization and oxygen supply not only have implications for the success of the initial resuscitation but also for the postresuscitation function of the myocardium In an effort to address the balance of the risks and benefits of epinephrine, a large randomized controlled trial was conducted among five National Health Service ambulance companies in the United Kingdom.140 The PARAMEDIC2 trial enrolled 8014 adult patients with out-of-hospital cardiac arrest and randomized them to either standard-dose epinephrine or saline placebo Overall survival was improved in the epinephrine group (3.2% vs 2.4%), but there was no difference in rates of survival with favorable neurologic outcomes This finding is likely due to the much higher rates of severe neurologic impairment in the epinephrine survivors and is similar to results found in observational studies.141 A meta-analysis that included this study showed improved survival to admission with epinephrine but no improvement with survival to discharge or good neurologic outcome.142 Timing of epinephrine administration may have an impact Recent analyses of large resuscitation databases have shown that survival is greatest with early administration of epinephrine in both adult and pediatric patients.143–145 Another interesting finding from analyzing these large databases is that longer time periods between epinephrine doses than what is currently recommended may be associated with better survival to hospital discharge However, as this was a retrospective analysis, it warrants further investigation.146 A number of studies have attempted to compare a-adrenergic agonists to epinephrine during CPR Phenylephrine and methoxamine are two pure a-adrenergic agonists that have been used in animal models of CPR with success equal to that of epinephrine.60,134,136 More recently, vasopressin (discussed in depth later) has been studied as a noncatecholamine vasoconstrictor in the S E C T I O N I V Pediatric Critical Care: Cardiovascular management of patients who experience cardiac arrest.18 These agents cause peripheral vasoconstriction and increase aortic diastolic pressure, resulting in improved myocardial and cerebral blood flows This effect results in a higher oxygen supply/demand ratio in the ischemic heart and a theoretical advantage over the combined a- and b-adrenergic agonist effects of epinephrine These agonists, as well as vasopressors such as vasopressin, have been used successfully for resuscitation.18,133,147 These drugs maintain blood flow to the heart during CPR with similar performance to epinephrine In an animal model of VF cardiac arrest, a resuscitation rate of 75% was reported for both epinephrine- and phenylephrine-treated groups In this study, the ratio of endocardial to epicardial blood flow was lower in the group treated with epinephrine, suggesting the presence of subendocardial ischemia.60 However, studies of this kind are difficult to interpret because of the inability to measure the degree of a-receptor activation by the different vasopressors The higher subendocardial blood flow in the phenylephrine group may have been the result of less a-receptor activation.148–150 Moreover, some investigators have questioned the merits of using a pure a-adrenergic agonist during CPR Although the inotropic and chronotropic effects of b-adrenergic agonists may have deleterious hemodynamic effects during CPR administered for VF, increases in both heart rate and contractility increase cardiac output when spontaneous coordinated ventricular contractions are achieved Cerebral blood flow during CPR, like coronary blood flow, depends on peripheral vasoconstriction and is enhanced by use of a-adrenergic agonists This action produces selective vasoconstriction of noncerebral peripheral vessels to areas of the head and scalp without causing cerebral vasoconstriction.60 As with myocardial blood flow, pure a-agonist agents are as effective as epinephrine in generating and sustaining cerebral blood flow during CPR in adult animal models and in infant models.60,147 No difference in neurologic deficits was found at 24 hours after cardiac arrest between animals receiving either epinephrine or phenylephrine during CPR.151 Animal studies have shown transient improvements in cerebral oxygenation,152 and similarly in a prospective study of 36 adult patients, a bolus of epinephrine showed a small increase in cerebral oxygenation within the first minutes after administration.153 Analogous to the heart, b-adrenergic agonists could increase cerebral oxygen uptake if a sufficient amount of drug crosses the blood-brain barrier during or after resuscitation In addition, adrenergic agonists may vasoconstrict or dilate cerebral vessels depending on the balance between a- and b-adrenergic receptors Epinephrine and phenylephrine had similar effects on cerebral blood flow and metabolism, maintaining normal cerebral oxygen uptake for 20 minutes of CPR in dogs This finding implies that cerebral blood flow was high enough to maintain adequate cerebral metabolism and that b-receptor stimulation did not increase cerebral oxygen uptake, despite the fact that the combined effects of brain ischemia and CPR can increase the permeability of the blood-brain barrier to drugs used during CPR or when enzymatic barriers to vasopressors (e.g., by monoamine oxidase) are overwhelmed during tissue hypoxia Mechanical disruption of the barrier could occur during chest compressions by large fluctuations in cerebral venous and arterial pressures or as a result of hyperemia, the large increase in cerebral blood flow that occurs during the early reperfusion period when the cerebral vascular bed is maximally dilated following resuscitation, particularly if systemic hypertension occurs.154 No blood-brain barrier permeability changes during CPR immediately after resuscitation or hours &RQWURO &35 /RQJ&35 PLQSRVW KSRVW L P/JPLQ 430 3RQV 'LH 0&$ • Fig 38.9 Transfer coefficient (Ki) of a-aminoisobutyric acid for pons, di- encephalon (DIE), and middle cerebral (MCA) artery regions Control group: minutes ischemia and 10 minutes cardiopulmonary resuscitation (CPR); minutes ischemia and 40 minutes cardiopulmonary resuscitation; minutes after resuscitation; hours after resuscitation Group in each region, *P , 05, different from group by one-way analysis of variance and Dunnett test for all three regions (Modified from Schleien CL, Koehler RC, Schaffner DH, et al Blood-brain barrier disruption after cardiopulmonary resuscitation in immature swine Stroke 1991;22:477.) after resuscitation were found in adult dogs.154 However, after minutes of cardiac arrest and minutes of CPR in piglets, the blood-brain barrier was permeable to the small neutral amino acid a-aminoisobutyric acid hours after cardiac arrest (Fig 38.9).155,156 The increase in permeability could be prevented by prearrest administration of conjugated superoxide dismutase and catalase, indicating a role of oxygen free radicals in the pathogenesis of this injury to the blood-brain barrier (Fig 38.10).157 These endothelial membrane changes frequently were associated with the presence of intravascular polymorphonuclear and monocytic leukocytes.158 Whether leukocytes disrupt the blood-brain barrier by release of toxic substances, such as oxygen free radicals or proteases, or appear in the postischemic microvessels as an epiphenomenon of a more important derangement is unknown (Fig 38.11) Vasopressin The role of vasopressin as a noncatecholamine vasoconstrictor in the management of patients who experience cardiac arrest has received a great deal of interest Work by Lindner in Europe and Landry in the United States had established sufficient evidence of efficacy for its use to be included in the 2010 AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.112,159 Subsequent adult studies comparing standard-dose epinephrine with vasopressin alone or in combination with standard-dose epinephrine have showed that vasopressin offered no advantage in ROSC or survival to discharge.160 It has subsequently been removed from the 2015 AHA guidelines However, increasing evidence indicates that vasopressin is a useful agent in the management of shock of multiple etiologies Therefore, it may have a role in postresuscitation management CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation AIB transfer coefficien (µL/g per min) Thalamus Superior colliculus Midbrain Pons Spinal cord B Medulla Posteriormiddle border Anteriormiddle border Posterior cerebral artery Middle cerebral artery Anterior cerebral artery Caudate nucleus Group Group Group Cerebellum A Group Group Group Hippocampus AIB transfer coefficien (àL/g per min) 431 ãFig 38.10 (A) Transfer coefficient of a-aminoisobutyric acid (AIB) from plasma to brain in hippocampus, caudate nucleus, and primary supply and border regions of cerebral arteries in nonischemic time controls (group 1, n 5), ischemia group treated with polyethylene glycol (PEG; group 2, n 8), and ischemia group treated with PEG-superoxide dismutase and PEG-catalase (group 3, n 8) Error bars represent standard error of the mean (SEM) *P , 05 between groups and by Mann-Whitney U test (B) Transfer coefficient of AIB from plasma to brain in caudal brain regions in nonischemic time controls (group 1, n 5), ischemia group treated with PEG (group 2, n 8), and ischemia group treated with PEG-superoxide dismutase and PEG-catalase (group 3, i5 8) Error bars represent SEM *P , 05 between groups and by Mann-Whitney U test (Modified from Schleien CL, Eberle B, Schaffner DH, et al Reduced blood-brain barrier permeability after cardiac arrest by conjugated superoxide dismutase and catalase in piglets Stroke 1994;25[9]:1830–1834.) • Fig 38.11 Transmission electron micrograph of an infant piglet brain hours after minutes of cardiac arrest and minutes of cardiopulmonary resuscitation (magnification 35000) An intravascular leukocyte, which has the morphologic features of a monocyte, is adherent to the endothelial surface of a venule and appears to be occluding the lumen The luminal surface of the endothelial cell contains membrane blebs and discontinuities (From Caceres MJ, Schleien CL, Kuluz JW, et al Early endothelial damage and leukocyte accumulation in piglet brains following cardiac arrest Acta Neuropathol 1995;90[6]:582.) Arginine vasopressin is a short peptide hormone secreted by the posterior pituitary gland in response to changes in tonicity and in effective intravascular volume, signaled primarily via baroreceptor unloading in the aorta Severe shock is the most potent stimulus to vasopressin secretion Serum levels 20- to 200-fold higher than normal may be found immediately after cardiac arrest and in other severe shock states Despite these observations, lower than expected vasopressin levels have been found in some patients with profound shock, and patients dying of cardiac arrest have been found to have significantly lower vasopressin levels than survivors.161–165 The cause of lower than expected vasopressin levels in some patients is unclear Depletion of vasopressin stores may be a potential mechanism Dogs subjected to profound hemorrhagic shock have an early massive elevation of vasopressin levels immediately after the event, followed by a depression below expected levels within hour of the insult Severe depletion of vasopressin stores from the posterior hypophysis was noted.166 These animals developed a catecholamine-refractory vasodilatory shock that responded dramatically to low doses of vasopressin.167 These observations have led to an exploration of the use of vasopressin in both cardiac arrest and shock states Vasopressin is an extremely potent vasoconstrictor Its effects on vascular tone are primarily mediated through interaction with a specific G protein–coupled receptor referred to as the V1a-receptor, which is distributed widely throughout vascular beds.165 Of note, the V1a-receptor is linked to the same second messenger system as the a-adrenergic receptor that mediates vasoconstriction through alteration of intracellular calcium levels However, in the pulmonary circulation, vasopressin activation of V1-receptors mediates the release of nitric oxide and causes pulmonary vasodilatation Vasopressin also interacts with its V2-receptor, which regulates aquaporin expression on the renal collecting duct epithelium Stimulation of the V2-receptor occurs at substantially lower levels than those required to activate the V1a-receptor Vasopressin use during resuscitation has been studied in animals and humans In an adult porcine model of VF, vasopressin 432 S E C T I O N I V Pediatric Critical Care: Cardiovascular at a dose of 0.8 mg/kg was found to be superior to the maximally effective dose of epinephrine 200 mg/kg in restoring LV myocardial blood flow, increasing diastolic CPP and total cerebral blood flow as well as rates of ROSC.138 Moreover, the duration of the effect was sustained for minutes, compared with 1.5 minutes for epinephrine.18 Adverse effects noted in the postresuscitation phase included decreased renal and adrenal blood flows and reduced cardiac output.168,169 In a pediatric porcine model of cardiac arrest, vasopressin at a dose of 0.8 mg/kg was not as effective as epinephrine at 200 mg/kg in restoring LV myocardial blood flow or achieving ROSC.170 Only of animals achieved ROSC compared with of in the epinephrine group A combination group that received both epinephrine at 45 mg/kg and vasopressin at 0.8 mg/kg fared better with ROSC in of animals Possible explanations for the difference between adult and juvenile animals include different doseresponse curves for the two drugs, failure of maturation of vasopressin receptors, a different distribution of vasopressin receptors, or the different experimental model In an initial small, randomized clinical trial of vasopressin compared with epinephrine for refractory VF, the rate of achieving ROSC was higher in the vasopressin group.171 A large multicenter randomized trial of vasopressin for cardiac arrest in adults has been reported.172 More than 1200 patients were randomly assigned in the field to receive doses of either 40 international units (IU) of vasopressin or mg of epinephrine followed by additional treatment with epinephrine, if necessary In patients in whom ROSC was not achieved after two doses of medication, a third dose of medication such as epinephrine could be added at the resuscitating physician’s discretion Initial dose vasopressin was equivalent to epinephrine in achieving survival to both hospital admission and discharge in patients with either PEA or VF In patients with asystole, vasopressin was superior to epinephrine in achieving both survival to admission and discharge, although intact neurologic outcome was not improved In the group receiving a third dose of medication such as epinephrine, survival was greater in the vasopressin group In a study of 200 patients with in-hospital cardiac arrest, patients were randomly assigned to receive either mg of epinephrine or 40 IU of vasopressin Again, no statistical difference in survival to hour or to hospital discharge was found between groups or subgroups.173 The results of these studies led to the classification of evidence for vasopressin for use in adults as indeterminate in the 2010 AHA guidelines.112 Subsequently, a meta-analysis of 10 randomized trials, including a total of 6120 adult patients, showed that the use of vasopressin was neither beneficial nor harmful in an unselected patient population in terms of ROSC, survival to hospital admission or discharge, or favorable neurologic outcome However, chance of ROSC was significantly higher in inhospital cardiac arrest patients when vasopressin was used.174 The published experience with vasopressin in children who experience cardiac arrest is limited The first case series of vasopressin use in CPR reported the outcome of four children with six prolonged refractory cardiac arrests that were unresponsive to standard resuscitation efforts.175 Each child received one or more bolus doses of vasopressin (0.4 U/kg) as rescue therapy In all children, the initial rhythm was a form of PEA that deteriorated to asystole in four of six events Three children had ROSC for more than 60 minutes, including one child with asystole Two children survived for more than 24 hours and one survived to hospital discharge A review of a national registry of in-hospital CPR showed that patients who received vasopressin had a lower incidence of ROSC greater than 20 minutes (22 [34%] of 64) than patients who did not receive the medication (675 [55%] of 1229).176 The association of poor outcome with vasopressin persisted even with multivariate analysis with logistic regression to attempt to control for other factors that might affect ROSC The effect of vasopressin in pediatric arrest that was refractory to an initial epinephrine dose was evaluated in a pilot study Patients were given vasopressin after an initial dose of epinephrine and were compared with a retrospective matched cohort of patients who experienced cardiopulmonary arrest that required greater than two doses of a vasopressor, not including vasopressin Ten patients were enrolled; while there was an increased 24-hour survival, there was no difference in ROSC, survival to hospital discharge, or favorable neurologic status at discharge.177 The current evidence examines the use of vasopressin only as a potential alternative when standard therapies, such as epinephrine, fail to cause ROSC Unfortunately, variables such as dosing, timing of vasopressin infusion, or pediatric risk of mortality scores have not been controlled for in these studies No double-blinded, randomized controlled studies have been performed; thus, no firm recommendations are available concerning the use of vasopressin for CPR in infants and children The current recommended dose of vasopressin for adults in cardiac arrest is 40 IU No data comparing this dose to other doses are available, and concern exists regarding postresuscitation complications related to this dose We have selected 0.5 IU/kg as the standard for cardiac arrest Further data are needed before more definitive dosing recommendations can be made Use of vasopressin in postresuscitation management may be considered A relative vasopressin deficiency has been noted in a number of shock states, including hemorrhage, sepsis, and postCPB, as well as in patients who have unsuccessful resuscitations In these settings, shock may be refractory to catecholamines These patients may respond to a vasopressin infusion, allowing the weaning of high-dose catecholamines Although a role in the postresuscitation setting has not been demonstrated based on the data related to refractory shock, consideration of the use of vasopressin for refractory hypotension may be appropriate Additionally, the additive effects of combination drug therapy for adults with cardiac arrest may be most beneficial In a recent randomized, double-blind placebo control study investigating vasopressin plus epinephrine or saline placebo plus epinephrine with or without methylprednisolone, the group receiving combination therapy with vasopressin-epinephrine-methylprednisolone with CPR resulted in improved survival to hospital discharge with improved neurologic status.178,179 High-Dose Epinephrine The physiologic responses of animals and humans to higher doses of epinephrine include higher cerebral blood flow, increased myocardial and submyocardial blood flow, improved oxygen delivery relative to oxygen consumption, and less depletion of myocardial adenosine triphosphate (ATP) stores with more rapid repletion of phosphocreatine.149,180–184 Contrary results, with increased myocardial oxygen consumption and decreased myocardial blood flow, have been demonstrated during CPR following VF cardiac arrest.41,185 In a piglet model, high-dose epinephrine (HDE) produced lower myocardial blood flow than standard-dose epinephrine (SDE).180 In neonatal lambs following asphyxia-induced bradycardia, HDE resulted in a higher heart rate but lower stroke volume and cardiac output.186 Additionally, prolonged peripheral CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation vasoconstriction and excessive doses of epinephrine may delay or impair reperfusion of systemic organs, particularly the kidneys and gastrointestinal tract Studies regarding survival of patients who were given HDE have been contradictory In out-of-hospital patients who experienced cardiac arrest, HDE produced higher aortic diastolic pressure during CPR and increased the rate of ROSC compared with standard doses of epinephrine Gonzalez et al demonstrated a dose-dependent increase in aortic blood pressure by epinephrine in patients who failed to respond to prolonged resuscitative efforts.187 Paradis et al.187–189 showed that HDE increased aortic diastolic pressure and improved the rate of successful resuscitation in patients in whom ACLS protocols had failed This group also reported on a series of 20 children treated with HDE and compared them with 20 historic control subjects consisting of children with cardiac arrest treated with SDE.190 They reported that 14 of the children in the HDE group had ROSC, survived to hospital discharge, and were neurologically intact There were no survivors in the SDE comparison group Other centers have claimed that higher-than-standard doses of epinephrine during CPR in children improve the hemodynamics and increase the success of CPR However, no one has provided any valid data suggesting that HDE improves survival beyond the immediate postresuscitation period.91,189,191,192 Based on these studies, the 1992 AHA guidelines for pediatric advance life support recommended HDE if an initial SDE failed to resuscitate the child Three large multicenter studies were subsequently published that dampened enthusiasm for the use of HDE Stiell et al studied 650 cardiac arrest adult patients who were randomly assigned to receive either an SDE or HDE (7 mg) protocol.193 No differences were observed between the groups with regard to 1-hour survival (23% vs 18%), rate of hospital discharge (5% vs 3%), or neurologic outcome Brown et al reported on 1280 cardiac arrest adult patients who received either SDE (0.02 mg/kg) or HDE (0.2 mg/kg).24 Again, no differences in ROSC, short-term survival, survival to hospital discharge, or neurologic outcome were observed between the two groups of patients In a study of 816 adults, Callaham et al reported a higher ROSC in the HDE group.194 However, there were no differences in the rate of hospital discharge or ultimate survival of these patients In addition to these studies, a specific pediatric animal study was published that failed to demonstrate a clear survival benefit for HDE, although the occurrence of ROSC appeared to be greater.185 The 2000 AHA guidelines changed the recommendation for HDE to an option for second and subsequent doses of epinephrine A prospective, randomized, double-blind clinical trial of HDE in 68 pediatric inpatients was reported by Perondi et al.15 ROSC for more than 20 minutes was achieved in 15 of 34 patients who received HDE but in only of 34 patients who received SDE (P 07) However, survival to 24 hours occurred in only two of the HDE group versus seven of the SDE group (P 05) In the group that experienced an asphyxial arrest, none of 12 treated with HDE were alive at 24 hours, whereas of 18 patients in the SDE group survived Four survived to hospital discharge, and two patients were neurologically normal.15 A meta-analysis of epinephrine use in adult cardiac arrest showed no difference in survival to discharge or neurologic outcome when using high dose over standard dose.195 These studies reinforced concerns that HDE may account for some of the adverse effects that occur after resuscitation and is the basis of the 2015 AHA guidelines’ recommendation against the use of HDE during CPR.156,196,197 433 Atropine Atropine is a parasympatholytic agent that acts by blocking cholinergic stimulation of the muscarinic receptors of the heart, which usually results in an increase in the sinus rate and shortening of the atrioventricular node conduction time Atropine may also activate latent ectopic pacemakers It has little effect on systemic vascular resistance, myocardial perfusion pressure, or contractility.198 Atropine is indicated for treatment of asystole, PEA, bradycardia associated with hypotension, second- and third-degree heart block, and slow idioventricular rhythms In children who present in cardiac arrest, sinus bradycardia and asystole are the most common initial rhythms, which make atropine useful as a first-line drug Atropine is particularly effective in clinical conditions associated with excessive parasympathetic tone The recommended dose of atropine is 0.02 mg/kg, with a minimum dose of 0.1 mg and a maximum dose of 0.5 mg/dose Smaller doses than 0.1 mg, even in small infants, may result paradoxically in bradycardia because of a central stimulatory effect on the medullary vagal nuclei by a dose that is too low to provide anticholinergic effects on the heart, although this phenomenon has come under debate.198a,198b Atropine may be given by any route, including intravenous, endotracheal, interosseous, intramuscular, and subcutaneous Its onset of action occurs within 30 seconds, and its peak effect occurs between and minutes after an intravenous dose The recommended adult dose is 0.5 mg every minutes until the desired heart rate is obtained up to a maximum of mg For asystole, mg is given intravenously and repeated every minutes if asystole persists Full vagal blockade usually is obtained with a dose of mg in adults Because of its parasympatholytic effects, atropine should not be used in patients in whom tachycardia is undesirable In patients after myocardial infarction or ischemia with persistent bradycardia, atropine should be used in the lowest dose possible to increase heart rate Using the lowest possible dose will limit tachycardia, a potent contributor to increased myocardial oxygen consumption, which could lead to VF In addition, atropine should not be used in patients with pulmonary or systemic outflow tract obstruction or idiopathic hypertrophic subaortic stenosis because tachycardia decreases ventricular filling and lowers cardiac output in this setting Sodium Bicarbonate The administration of sodium bicarbonate results in an acid-base reaction in which bicarbonate combines with hydrogen to form carbonic acid, which dissociates into water and carbon dioxide Because of the generation of carbon dioxide, adequate alveolar ventilation must be present to achieve the normal buffering action of bicarbonate Use of sodium bicarbonate during CPR remains controversial because of its potential adverse effects and the lack of evidence showing any benefit from its use during CPR.199,200 Sodium bicarbonate is indicated for correction of significant metabolic acidosis, especially when signs of cardiovascular compromise are present Acidosis itself may have a number of negative effects on the circulation, including depression of myocardial function by prolonging diastolic depolarization, depressing spontaneous cardiac activity, decreasing the electrical threshold for VF, decreasing the inotropic state of the myocardium, and reducing the cardiac response to catecholamines Acidosis also decreases systemic vascular resistance and attenuates the vasoconstrictive ... In this study, the ratio of endocardial to epicardial blood flow was lower in the group treated with epinephrine, suggesting the presence of subendocardial ischemia.60 However, studies of this... cardiac arrest is 40 IU No data comparing this dose to other doses are available, and concern exists regarding postresuscitation complications related to this dose We have selected 0.5 IU/kg as... systemic outflow tract obstruction or idiopathic hypertrophic subaortic stenosis because tachycardia decreases ventricular filling and lowers cardiac output in this setting Sodium Bicarbonate The administration