Circulation Atmegiso tmO Learn and live JOURNAL OF THE AMERICAN HEART ASSOCIATION Part 7.4: Monitoring and medications Circulation 2005; 112, 78-83; originally published online Nov 28, 2005 DOI: 10.1161/CIRCULATIONAHA. 105.166559 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, Tx 72514 Copyright o 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online ISSN:15244539 The online version of this article, along with updated information and services, is located on the World wide web at http://circ.ahajournals.org/cgi/content/full/112/24suppl/iv-78 Subscriptions: Information about subscribing to Circulation is online at http://circ.ahajournals.org/subsriptions/ Permissions: Permissions Rights Desk, Lippincott Williams Wilkins, 351 West Cam Street. Baltimore MD 21202-2436 Phone 410-5280-4050. Fax: 410-528-8550 En journalpermissions@lww.com Reprints: Information about reprints can be found online at http://www.Iww.com/static/html/reprints.html Downloaded from circ. ahajournals. org by on February 21, 2006
ISSN: 1524-4539 Copyright © 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX DOI: 10.1161/CIRCULATIONAHA.105.166559 Circulation 2005;112;78-83; originally published online Nov 28, 2005; Part 7.4: Monitoring and Medications http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-78 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/static/html/reprints.html Reprints: Information about reprints can be found online at journalpermissions@lww.com Street, Baltimore, MD 21202-2436. Phone 410-5280-4050. Fax: 410-528-8550. Email: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, 351 West Camden http://circ.ahajournals.org/subsriptions/ Subscriptions: Information about subscribing to Circulation is online at Downloaded from circ.ahajournals.org by on February 21, 2006
Part 7.4: Monitoring and medications is section provides an overview of monitoring techniques carbia (and therefore the adequacy of ventilation during and medications that may be useful during CPR and in the CPR), or tissue acidosis. This conclusion is supported by I mediate prearrest and postarrest settings. case series(LOE 5)and 10 case reports 0-l9 that showed that arterial blood gas values are an inaccurate indicator of the Monitoring Immediately Before, During, and magnitude of tissue acidosis during cardiac arrest and CPR After arrest both in and out of hospital Assessment During CPR Oximetry At present there are no reliable clinical criteria that clinicians During cardiac arrest, pulse oximetry will not function can use to assess the efficacy of CPR. Although end-tidal CO2 se pulsatile blood serves as an indicator of cardiac output produced by chest beds. But pulse oximetry is commonly used i compressions and may indicate return of spontaneous circu- lation(ROSC), 1. 2 there is little other technology available to department departments and critical care units for monitoring patients provide real-time feedback on the effectiveness of CPR who are not in arrest because it provides a simple, continuous method of tracking oxyhemoglobin saturation. Normal pulse Assessment of Hemodynamics oximetry saturation, however, does not ensure adequate systemic oxygen delivery because it does not calculate the Coronary Perfusion Pressure Coronary perfusion pressure(CPP= aortic relaxation [diastolic] otal oxygen content(O2 bound to hemoglobin dissolved pressure minus night atrial relaxation phase blood pressure) O2)and adequacy of blood flow(cardiac output) during CPr correlates with both myocardial blood flow and CPR, but it may provide a mechanism to assess tissue ROSC Increased CPP correlates with improved 24-hour sur- rapidly with cardiac conjunctival oxygen tension falls perfusion because tra vival rates in animal studies (loe 6 and is associated with arrest and returns to baseline when improved myocardial blood flow and ROSC in animal studies of pontaneous circulation is restored. 20,21 epinephrine, vasopressin, and angiotensin II (OE 6).5-7 End-Tidal CO, Monitoring When intra-arterial monitoring is in place during the End-tidal CO, monitoring is a safe and effective noninvasive resuscitative effort(eg, in an intensive care setting), tl indicator of cardiac output during CPR and may be an early clinician should try to maximize arterial diastolic pressures to indicator of ROSC in intubated achieve an optimal CPP. Assuming a right atrial diastolic CO, continues to be generated throughout the body.The pressure of 10 mm Hg means that the aortic diastolic pressure major determinant of CO2 excretion is its rate of delivery should ideally be at least 30 mm Hg to maintain a CPP of from the peripheral production sites to the lungs. In the 20 mm Hg during CPR. Unfortunately such monitoring is low-flow state during CPR, ventilation is relatively high ely available outside the int compared with blood flow, so that the end-tidal CO, concen Pulses tration is low. If ventilation is reasonably constant, then Clinicians frequently try to palpate arterial pulses during changes in end-tidal COz concentration reflect changes in chest compressions to assess the effectiveness of compres- cardiac output sions. No studies have shown the validity or clinical utility of Eight case series have shown that patients who were checking pulses during ongoing CPR. Because there are no successfully resuscitated from cardiac arrest had significantly valves in the inferior vena cava, retrograde blood flow into higher end-tidal CO2 levels than patients who could not be the venous system may produce femoral vein pulsations. resuscitated(LOE 5).2.22-28 Capnometry can also be used as Thus palpation of a pulse in the femoral triangle may indicate an early indicator of ROSC (LOE 529.3, LOE 63) venous rather than arterial blood flow. Carotid pulsations In case series totaling 744 intubated adults in cardiac arrest flow or myocardial or cerebral perfusion during CPP blood receiving CPR who had a maximum end-tidal CO,of during CPR do not indicate the efficacy of coronary <10 mm Hg, the prognosis was poor even if CPR was ptimized (Loe 5).2,24125,3233 But this prognostic indicator Assessment of Respiratory Gases was unreliable immediately after starting CPR in 4 studies Arterial Blood Gases (LOE 5).232.33 that showed no difference in rates of rosC Arterial blood gas monitoring during cardiac arrest is not a and survival in those with an initial end-tidal co, of reliable indicator of the severity of tissue hypoxemia, hyper <10 mm Hg compared with higher end-tidal CO2. Five patients achieved ROSC (one survived to discharge) despite (Circulation. 2005: 112: lV-78-IV-83) o 2005 American Heart Association an initial end-tidal CO, of <10 mm hg In summary, end-tidal CO2 monitoring during cardiac This special supplement to Circulation is freely available at http://www.circulationaha.org rrest can be useful as a noninvasive indicator of cardiac output generated during CPR(Class Ila). Further research is DOI: 10.1161/CIRCULATIONAHA 105. 166559 needed to define the capability of end-tidal CO V78
Part 7.4: Monitoring and Medications This section provides an overview of monitoring techniques and medications that may be useful during CPR and in the immediate prearrest and postarrest settings. Monitoring Immediately Before, During, and After Arrest Assessment During CPR At present there are no reliable clinical criteria that clinicians can use to assess the efficacy of CPR. Although end-tidal CO2 serves as an indicator of cardiac output produced by chest compressions and may indicate return of spontaneous circulation (ROSC),1,2 there is little other technology available to provide real-time feedback on the effectiveness of CPR. Assessment of Hemodynamics Coronary Perfusion Pressure Coronary perfusion pressure (CPP aortic relaxation [diastolic] pressure minus right atrial relaxation phase blood pressure) during CPR correlates with both myocardial blood flow and ROSC (LOE 3).3,4 A CPP of 15 mm Hg is predictive of ROSC. Increased CPP correlates with improved 24-hour survival rates in animal studies (LOE 6)5 and is associated with improved myocardial blood flow and ROSC in animal studies of epinephrine, vasopressin, and angiotensin II (LOE 6).5–7 When intra-arterial monitoring is in place during the resuscitative effort (eg, in an intensive care setting), the clinician should try to maximize arterial diastolic pressures to achieve an optimal CPP. Assuming a right atrial diastolic pressure of 10 mm Hg means that the aortic diastolic pressure should ideally be at least 30 mm Hg to maintain a CPP of 20 mm Hg during CPR. Unfortunately such monitoring is rarely available outside the intensive care environment. Pulses Clinicians frequently try to palpate arterial pulses during chest compressions to assess the effectiveness of compressions. No studies have shown the validity or clinical utility of checking pulses during ongoing CPR. Because there are no valves in the inferior vena cava, retrograde blood flow into the venous system may produce femoral vein pulsations.8 Thus palpation of a pulse in the femoral triangle may indicate venous rather than arterial blood flow. Carotid pulsations during CPR do not indicate the efficacy of coronary blood flow or myocardial or cerebral perfusion during CPR. Assessment of Respiratory Gases Arterial Blood Gases Arterial blood gas monitoring during cardiac arrest is not a reliable indicator of the severity of tissue hypoxemia, hypercarbia (and therefore the adequacy of ventilation during CPR), or tissue acidosis. This conclusion is supported by 1 case series (LOE 5)9 and 10 case reports10–19 that showed that arterial blood gas values are an inaccurate indicator of the magnitude of tissue acidosis during cardiac arrest and CPR both in and out of hospital. Oximetry During cardiac arrest, pulse oximetry will not function because pulsatile blood flow is inadequate in peripheral tissue beds. But pulse oximetry is commonly used in emergency departments and critical care units for monitoring patients who are not in arrest because it provides a simple, continuous method of tracking oxyhemoglobin saturation. Normal pulse oximetry saturation, however, does not ensure adequate systemic oxygen delivery because it does not calculate the total oxygen content (O2 bound to hemoglobin dissolved O2) and adequacy of blood flow (cardiac output). Tissue oxygen tension is not commonly evaluated during CPR, but it may provide a mechanism to assess tissue perfusion because transconjunctival oxygen tension falls rapidly with cardiac arrest and returns to baseline when spontaneous circulation is restored.20,21 End-Tidal CO2 Monitoring End-tidal CO2 monitoring is a safe and effective noninvasive indicator of cardiac output during CPR and may be an early indicator of ROSC in intubated patients. During cardiac arrest CO2 continues to be generated throughout the body. The major determinant of CO2 excretion is its rate of delivery from the peripheral production sites to the lungs. In the low-flow state during CPR, ventilation is relatively high compared with blood flow, so that the end-tidal CO2 concentration is low. If ventilation is reasonably constant, then changes in end-tidal CO2 concentration reflect changes in cardiac output. Eight case series have shown that patients who were successfully resuscitated from cardiac arrest had significantly higher end-tidal CO2 levels than patients who could not be resuscitated (LOE 5).2,22–28 Capnometry can also be used as an early indicator of ROSC (LOE 529,30; LOE 631). In case series totaling 744 intubated adults in cardiac arrest receiving CPR who had a maximum end-tidal CO2 of 10 mm Hg, the prognosis was poor even if CPR was optimized (LOE 5).1,2,24,25,32,33 But this prognostic indicator was unreliable immediately after starting CPR in 4 studies (LOE 5)1,2,32,33 that showed no difference in rates of ROSC and survival in those with an initial end-tidal CO2 of 10 mm Hg compared with higher end-tidal CO2. Five patients achieved ROSC (one survived to discharge) despite an initial end-tidal CO2 of 10 mm Hg. In summary, end-tidal CO2 monitoring during cardiac arrest can be useful as a noninvasive indicator of cardiac output generated during CPR (Class IIa). Further research is needed to define the capability of end-tidal CO2 monitoring to (Circulation. 2005;112:IV-78-IV-83.) © 2005 American Heart Association. This special supplement to Circulation is freely available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.105.166559 IV-78
Part 7. 4: Monitoring and Medications /V-79 aggressive interventions or a decision to abandon of 2 to 10 ug/min. Note that this is the nonarrest infusion resusc re efforts preparation and dose(ie, for bradycardia or hypotension) n the patient with RoSC, continuous or intermittent monitoring of end-tidal CO, provides assurance that the The use of vasopressin in cardiac arrest is discussed in Part endotracheal tube is maintained in the trachea. End-tidal CO2 can guide ventilation, especially when correlated with the 7. 2. Like epinephrine, vasopressin may be used in prearr Paco2 from an arterial blood gas measurement and postarrest conditions. Vasopressin has been used for lent of vasodilatory shock, such as septic she Medications for Cardiovascular Support sepsis syndrome. 39,40 Standard therapy for vasodilat Vasoactive drugs may be administered immediately before, shock includes antimicrobial agents, intravascular expansion, vasopressors, and inotropic agents that during, and after an arrest to support cardiac output, espe- lly blood flow to the heart and brain. Drugs may be myocardial contractility. Inotropic agents and vasoconstrictor selected to improve heart rate(chronotropic effects), myocar drugs that are commonly used in this setting, however, may have a diminished vasopressor action. If conventional dial contractility (inotropic effects), or arterial pressure(va- adrenergic vasopressor drugs are ineffective, a continuous soconstrictive effects), or to reduce afterload(vasodilator infusion of vasopressin may be beneficial(Class IIb). 4. effects). Unfortunately many adrenergic drugs are not sele tive and may increase or decrease heart rate and afterload Norepinephrine increase cardiac arrhythmias, and increase myocardial ische- Norepinephrine (levarterenol) is a naturally occurring potent mia by creating a mismatch between myocardial oxygen vasoconstrictor and inotropic agent. Cardiac output may demand and delivery. Myocardial ischemia, in turn, may on vascular resistance, the functional state of the left ventri- have metabolic effects that increase blood glucose, lactate cle and reflex responses(eg, those mediated by and metabolic rate aortic baroreceptors) Norepinephrine usually induces renal Specific drug infusion rates cannot be recommended be- and mesenteric vasoconstriction; in sepsis, however, norepi- ause of variations in pharmacokinetics(relation between nephrine improves renal blood flow and urine output.43. It drug dose and concentration) and pharmacodynamics (rela- may be effective for management of patients with severe tion between drug concentration and effect)in critically ill hypotension(eg, systolic blood pressure <70 mm Hg)and a patients,34,35 so initial dose ranges are listed below. Vasoac- low total peripheral resistance who fail to respond to less tive drugs must be titrated at the bedside to secure the potent adrenergic drugs such as dopamine, phenylephrine, or intended effect while limiting side effects. Providers must also be aware of the concentrations delivered and compati- Norepinephrine is relatively contraindicated in patients bilities with previously and concurrently administered drugs with hypovolemia. It may increase myocardial oxygen re- In general, adrenergic drugs should not be mixed with quirements, mandating cautious use in patients with ischemic sodium bicarbonate or other alkaline solutions in the intrave- heart disease. As noted above, extravasation may cause ischemic and sloughing of superficial tissues and agents are inactivated in alkaline solutions. 36.37 Norepineph- must be treated promptly rine (levarterenol) and other catecholamines that activate pinephrine is administer a-adrenergic receptors may produce tissue necrosis if extrav nephrine or 8 mg of norepinephrine bitartrate (I mg of norepi- sation occurs If extravasation develops, infiltrate 5 to 10 nephrine is equivalent to 2 mg of norepinephrine bitartrate)to of phentolamine diluted in 10 to 15 mL of saline into the site 250 mL of Dsw or 5% dextrose in normal saline(but not of extravasation as soon as possible to prevent tissue death normal saline alone), resulting in a concentration of 16 ug/mL of and sloughing. norepinephrine or 32 ug/mL of norepinephrine bitartrate. The nitial dose of norepinephrine is 0.5 to l ug/min titrated to effect. Epinephrine It should not be administered in the same iv line as alkaline The use of epinephrine in cardiac arrest is discussed in Part solutions, which may inactivate it 7.2:Management of Cardiac Arrest. "Epinephrine can also Dopamine be used in patients who are not in cardiac arrest but who Dopamine hydrochloride is a catecholamine-like agent and require inotropic or vasopressor support. For example, epi- chemical precursor of norepinephrine that stimulates both a nephrine is considered Class IIb for symptomatic bradycardia and B-adrenergic receptors. In addition, there are receptors if atropine and transcutaneous pacing fail or pacing is not specific for this compound(DAI, DA2 dopaminergic recep available(eg, in the out-of-hospital setting). It may also be tors ). Physiologically dopamine stimulates the heart through used in cases of anaphylaxis associated with hemodynamic both a-and B-receptors Pharmacologically dopamine is both instability or respiratory distress. 38 a potent adrenergic receptor agonist and a strong peripher To create a continuous infusion of epinephrine hydrochlo- dopamine receptor agonist. These effects are dose depender ride for treatment of bradycardia or hypotension, add I mg( During resuscitation dopamine is often used to treat hypo- mL of a 1: 1000 solution) to 500 mL of normal saline or Ds w. tension, especially if it is associated with symptomatic The initial dose for adults is I ug/min titrated to the desired bradycardia or after ROSC. Dopamine in combination with emodynamic response, which is typically achieved in doses other agents, including dobutamine, remains an option for
guide more aggressive interventions or a decision to abandon resuscitative efforts. In the patient with ROSC, continuous or intermittent monitoring of end-tidal CO2 provides assurance that the endotracheal tube is maintained in the trachea. End-tidal CO2 can guide ventilation, especially when correlated with the PaCO2 from an arterial blood gas measurement. Medications for Cardiovascular Support Vasoactive drugs may be administered immediately before, during, and after an arrest to support cardiac output, especially blood flow to the heart and brain. Drugs may be selected to improve heart rate (chronotropic effects), myocardial contractility (inotropic effects), or arterial pressure (vasoconstrictive effects), or to reduce afterload (vasodilator effects). Unfortunately many adrenergic drugs are not selective and may increase or decrease heart rate and afterload, increase cardiac arrhythmias, and increase myocardial ischemia by creating a mismatch between myocardial oxygen demand and delivery. Myocardial ischemia, in turn, may decrease heart function. Moreover, some agents may also have metabolic effects that increase blood glucose, lactate, and metabolic rate. Specific drug infusion rates cannot be recommended because of variations in pharmacokinetics (relation between drug dose and concentration) and pharmacodynamics (relation between drug concentration and effect) in critically ill patients,34,35 so initial dose ranges are listed below. Vasoactive drugs must be titrated at the bedside to secure the intended effect while limiting side effects. Providers must also be aware of the concentrations delivered and compatibilities with previously and concurrently administered drugs. In general, adrenergic drugs should not be mixed with sodium bicarbonate or other alkaline solutions in the intravenous (IV) line because there is evidence that adrenergic agents are inactivated in alkaline solutions.36,37 Norepinephrine (levarterenol) and other catecholamines that activate -adrenergic receptors may produce tissue necrosis if extravasation occurs. If extravasation develops, infiltrate 5 to 10 mg of phentolamine diluted in 10 to 15 mL of saline into the site of extravasation as soon as possible to prevent tissue death and sloughing. Epinephrine The use of epinephrine in cardiac arrest is discussed in Part 7.2: “Management of Cardiac Arrest.” Epinephrine can also be used in patients who are not in cardiac arrest but who require inotropic or vasopressor support. For example, epinephrine is considered Class IIb for symptomatic bradycardia if atropine and transcutaneous pacing fail or pacing is not available (eg, in the out-of-hospital setting). It may also be used in cases of anaphylaxis associated with hemodynamic instability or respiratory distress.38 To create a continuous infusion of epinephrine hydrochloride for treatment of bradycardia or hypotension, add 1 mg (1 mL of a 1:1000 solution) to 500 mL of normal saline or D5W. The initial dose for adults is 1 g/min titrated to the desired hemodynamic response, which is typically achieved in doses of 2 to 10 g/min. Note that this is the nonarrest infusion preparation and dose (ie, for bradycardia or hypotension). Vasopressin The use of vasopressin in cardiac arrest is discussed in Part 7.2. Like epinephrine, vasopressin may be used in prearrest and postarrest conditions. Vasopressin has been used for management of vasodilatory shock, such as septic shock and sepsis syndrome.39,40 Standard therapy for vasodilatory septic shock includes antimicrobial agents, intravascular volume expansion, vasopressors, and inotropic agents that increase myocardial contractility. Inotropic agents and vasoconstrictor drugs that are commonly used in this setting, however, may have a diminished vasopressor action.41 If conventional adrenergic vasopressor drugs are ineffective, a continuous infusion of vasopressin may be beneficial (Class IIb).42 Norepinephrine Norepinephrine (levarterenol) is a naturally occurring potent vasoconstrictor and inotropic agent. Cardiac output may increase or decrease in response to norepinephrine, depending on vascular resistance, the functional state of the left ventricle, and reflex responses (eg, those mediated by carotid and aortic baroreceptors). Norepinephrine usually induces renal and mesenteric vasoconstriction; in sepsis, however, norepinephrine improves renal blood flow and urine output.43,44 It may be effective for management of patients with severe hypotension (eg, systolic blood pressure 70 mm Hg) and a low total peripheral resistance who fail to respond to less potent adrenergic drugs such as dopamine, phenylephrine, or methoxamine. Norepinephrine is relatively contraindicated in patients with hypovolemia. It may increase myocardial oxygen requirements, mandating cautious use in patients with ischemic heart disease. As noted above, extravasation may cause ischemic necrosis and sloughing of superficial tissues and must be treated promptly. Norepinephrine is administered by adding 4 mg of norepinephrine or 8 mg of norepinephrine bitartrate (1 mg of norepinephrine is equivalent to 2 mg of norepinephrine bitartrate) to 250 mL of D5W or 5% dextrose in normal saline (but not in normal saline alone), resulting in a concentration of 16 g/mL of norepinephrine or 32 g/mL of norepinephrine bitartrate. The initial dose of norepinephrine is 0.5 to 1 g/min titrated to effect. It should not be administered in the same IV line as alkaline solutions, which may inactivate it. Dopamine Dopamine hydrochloride is a catecholamine-like agent and a chemical precursor of norepinephrine that stimulates both - and -adrenergic receptors. In addition, there are receptors specific for this compound (DA1, DA2 dopaminergic receptors). Physiologically dopamine stimulates the heart through both - and -receptors. Pharmacologically dopamine is both a potent adrenergic receptor agonist and a strong peripheral dopamine receptor agonist. These effects are dose dependent. During resuscitation dopamine is often used to treat hypotension, especially if it is associated with symptomatic bradycardia or after ROSC. Dopamine in combination with other agents, including dobutamine, remains an option for Part 7.4: Monitoring and Medications IV-79
I-80 Circulation December 13. 2005 management of postresuscitation hypotension. If hypotension Milrinone is more often used today because it has a shorter persists after filling pressure (ie, intravascular volume) half-life than inamrinone and is less likely to cause thrombo- optimized, drugs with combined inotropic and vasopressor cytopenia. 8.49 Milrinone is renally excreted with a half-life of actions like epinephrine or norepinephrine may be used. around 1 to 2 hours, so it requires 47 to 6 hours to achieve Positive effects include increases in both cardiac output and near-steady state concentrations if given without a loading arterial perfusion pressure. Although low-dose dopamine dose. A slow milrinone IV loading dose (50 ug/kg over 10 infusion has been frequently recommended to maintain renal minutes) is followed by an IV infusion at a rate of 0.375 to failed to show a beneficial effect from such therapy 45.4 A blood flow or improve renal function, more recent data 0.75 ug/kg per minute(375 to 750 ng/kg per minute) for 2 to 3 days. In renal failure the dose should be reduced. Adverse The usual dose of dopamine ranges from 2 to 20 ug/kg per effects include nausea, vomiting, and hypotension. minute. Doses >10 to 20 ug/kg per minute may be associated with systemic and splanchnic vasoconstriction. Higher doses Calcium of dopamine, like all adrenergic vasoconstrictor drugs, can be Although calcium ions play a critical role in myocardial contractile performance and impulse formation, retrospective associated with adverse effects on splanchnic perfusion in and prospective studies in the cardiac arrest setting have ome patients shown no benefit from calcium administration 50,51 Further Dobutamine more, high serum calcium levels induced by calcium admin- Dobutamine hydrochloride is a synthetic catecholamine and tration may be detrimental. For this reason, calcium should potent inotropic agent useful for treatment of severe systolic not be used routinely to support circulation in the setting of heart failure. Dobutamine has complex pharmacology be- cardiac arrest. When hyperkalemia, ionized hypocalcemia cause of the effects of the different racemic components. The (eg, after multiple blood transfusions), or calcium channel (+ isomer is a potent B-adrenergic agonist, whereas the blocker toxicity is present, use of calcium is probably Isomer potent ar-agonist 47 The vasodilating B helpful. 52 Ideally, ionized calcium concentration should be adrenergic effects of the (+)isomer counterbalance the measured because total calcium concentration does not cor- vasoconstricting a-adrenergic effects, often leading to little relate well with ionized concentration in critically change or a reduction in systemic vascular resistance. The patients.5354 beneficial effects of dobutamine may be associated with When necessary, a 10% solution(100 mg/mL) of calcium decreased left ventricular filling pressure. In addition to its chloride can be given in a dose of 8 to 16 mg/kg of the salt direct inotropic effects, dobutamine may further increas (usually 5 to 10 mL) and repeated as necessary. (The 10% stroke volume through reflex peripheral vasodilation(barone solution contains 1.36 mEq of calcium or 27. 2 mg elemental ceptor mediated), reducing ventricular afterload, so that calcium per milliliter.) arterial pressure is unchanged or may fall even though cardiac Digitalis output increases. Hemodynamic end points rather than a Digitalis preparations have limited use as inotropic agents in specific dose should be used to optimize treatment with emergency cardiovascular care. Digitalis decreases the ven- dobutamine tricular rate in some patients with atrial flutter or fibrillation The usual dose of dobutamine ranges from 2 to 20 ug/kg by slowing atrioventricular nodal conduction. The toxic to per minute; however, there is a wide variation in individual therapeutic ratio is narrow, especially when potassium deple response to the drug in critically ill patients. Elderly patients tion is present. Digitalis toxicity may cause serious ventric- may have a significantly decreased response to dobutamine. ular arrhythmias and At doses >20 ug/kg per minute, increases in heart rate of pecific antibody is available for the treatment of serious >10% may induce or exacerbate myocardial ischemia. Doses toxicity(Digibind, Digitalis Antidote BM) of dobutamine as high as 40 ug/kg per minute have been used, but such doses may greatly increase adverse effects, Nitroglycerin Nitrates are used for their ability to relax vascular smooth muscle. Nitroglycerin is the initial treatment of choice fo Inodilators(Inamrinone and Milrinone) suspected ischemic-type pain or discomfort (see Part 8 Inamrinone(formerly amrinone)and milrinone are phospho- Stabilization of the Patient With Acute Coronary diesterase Ill inhibitors that have inotropic and vasodilatory Syndrom properties. Phosphodiesterase inhibitors are often used IV nitroglycerin is also an effective adjunct in the treat- conjunction with catecholamines for severe heart failure, ment of congestive heart failure from any cause, 5 and it may cardiogenic shock, and other forms of shock unresponsive to be useful in hypertensive emergencies, particularly if related catecholamine therapy alone. Optimal use requires hemody- to volume overload. The action of nitroglycerin is mediated namic monitoring. These drugs are contraindicated in patients through local endothelial production of nitric oxide, particu- with heart valve stenosis that limits cardiac output. larly in the venous capacitance system. Nitroglycerin is most Inamrinone is administered as a loading dose of 0.75 effective in ts with increased vascular volume mg/kg over 10 to 15 minutes(may give over 2 to 3 minutes hypovolemia blunts the beneficial hemodynamic effects of if no left ventricular dysfunction)followed by an infusion of nitroglycerin and increases the risk of hypotension; nitrate- 5 to 15 ug/kg per minute, titrated to clinical effect. An induced hypotension typically responds well to fluid replace- additional bolus may be given in 30 minutes. ment therapy. Other potential complications of use of Iv
management of postresuscitation hypotension. If hypotension persists after filling pressure (ie, intravascular volume) is optimized, drugs with combined inotropic and vasopressor actions like epinephrine or norepinephrine may be used. Positive effects include increases in both cardiac output and arterial perfusion pressure. Although low-dose dopamine infusion has been frequently recommended to maintain renal blood flow or improve renal function, more recent data has failed to show a beneficial effect from such therapy.45,46 The usual dose of dopamine ranges from 2 to 20 g/kg per minute. Doses 10 to 20 g/kg per minute may be associated with systemic and splanchnic vasoconstriction. Higher doses of dopamine, like all adrenergic vasoconstrictor drugs, can be associated with adverse effects on splanchnic perfusion in some patients. Dobutamine Dobutamine hydrochloride is a synthetic catecholamine and potent inotropic agent useful for treatment of severe systolic heart failure. Dobutamine has complex pharmacology because of the effects of the different racemic components. The () isomer is a potent -adrenergic agonist, whereas the () isomer is a potent 1-agonist.47 The vasodilating 2- adrenergic effects of the () isomer counterbalance the vasoconstricting -adrenergic effects, often leading to little change or a reduction in systemic vascular resistance. The beneficial effects of dobutamine may be associated with decreased left ventricular filling pressure. In addition to its direct inotropic effects, dobutamine may further increase stroke volume through reflex peripheral vasodilation (baroreceptor mediated), reducing ventricular afterload, so that arterial pressure is unchanged or may fall even though cardiac output increases. Hemodynamic end points rather than a specific dose should be used to optimize treatment with dobutamine. The usual dose of dobutamine ranges from 2 to 20 g/kg per minute; however, there is a wide variation in individual response to the drug in critically ill patients. Elderly patients may have a significantly decreased response to dobutamine. At doses 20 g/kg per minute, increases in heart rate of 10% may induce or exacerbate myocardial ischemia. Doses of dobutamine as high as 40 g/kg per minute have been used, but such doses may greatly increase adverse effects, especially tachycardia and hypotension. Inodilators (Inamrinone and Milrinone) Inamrinone (formerly amrinone) and milrinone are phosphodiesterase III inhibitors that have inotropic and vasodilatory properties. Phosphodiesterase inhibitors are often used in conjunction with catecholamines for severe heart failure, cardiogenic shock, and other forms of shock unresponsive to catecholamine therapy alone. Optimal use requires hemodynamic monitoring. These drugs are contraindicated in patients with heart valve stenosis that limits cardiac output. Inamrinone is administered as a loading dose of 0.75 mg/kg over 10 to 15 minutes (may give over 2 to 3 minutes if no left ventricular dysfunction) followed by an infusion of 5 to 15 g/kg per minute, titrated to clinical effect. An additional bolus may be given in 30 minutes. Milrinone is more often used today because it has a shorter half-life than inamrinone and is less likely to cause thrombocytopenia.48,49 Milrinone is renally excreted with a half-life of around 11⁄2 to 2 hours, so it requires 41⁄2 to 6 hours to achieve near–steady state concentrations if given without a loading dose. A slow milrinone IV loading dose (50 g/kg over 10 minutes) is followed by an IV infusion at a rate of 0.375 to 0.75 g/kg per minute (375 to 750 ng/kg per minute) for 2 to 3 days. In renal failure the dose should be reduced. Adverse effects include nausea, vomiting, and hypotension. Calcium Although calcium ions play a critical role in myocardial contractile performance and impulse formation, retrospective and prospective studies in the cardiac arrest setting have shown no benefit from calcium administration.50,51 Furthermore, high serum calcium levels induced by calcium administration may be detrimental. For this reason, calcium should not be used routinely to support circulation in the setting of cardiac arrest. When hyperkalemia, ionized hypocalcemia (eg, after multiple blood transfusions), or calcium channel blocker toxicity is present, use of calcium is probably helpful.52 Ideally, ionized calcium concentration should be measured because total calcium concentration does not correlate well with ionized concentration in critically ill patients.53,54 When necessary, a 10% solution (100 mg/mL) of calcium chloride can be given in a dose of 8 to 16 mg/kg of the salt (usually 5 to 10 mL) and repeated as necessary. (The 10% solution contains 1.36 mEq of calcium or 27.2 mg elemental calcium per milliliter.) Digitalis Digitalis preparations have limited use as inotropic agents in emergency cardiovascular care. Digitalis decreases the ventricular rate in some patients with atrial flutter or fibrillation by slowing atrioventricular nodal conduction. The toxic to therapeutic ratio is narrow, especially when potassium depletion is present. Digitalis toxicity may cause serious ventricular arrhythmias and precipitate cardiac arrest. Digoxinspecific antibody is available for the treatment of serious toxicity (Digibind, Digitalis Antidote BM). Nitroglycerin Nitrates are used for their ability to relax vascular smooth muscle. Nitroglycerin is the initial treatment of choice for suspected ischemic-type pain or discomfort (see Part 8: “Stabilization of the Patient With Acute Coronary Syndromes”). IV nitroglycerin is also an effective adjunct in the treatment of congestive heart failure from any cause,55 and it may be useful in hypertensive emergencies, particularly if related to volume overload. The action of nitroglycerin is mediated through local endothelial production of nitric oxide, particularly in the venous capacitance system. Nitroglycerin is most effective in patients with increased intravascular volume. Hypovolemia blunts the beneficial hemodynamic effects of nitroglycerin and increases the risk of hypotension; nitrateinduced hypotension typically responds well to fluid replacement therapy. Other potential complications of use of IV IV-80 Circulation December 13, 2005
Part 7. 4: Monitoring and medications /v-81 nitroglycerin are tachycardia, paradoxical bradycardia, hy- wrapped in opaque material because nitroprusside deterio- poxemia caused by increased pulmonary ventilation- rates when exposed to light. The recommended dosing range perfusion mismatch, and headache. Nitroglycerin should be for sodium nitroprusside is 0. 1 to 5 ug/kg per minute, but avoided with bradycardia and extreme tachycardia or within higher doses(up to 10 ug/kg per minute)may be needed 24 to 48 hours of the use of phosphodiesterase inhibitors to treat erectile dysfunction IV Fluid administration Nitroglycerin is administered by continuous infusion(ni- Limited evidence is available to guide therapy. Volume troglycerin 50 or 100 mg in 250 mL of D, w or 0.9% sodiur loading during cardiac arrest causes an increase in right atrial chloride)at 10 to 20 ug/min and increased by 5 to 10 ug/ pressure relative to aortic pressure, 6o which can have the every 5 to 10 minutes until the desired hemodynamic or detrimental effect of decreasing CPP. The increase in CPP clinical response occurs. Low doses (30 to 40 ug/min) produced by epinephrine during CPR is not augmented by predominantly produce venodilatation; high doses (150 either an IV or intra-aortic fluid bolus in experimental CPR in ug/min) provide arteriolar dilatation. Uninterrupted adminis tration of nitroglycerin(>24 hours) produces tolerance. 6 If cardiac arrest is associated with extreme volume losses hypovolemic arrest should be suspected. These Sodium Nitroprusside present with signs of circulatory shock advancing to pulseless Sodium nitroprusside is a potent, rapid-acting, direct periph- electrical activity(PEA). In these settings intravascular vol- eral vasodilator useful in the treatment of severe heart failure ume should be promptly restored. In the absence of human and hypertensive emergencies. Its direct venodilator ef- studies the treatment of PEA arrest with volume repletion is fects decrease right and left ventricular filling pressure by based on evidence from animal studies 60-63 Current evidence increasing venous compliance. The net effect on venou return(preload) depends on the intravascular volume. in patients presenting with ventricular fibrillation(VF)nei- ther supports nor refutes the use of routine IV fluids(Class many patients cardiac output improves secondary to the Indeterminate) afterload-reducing effects of nitroprusside, meaning that ve Animal studies suggest that hypertonic saline may improve nous return must also increase, but the latter occurs at a lower survival from VF when compared with normal saline.64.6 end-diastolic pressure, resulting in relief of pulmonary con- Human studies are needed. however. before the use of gestion and reduced left ventricular volume and hypertonic saline can be recommended. If fluids are admin Arteriolar relaxation causes decreases in peripheral arterial istered during an arrest, solutions containing dextrose should esistance(afterload), resulting in enhanced systolic emptying be avoided unless there is evidence of hypoglycemia with reduced left ventricular volume and wall stress and reduced myocardial oxygen ce onsumption. In the presence of Sodium bicarbonate hypovolemia, nitroprusside can cause hypotension with reflex Tissue acidosis and resulting acidemia during cardiac arrest tachycardia. Invasive hemodynamic monitoring is useful and resuscitation are dynamic processes resulting from no blood flow during arrest and low blood flow during CPR. Although nitroprusside may be useful for the treatment of These processes are affected by the duration of cardiac arrest, pulmonary artery hypertension, it reverses hypoxic pulmo- the level of blood flow, and the arterial oxygen content durin nary vasoconstriction in patients with pulmonary disease(eg CPR. Restoration of oxygen content with appropriate venti- pneumonia,adult respiratory distress syndrome). The latter lation with oxygen, support of some tissue perfusion and effect may exacerbate intrapulmonary shunting, resulting some cardiac output with good chest compressions, then rapid worse hypoxemia. The major complication of nitroprusside is ROSC are the mainstays of restoring acid-base balance hypotension. Patients may also complain of headaches, nau- during cardiac arrest sea, vomiting, and abdominal Little data supports therapy with buffers during cardiac Nitroprusside is rapidly metabolized by nonenzymatic arrest. There is no evidence that bicarbonate improves like- means to cyanide, which is then detoxified in the liver and lihood of defibrillation or survival rates in animals with VF kidney to thiocyanate. Cyanide is also metabolized by form- cardiac arrest. a wide variety of adverse effects have been ing a complex with vitamin B1.58 Thiocyanate undergoes linked to bicarbonate administration during cardiac arrest. renal elimination. Patients with hepatic or renal insufficiency Bicarbonate compromises CPP by reducing systemic vascular and patients requiring >3 ug/kg per minute for more than 72 resistance. b It can create extracellular alkalosis that will shift hours may accumulate cyanide or thiocyanate, and they the oxyhemoglobin saturation curve and inhibits oxygen should be monitored for signs of cyanide or thiocyanate release. It can produce hypernatremia and therefore hyperos intoxication, such as metabolic acidosis. 59 When thiocyanate molarity. It produces excess carbon dioxide, which freely concentrations exceed 12 mg/dL, toxicity is manifested as diffuses into myocardial and cerebral cells and may paradox confusion, hyperreflexia, and ultimately convulsions. Treat- ically contribute to intracellular acidosis. 67 It can exacerbate ment of elevated cyanide or thiocyanate levels includes central venous acidosis and may inactivate simultaneously immediate discontinuation of the infusion. If the patient is administered catecholamines experiencing signs and symptoms of cyanide toxicity, sodium In some special resuscitation situations, such as preexisting nitrite and sodium thiosulfate should be administered metabolic acidosis, hyperkalemia, or tricyclic antidepressan Sodium nitroprusside is prepared by adding 50 or 100 mg overdose, bicarbonate can be beneficial(see Part 10: "Special to 250 mL of Ds W. The solution and tubing should be Resuscitation Situations")
nitroglycerin are tachycardia, paradoxical bradycardia, hypoxemia caused by increased pulmonary ventilationperfusion mismatch, and headache. Nitroglycerin should be avoided with bradycardia and extreme tachycardia or within 24 to 48 hours of the use of phosphodiesterase inhibitors to treat erectile dysfunction. Nitroglycerin is administered by continuous infusion (nitroglycerin 50 or 100 mg in 250 mL of D5W or 0.9% sodium chloride) at 10 to 20 g/min and increased by 5 to 10 g/min every 5 to 10 minutes until the desired hemodynamic or clinical response occurs. Low doses (30 to 40 g/min) predominantly produce venodilatation; high doses (150 g/min) provide arteriolar dilatation. Uninterrupted administration of nitroglycerin (24 hours) produces tolerance.56 Sodium Nitroprusside Sodium nitroprusside is a potent, rapid-acting, direct peripheral vasodilator useful in the treatment of severe heart failure and hypertensive emergencies.57 Its direct venodilatory effects decrease right and left ventricular filling pressure by increasing venous compliance. The net effect on venous return (preload) depends on the intravascular volume. In many patients cardiac output improves secondary to the afterload-reducing effects of nitroprusside, meaning that venous return must also increase, but the latter occurs at a lower end-diastolic pressure, resulting in relief of pulmonary congestion and reduced left ventricular volume and pressure. Arteriolar relaxation causes decreases in peripheral arterial resistance (afterload), resulting in enhanced systolic emptying with reduced left ventricular volume and wall stress and reduced myocardial oxygen consumption. In the presence of hypovolemia, nitroprusside can cause hypotension with reflex tachycardia. Invasive hemodynamic monitoring is useful during nitroprusside therapy. Although nitroprusside may be useful for the treatment of pulmonary artery hypertension, it reverses hypoxic pulmonary vasoconstriction in patients with pulmonary disease (eg, pneumonia, adult respiratory distress syndrome). The latter effect may exacerbate intrapulmonary shunting, resulting in worse hypoxemia. The major complication of nitroprusside is hypotension. Patients may also complain of headaches, nausea, vomiting, and abdominal cramps. Nitroprusside is rapidly metabolized by nonenzymatic means to cyanide, which is then detoxified in the liver and kidney to thiocyanate. Cyanide is also metabolized by forming a complex with vitamin B12. 58 Thiocyanate undergoes renal elimination. Patients with hepatic or renal insufficiency and patients requiring 3 g/kg per minute for more than 72 hours may accumulate cyanide or thiocyanate, and they should be monitored for signs of cyanide or thiocyanate intoxication, such as metabolic acidosis.59 When thiocyanate concentrations exceed 12 mg/dL, toxicity is manifested as confusion, hyperreflexia, and ultimately convulsions. Treatment of elevated cyanide or thiocyanate levels includes immediate discontinuation of the infusion. If the patient is experiencing signs and symptoms of cyanide toxicity, sodium nitrite and sodium thiosulfate should be administered. Sodium nitroprusside is prepared by adding 50 or 100 mg to 250 mL of D5W. The solution and tubing should be wrapped in opaque material because nitroprusside deteriorates when exposed to light. The recommended dosing range for sodium nitroprusside is 0.1 to 5 g/kg per minute, but higher doses (up to 10 g/kg per minute) may be needed. IV Fluid Administration Limited evidence is available to guide therapy. Volume loading during cardiac arrest causes an increase in right atrial pressure relative to aortic pressure,60 which can have the detrimental effect of decreasing CPP. The increase in CPP produced by epinephrine during CPR is not augmented by either an IV or intra-aortic fluid bolus in experimental CPR in dogs.61 If cardiac arrest is associated with extreme volume losses, hypovolemic arrest should be suspected. These patients present with signs of circulatory shock advancing to pulseless electrical activity (PEA). In these settings intravascular volume should be promptly restored. In the absence of human studies the treatment of PEA arrest with volume repletion is based on evidence from animal studies.60–63 Current evidence in patients presenting with ventricular fibrillation (VF) neither supports nor refutes the use of routine IV fluids (Class Indeterminate). Animal studies suggest that hypertonic saline may improve survival from VF when compared with normal saline.64,65 Human studies are needed, however, before the use of hypertonic saline can be recommended. If fluids are administered during an arrest, solutions containing dextrose should be avoided unless there is evidence of hypoglycemia. Sodium Bicarbonate Tissue acidosis and resulting acidemia during cardiac arrest and resuscitation are dynamic processes resulting from no blood flow during arrest and low blood flow during CPR. These processes are affected by the duration of cardiac arrest, the level of blood flow, and the arterial oxygen content during CPR. Restoration of oxygen content with appropriate ventilation with oxygen, support of some tissue perfusion and some cardiac output with good chest compressions, then rapid ROSC are the mainstays of restoring acid-base balance during cardiac arrest. Little data supports therapy with buffers during cardiac arrest. There is no evidence that bicarbonate improves likelihood of defibrillation or survival rates in animals with VF cardiac arrest. A wide variety of adverse effects have been linked to bicarbonate administration during cardiac arrest. Bicarbonate compromises CPP by reducing systemic vascular resistance.66 It can create extracellular alkalosis that will shift the oxyhemoglobin saturation curve and inhibits oxygen release. It can produce hypernatremia and therefore hyperosmolarity. It produces excess carbon dioxide, which freely diffuses into myocardial and cerebral cells and may paradoxically contribute to intracellular acidosis.67 It can exacerbate central venous acidosis and may inactivate simultaneously administered catecholamines. In some special resuscitation situations, such as preexisting metabolic acidosis, hyperkalemia, or tricyclic antidepressant overdose, bicarbonate can be beneficial (see Part 10: “Special Resuscitation Situations”). Part 7.4: Monitoring and Medications IV-81
lV-82 Circulation December 13, 2005 Sodium bicarbonate is not considered a first-line agent for 3. Paradis NA, Martin GB, Rivers EP, Goetting MG, Appleton TJ, the patient in cardiac arrest. When bicarbonate is used for M, Nowak RM. Coronary perfusion pressure and the return pecial situations, an initial dose of I mEq/kg is typical taneous circulation in human cardiopulmonary resuscitation Whenever possible, bicarbonate therapy should be guided by 4. Halperin HR, Tsitlik JE, Gelfand M, Weisfeldt ML, Gruben KG. Levin the bicarbonate concentration or calculated base deficit ob- HR, Rayburn BK, Chandra NC, Scott C, Kreps BJ, et al. A preliminary ained from blood gas analysis or laboratory measurement. To tudy of cardiopulmonary resuscitation by circumferential compression the chest with use of a pneumatic vest. N Engl J Med. 1993: 329: 762-768 minimize the risk of iatrogenically induced alkalosis, provid- 5. Kern KB, Ewy GA, Voorhees WD, Babbs CF, Tacker WA Myocardial ers should not attempt complete correction of the calculated ctor of 24-hour survival during prolonged base deficit. Other non-COz-generating buffers such as Car- dogs. Resuscitation. 1988: 16: 241-250 6 bicarb, Tham, or Tribonat have shown potential for minimi H. Prengel AW, Pfenninger EG. Lindner IM. Strohmenger HU M, Lurie KG. Vasopressin improves vital organ blood flow ing some adverse effects of sodium bicarbonate, including during closed-chest cardiopulmonary resuscitation in pigs. Circulation CO, generation, hyperosmolarity, hypernatremia, hypoglyce- 199591:215-221 mia, intracellular acidosis, myocardial acidosis, and"over- 7. Little CM, Angelos MG, Paradis NA. Compared to angiotensin Il, epi- nephrine is associated with high myocardial blood flow following retur shoot"alkalosis.68-70 But clinical experience is greatly lim- of spontaneous circulation after cardiac arrest. Resuscitation. 2003: 59: ted and outcome studies are lacking 353-359 8. Connick M, Berg RA. Femoral venous pulsations during open-chest Diuretics cardiac massage. Ann Emerg Med. 1994 24: 1176-1179. Furosemide is a potent diuretic agent that inhibits reabsorp- 9. Weil MH Rackow EC. Trevino R, Grundler W. Falk JL, Griffel MI. tion of sodium in the proximal and distal renal tubule and the Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. N Engl J Med. 1986: 315: 153-156. loop of Henle. Furosemide has little or no direct vascular 10. Kette F, Weil MH, Gazmuri RI. Bisera J, Rackow ECIntramyocardial effect, but it reduces venous and pulmonary vascular resis- hypercarbic acidosis during cardiac arrest and resuscitation. Crit Care tance through stimulation of local prostaglandin production Med.1993:21:901-906. 1. Adrogue H, Rashad MN, Gorin AB, Yacoub J, Madias NE. Arterio- and therefore may be very useful in the treatment of pulmo- nary edema. The vascular effects occur within 5 minutes Am J Physiol. 1989: 257- F1087-F1093 whereas diuresis is delayed. Although often used in acute 12. Tucker KJ. Idris AH. Wenzel V Orban D]. Changes in arterial and mixed renal failure to stimulate increased urine output, there is nous blood gases during untreated ventricular fibrillation and cardio- ulmonary resuscitation. Resuscitation. 1994: 28: 137-141 data to support this indication, and some data suggests an 13. Tang w. Weil MH. Sun S. Kette D. Gazmuri R. O Connell F. Bisera association with increased mortality. 72 The initial dose of J. Cardiopulmonary resuscitation by precordial compression but without furosemide is 0.5 to I mg/kg IV injected slowly mechanical ventilation. Am J Respir Crit Care Med. 1994: 150: 1709-1713 Newer"loop"diuretics that have an action similar to that 14. Gudipati CV, Weil MH, Gazmuri RI.Deshmukh HG,Bisera I.Rackow of furosemide and a similar profile of side effects include EC. Increases in coronary vein CO2 during cardiac resuscitation. J Appi torsemide and bumetanide. In patients who do not respond to high doses of loop diuretics alone, a combination of such 15. Capparelli EV, Chow Ms, Kluger J, Fieldman A Differences in systemic and myocardial blood acid-base status during cardiopulmonary resusci agents together with the administration of"proximal tubule tation. Crit Care Med. 1989: 17: 442-446 acting thiazide diuretics (such as chlorothiazide or meola- von Planta M, Weil MH, Gazmuri R. Bisera J, Rackow EC Myocardial zone) may be effective. Such combinations require close acidosis associated with Co2 production during cardiac arrest and resus citation. Circulation. 1989- 80: 684-692. observation with serial measurement of serum electrolytes to 17. Grundler w, Weil MH. Rackow EC. arteriovenous dioxide and avoid profound potassium depletion from their use. 1-1074 8. Sanders AB, Ewy GA, Taft TV. Resuscitation and blood gas Summary abnormalities during prolonged cardiopulmonary resuscitation. Ann Emerg Med.1984:13:676-679 Maintenance of adequate CPP is linked with survival follow- 19. Nowak RM. Martin GB, Carden dl, Tomlanovich MC. Selective ing CPR. Rescuers can support adequate CPP by providing hypercarbia during human CPR: implications regarding blood flow. Ann oppressions of adequate rate and depth, allowing full chest merg Med.1987;16:527-530 recoil after each compression, avoiding overventilation, and minimizing interruptions in chest compressions(see Part 4 Resuscitation and Emergency Cardiovascular Care: International Con- Adult Basic Life Support ). Exhaled CO2 can be a usefu sensus cience, Part 6: Advanced Cardiovascular Life Support: Section indicator of cardiac output produced by chest compressions. Devices to Assist Circulation. Circulation. 2000: 102(suppl I105-111. Pulse oximetry is not helpful during arrest, but it should be monitored in high-risk patients to ensure adequate oxygen- emergency department patients. Am J Emerg Med. 1988: 6: 549-554. tion. No medications have been shown to improve neurolog- 22. Bhende MS, Thompson AE. Evaluation of an end-tidal CO2 detector during pediatric cardiopulmonary resuscitation. Pediatrics. 1995: 95 ally intact survival from cardiac arrest. Better tools are needed to monitor effectiveness of CPr itation from end-tidal carbon dioxide concentration. Crit Care Med 199018:358-362 References 24. Grmec S, Klemen P. Does the end-tidal carbon dioxide (Etco2)concen- 1. Levine RL, Wayne MA, Miller CC. End-tidal carbon di outcome J Emerg med.2001;8:263-269 25. Grmec S, Kupnik D. Does the Mainz Emergency Evaluation Scoring 2. Wayne MA, Levine RL, Miller CC. Use of end-tidal carbon dioxide to (MEES) in combination with capnometry (MEESc)help in the prognosis redict outcome in prehospital cardiac arrest. Ann Emerg Med. 1995: 25 of outcome from cardiopulmonary resuscitation in a prehospital setting? Resuscitation. 2003: 58: 89-96
Sodium bicarbonate is not considered a first-line agent for the patient in cardiac arrest. When bicarbonate is used for special situations, an initial dose of 1 mEq/kg is typical. Whenever possible, bicarbonate therapy should be guided by the bicarbonate concentration or calculated base deficit obtained from blood gas analysis or laboratory measurement. To minimize the risk of iatrogenically induced alkalosis, providers should not attempt complete correction of the calculated base deficit. Other non–CO2-generating buffers such as Carbicarb, Tham, or Tribonat have shown potential for minimizing some adverse effects of sodium bicarbonate, including CO2 generation, hyperosmolarity, hypernatremia, hypoglycemia, intracellular acidosis, myocardial acidosis, and “overshoot” alkalosis.68–70 But clinical experience is greatly limited and outcome studies are lacking. Diuretics Furosemide is a potent diuretic agent that inhibits reabsorption of sodium in the proximal and distal renal tubule and the loop of Henle. Furosemide has little or no direct vascular effect, but it reduces venous and pulmonary vascular resistance through stimulation of local prostaglandin production71 and therefore may be very useful in the treatment of pulmonary edema. The vascular effects occur within 5 minutes, whereas diuresis is delayed. Although often used in acute renal failure to stimulate increased urine output, there is no data to support this indication, and some data suggests an association with increased mortality.72 The initial dose of furosemide is 0.5 to 1 mg/kg IV injected slowly. Newer “loop” diuretics that have an action similar to that of furosemide and a similar profile of side effects include torsemide and bumetanide. In patients who do not respond to high doses of loop diuretics alone, a combination of such agents together with the administration of “proximal tubule”– acting thiazide diuretics (such as chlorothiazide or metolazone) may be effective. Such combinations require close observation with serial measurement of serum electrolytes to avoid profound potassium depletion from their use. Summary Maintenance of adequate CPP is linked with survival following CPR. Rescuers can support adequate CPP by providing compressions of adequate rate and depth, allowing full chest recoil after each compression, avoiding overventilation, and minimizing interruptions in chest compressions (see Part 4: “Adult Basic Life Support”). Exhaled CO2 can be a useful indicator of cardiac output produced by chest compressions. Pulse oximetry is not helpful during arrest, but it should be monitored in high-risk patients to ensure adequate oxygenation. No medications have been shown to improve neurologically intact survival from cardiac arrest. Better tools are needed to monitor effectiveness of CPR. References 1. Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med. 1997;337: 301–306. 2. Wayne MA, Levine RL, Miller CC. Use of end-tidal carbon dioxide to predict outcome in prehospital cardiac arrest. Ann Emerg Med. 1995;25: 762–767. 3. Paradis NA, Martin GB, Rivers EP, Goetting MG, Appleton TJ, Feingold M, Nowak RM. Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA. 1990;263:1106–1113. 4. Halperin HR, Tsitlik JE, Gelfand M, Weisfeldt ML, Gruben KG, Levin HR, Rayburn BK, Chandra NC, Scott CJ, Kreps BJ, et al. A preliminary study of cardiopulmonary resuscitation by circumferential compression of the chest with use of a pneumatic vest. N Engl J Med. 1993;329:762–768. 5. Kern KB, Ewy GA, Voorhees WD, Babbs CF, Tacker WA. Myocardial perfusion pressure: a predictor of 24-hour survival during prolonged cardiac arrest in dogs. Resuscitation. 1988;16:241–250. 6. Lindner KH, Prengel AW, Pfenninger EG, Lindner IM, Strohmenger HU, Georgieff M, Lurie KG. Vasopressin improves vital organ blood flow during closed-chest cardiopulmonary resuscitation in pigs. Circulation. 1995;91:215–221. 7. Little CM, Angelos MG, Paradis NA. Compared to angiotensin II, epinephrine is associated with high myocardial blood flow following return of spontaneous circulation after cardiac arrest. Resuscitation. 2003;59: 353–359. 8. Connick M, Berg RA. Femoral venous pulsations during open-chest cardiac massage. Ann Emerg Med. 1994;24:1176–1179. 9. Weil MH, Rackow EC, Trevino R, Grundler W, Falk JL, Griffel MI. Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. N Engl J Med. 1986;315:153–156. 10. Kette F, Weil MH, Gazmuri RJ, Bisera J, Rackow EC. Intramyocardial hypercarbic acidosis during cardiac arrest and resuscitation. Crit Care Med. 1993;21:901–906. 11. Adrogue HJ, Rashad MN, Gorin AB, Yacoub J, Madias NE. Arteriovenous acid-base disparity in circulatory failure: studies on mechanism. Am J Physiol. 1989;257:F1087–F1093. 12. Tucker KJ, Idris AH, Wenzel V, Orban DJ. Changes in arterial and mixed venous blood gases during untreated ventricular fibrillation and cardiopulmonary resuscitation. Resuscitation. 1994;28:137–141. 13. Tang W, Weil MH, Sun S, Kette D, Gazmuri RJ, O’Connell F, Bisera J. Cardiopulmonary resuscitation by precordial compression but without mechanical ventilation. Am J Respir Crit Care Med. 1994;150: 1709–1713. 14. Gudipati CV, Weil MH, Gazmuri RJ, Deshmukh HG, Bisera J, Rackow EC. Increases in coronary vein CO2 during cardiac resuscitation. J Appl Physiol. 1990;68:1405–1408. 15. Capparelli EV, Chow MS, Kluger J, Fieldman A. Differences in systemic and myocardial blood acid-base status during cardiopulmonary resuscitation. Crit Care Med. 1989;17:442–446. 16. von Planta M, Weil MH, Gazmuri RJ, Bisera J, Rackow EC. Myocardial acidosis associated with CO2 production during cardiac arrest and resuscitation. Circulation. 1989;80:684–692. 17. Grundler W, Weil MH, Rackow EC. Arteriovenous carbon dioxide and pH gradients during cardiac arrest. Circulation. 1986;74:1071–1074. 18. Sanders AB, Ewy GA, Taft TV. Resuscitation and arterial blood gas abnormalities during prolonged cardiopulmonary resuscitation. Ann Emerg Med. 1984;13:676–679. 19. Nowak RM, Martin GB, Carden DL, Tomlanovich MC. Selective venous hypercarbia during human CPR: implications regarding blood flow. Ann Emerg Med. 1987;16:527–530. 20. American Heart Association in collaboration with International Liaison Committee on Resuscitation. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science, Part 6: Advanced Cardiovascular Life Support: Section 4: Devices to Assist Circulation. Circulation. 2000;102(suppl I):I105–I111. 21. Abraham E, Fink S. Conjunctival oxygen tension monitoring in emergency department patients. Am J Emerg Med. 1988;6:549–554. 22. Bhende MS, Thompson AE. Evaluation of an end-tidal CO2 detector during pediatric cardiopulmonary resuscitation. Pediatrics. 1995;95: 395–399. 23. Callaham M, Barton C. Prediction of outcome of cardiopulmonary resuscitation from end-tidal carbon dioxide concentration. Crit Care Med. 1990;18:358–362. 24. Grmec S, Klemen P. Does the end-tidal carbon dioxide (EtCO2) concentration have prognostic value during out-of-hospital cardiac arrest? Eur J Emerg Med. 2001;8:263–269. 25. Grmec S, Kupnik D. Does the Mainz Emergency Evaluation Scoring (MEES) in combination with capnometry (MEESc) help in the prognosis of outcome from cardiopulmonary resuscitation in a prehospital setting? Resuscitation. 2003;58:89–96. IV-82 Circulation December 13, 2005
Part 7. 4: Monitoring and Medications /v-8 26. Grmec s. Lah K. Tusek-Bunc K. Difference in end-tidal Co2 between 49. Edelson J, Stroshane R, Benziger DP, Cody R. Benotti J, Hood B Jr and ventricular fibrillation/pulseless ventricular Chatterjee K. Luczkowec C. Krebs C, Schwartz R. Pharmacokinetics tachycardia cardiac arrest in 27. Mauer D, Schneider T, Elich D, Dick W. Carbon dioxide levels during us standard cardio- The effectiveness of calcium chloride in refractory electromechanical pulmonary resuscitation Resuscitation. 1998: dissociation. Ann Emerg Med. 1985: 14: 626-629 28. Sanders AB, Ken KB, Otto CW, Milander MM, Ewy GA. End-tidal 51. Stueven H. Thompson BM, Aprahamian C. Darin JC. Use of calcium in prehospital cardiac arrest. Ann Emerg Med. 1983: 12: 136-139 nostic indicator for survival. JAMA. 1989- 262: 1347-1351 52. Ramoska EA, Spiller HA, Winter M, Borys D. A one-year evaluation of 29. Entholzner e. felt Mielke L auer B. hun- calcium channel blocker overdoses: toxicity and treatment. Ann Emerg delshausen VB. Hipp R. Assessment Med.1993:22:196-200 reanimation. Anasthesiol Intensrymed i Schmerzther MA. 1987. 53. Urban P, Scheidegger D, Buchmann B, Barth D. Cardiac arrest and blood ionized calcium levels. Ann Intern Med. 1988: 109: 110-113 30. Garnett AR, Ornato JP, Gonzalez ER, Johnson EB. End-tidal dioxide monitoring during cardiopulmonary resuscitation. JAMA Hypocalcemia in critically ill children. J Pediatr, 1989: 114: 946-951 257:512-515 31. Bhende Ms, Karasic DG, Karasic RB. End-tidal carbon dioxide changes 55. DiDomenico R, Park HY, Southworth MR, Eyrich HM, Lewis RK Finley JM, Schumock GT. Guidelines for acute decompensated heart during cardiopulmonary resuscitation after experimental asphyxial cardiac arrest. Am J Emerg Med. 1996: 14: 349-350 failure treatment. Ann Pharmacother. 2004: 38 56. Kirsten R. Nelson K. Kirsten D. Heintz B. Clin 32. Ahrens T, Schallom L, Bettorf K. Ellner S Hurt G, O'Mara V. Ludwi vasodilators. Part II. Clin Pharmacokinet. 1998 George W. Marino T, Shannon W. End-tidal carbon dioxide mea- surements as a prognostic indicator of outcome in cardiac arrest. Am J 57. Vaughan C, Delanty N. Hypertensive emergencies. Lancet. 2000:356 41-417 Crit Care.2001;10:391-398. 33. Cantineau JP, Lambert Y, Merckx P, Reynaud P, Porte F, Bertrand C, 18. Zerbe NF, Wagner BK. Use of vitamin B12 in the treatment and pre- Crit Care mec Duvaldestin P. End-tidal carbon dioxide during cardiopulmonary resus- citation in humans presenting mostly with asystole: a predictor of 59. Rindone JP, Sloane EP. Cyanide toxicity from sodium nitroprusside:risks 34. Kellum JA, Pinsky MR. Use of or agents in critically ill and management Published correction appears in Ann Phannacother. patients. Curr Opin Crir Care. 2002: 8: 236-241 199226:l160] Ann pharnacother.1992;26:515-519 35. Zaritsky AL. 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