Cardiogenic shock resident survival guide

Cardiogenic Shock Resident Survival Guide
Overview
Causes
FIRE
Emergency Revascularization
Diagnostic Criteria Cardiogenic Shock Acute Myocardial Infarction
Blood Pressure Maintenance
Hemodynamic Optimization

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The clinical definition of cardiogenic shock includes decreased cardiac output with evidence of tissue hypoxia in the presence of adequate intravascular volume.

Causes

Life Threatening Causes

Cardiogenic shock is a life-threatening condition and must be treated as such irrespective of the underlying cause.

Common Causes

• Arrhythmic

• Atrioventricular block
• Sinoatrial block
• Supraventricular tachycardia
• Ventricular tachycardia

• Mechanical

• Acute mitral regurgitation (papillary muscle rupture, chordae tendinae rupture)
• Free wall rupture
• Hypertrophic cardiomyopathy
• Obstruction to left ventricular filling (mitral stenosis, left atrial myxoma)
• Obstruction to left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy)
• Ventricular septal defect

• Myopathic

• Cardiomyopathy
• Myocardial contusion
• Myocardial infarction
• Myocarditis
• Myxedema coma
• Postischemic myocardial stunning
• Septic myocardial depression

• Pharmacologic

• Anthracyclines
• Calcium channel blockers

Click here for the complete list of causes.

FIRE: Focused Initial Rapid Evaluation

Focused Initial Rapid Evaluation (FIRE) should be undertaken to identify patients requiring urgent intervention.

Abbreviations: CBC, complete blood count; CI, cardiac index; CK-MB, creatine kinase MB isoform; CVP, central venous pressure; DC, differential count; ICU, intensive care unit; INR, international normalized ratio; LFT, liver function test; MAP, mean arterial pressure; PCWP, pulmonary capillary wedge pressure; PT, prothrombin time; PTT, partial prothrombin time; SaO2, arterial oxygen saturation; SBP, systolic blood pressure; ScvO2, central venous oxygen saturation; SvO2, mixed venous oxygen saturation; SMA-7, sequential multiple analysis-7.

Does the patient have cardinal findings that increase the pretest probability of cardiogenic shock? ❑  Evidence of end-organ hypoperfusion ❑  Altered mental status ❑  Cold extremities ❑  Cyanosis ❑  Oliguria (urine output <0.5 mL/kg/h) ❑  Sustained hypotension (≥30 min) ❑  SBP <90 mm Hg or ❑  MAP ↓ >30 mm Hg below baseline ❑  Presence of myocardial dysfunction after exclusion or correction of non-myocardial factors contributing to tissue hypoperfusion

YES

NO

Cardiogenic shock suspected (click for details on criteria)

Proceed to shock resident survival guide

Immediate steps

Initial management ❑  Oxygen ± ventilatory support ❑  ECG monitor ❑  Pulse oximeter ❑  Sphygmomanometer or arterial line ❑  Large-bore peripheral venous lines ❑  Central venous catheter ❑  Bladder catheterization ❑  Hold antihypertensive medications ❑  ± Correct tachy- or bradyarrhythmia

Initial workup ❑  Arterial blood gas ❑  CBC/DC/SMA-7/LFT/PT/PTT/INR ❑  Cardiac troponins, CK-MB ❑  BNP, NT-proBNP ❑  Lactate ❑  12-Lead ECG ❑  Chest radiograph ❑  Echocardiography

Maintain adequate blood pressure (click for details)

SBP <70 mm Hg: ❑  Norepinephrine ❑  Initial dose: 0.5–1.0 μg/min ❑  Maximum dose: 30–40 μg/min ❑  Titrate to SBP >90 mm Hg SBP 70–100 mm Hg with symptoms: ❑  Dopamine ❑  Cardiac dose: 5.0–10 μg/kg/min ❑  Pressor dose: 10–20 μg/kg/min ❑  Maximum dose: 20–50 μg/kg/min SBP 70–100 mm Hg w/o symptoms: ❑  Dobutamine ❑  Usual dose: 2.0–20 μg/kg/min ❑  Maximum dose: 40 μg/kg/min ❑  Avoid ↑ HR by >10% of baseline SBP >100 mm Hg: ❑  Nitroglycerin ❑  Initial dose: 5.0 μg/min ❑  Titrate by 10–20 μg/min q 3–5 min ❑  Nitroprusside ❑  Initial dose: 0.3 μg/kg/min ❑  Usual dose: 3.0–5.0 μg/kg/min ❑  Maximum dose: 10 μg/kg/min

Acute coronary syndrome likely? (click for details on criteria)

❑  New ischemic ECG changes ❑  Positive cTnT, cTnI, or CK-MB ❑  Anginal pain

YES

NO

Proceed to Emergency Revascularization

❑  ICU admission ❑  Swan-Ganz catheter ❑  Cardiology consultation

Optimize hemodynamic status (click for details)

Preload Goal: PCWP 15–18 mm Hg, CVP 8–12 cm H2O ❑  Fluid challenge protocol ("TROL") ❑  ± Correct pulmonary congestion ❑  Furosemide ❑  Usual dose: 40 mg slow IV injection ❑  May increase dose to 80 mg after 1 hour as needed ❑  Morphine ❑  Usual dose: 2–4 mg slow IV injection ❑  May repeat dose every 5–30 minutes as needed

Afterload Goal: MAP >65 mm Hg, SVR 800–1200 dyn·s·cm−5 ❑  If ↑ MAP & ↑ SVR: ❑  Taper vasopressor ❑  ± Vasodilator ❑  Nitroglycerin ❑  Initial dose: 5.0 μg/min ❑  Titrate by 10–20 μg/min q 3–5 min ❑  Nitroprusside ❑  Initial dose: 0.3 μg/kg/min ❑  Usual dose: 3.0–5.0 μg/kg/min ❑  Maximum dose: 10 μg/kg/min ❑  If ↓ MAP & ↓ SVR: ❑  Vasopressor ❑  Norepinephrine ❑  Initial dose: 0.5–1.0 μg/min ❑  Maximum dose: 30–40 μg/min ❑  Titrate to SBP >90 mm Hg ❑  Dopamine ❑  Cardiac dose: 5.0–10 μg/kg/min ❑  Pressor dose: 10–20 μg/kg/min ❑  Maximum dose: 20–50 μg/kg/min ❑  Phenylephrine ❑  Initial dose: 100–180 μg/min ❑  Maintenance dose: 40–60 μg/min ❑  ± Vasopressin ❑  Adjunctive therapy to norepinephrine or dopamine ❑  Usual dose: 0.01–0.03 U/min ❑  Maximum dose: 0.04 U/min ❑  If ↓ MAP & ↑ SVR: ❑  Continue vasopressor ❑  Optimize cardiac output with inotropic agent

Cardiac index Goal: CI >2.2 L/min/m2 ❑  Dobutamine ❑  Usual dose: 2.0–20 μg/kg/min ❑  Maximum dose: 40 μg/kg/min ❑  Avoid ↑ HR by >10% of baseline ❑  Milrinone ❑  Loading dose: 50 μg/kg (slowly over 10 minutes) ❑  Maintenance dose: 0.375–0.75 μg/kg/min

Evaluate perfusion and oxygenation

Endpoints: ❑  SaO2 >92% ❑  SvO2 >60% ❑  ScvO2 >70% ❑  Urine output >0.5 mL/kg/h ❑  Lactate <2.2 mM/L ❑  Hematocrit ≥30%

If hypoperfusion persists: ❑  Consider IABP, VAD, or ECMO if indicated

Emergency Revascularization [Return to FIRE]

Acute coronary syndrome (click for details on criteria)

❑  New ischemic ECG changes ❑  New or presumably new ST elevation at the J point in two contiguous leads with the cutoff points: ❑  ≥0.1 mV in all leads other than leads V2–V3 ❑  ≥0.15 mV in women in leads V2–V3 ❑  ≥0.2 mV in men ≥40 years in leads V2–V3 ❑  ≥0.25 mV in men <40 years in leads V2–V3 ❑  New left bundle branch block ❑  QRS duration ≥120 ms ❑  Supraventricular rhythm ❑  Absence of WPW pattern ❑  Broad and notched or slurred R in I and V5 or V6 ❑  Absence of Q wave in I and V5 and V6 ❑  R peak times ≥60 ms in V5 or V6 ❑  New or presumably new ST-segment–T wave changes ❑  Horizontal or down-sloping ST depression ≥0.05 mV in two contiguous leads ❑  T inversion ≥0.1 mV in two contiguous leads with prominent R wave or R/S ratio >1 ❑  Positive cardiac biomarkers (cTnT, cTnI, or CK-MB) ❑  Anginal pain ST elevation in contiguous leads and location of MI and coronary occlusion ECG Leads with STE Location of MI Location of Coronary Occlusion I, aVL Lateral, Apical Diagonal, Obtuse Marginal, Distal LAD II, III, aVF Inferior PDA, Wraparound LAD V1, V2 Septal Proximal LAD, Septal Perforators V3, V4 Anterior Proximal or Mid LAD, Diagonal V5, V6 Lateral, Apical Diagonal, Obtuse Marginal, Distal LAD V7, V8, V9 Posterobasal LCx, RCA V3R, V4R RV Free Wall Proximal RCA

STEMI

UA/NSTEMI

Diagnostic Criteria [Return to FIRE]

Criteria for Cardiogenic Shock

• Clinical Criteria

• Sustained hypotension (SBP <90 mm Hg or MAP 30 mm Hg below baseline in preexisting hypertension for at least 30 minutes)
• Evidence of tissue hypoperfusion (such as oliguria, cyanosis, cool extremities, and altered mental status)
• Presence of myocardial dysfunction after exclusion or correction of non-myocardial factors contributing to tissue hypoperfusion (such as hypovolemia, hypoxia, and acidosis)

• Hemodynamic Criteria

• Sustained hypotension (SBP <90 mm Hg or MAP 30 mm Hg below baseline in preexisting hypertension for at least 30 minutes)
• Depressed cardiac index (<1.8 L/min/m² of BSA without support or <2.0–2.2 L/min/m² of BSA with support) in the presence of an elevated wedge pressure (>15 mm Hg).

Criteria for Acute Myocardial Infarction

The term acute myocardial infarction (MI) should be used when there is evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia. Under these conditions any one of the following criteria meets the diagnosis for MI:

• Detection of a rise and/or fall of cardiac biomarker values (preferably cardiac troponin) with at least one value above the 99^th percentile upper reference limit (URL) and with at least one of the following:

• Symptoms of ischemia

• Recent episode of typical ischemic discomfort that either is of new onset or is severe or that exhibits an accelerating pattern of previous stable angina (especially if it has occurred at rest or is within 2 weeks of a previously documented MI)
• Quality: squeezing, grip-like, pressure-like, suffocating, crushing, or heavy
• Location: diffuse, not localized, nor positional, nor affected by movement at substernal area ± radiation to the neck, jaw, epigastrium, shoulders, or arms
• Duration: usually >20 minutes
• Factors that provoke the pain: exertion or emotional stress
• Factors that relieve the pain: rest or sublingual nitroglycerin (usually within minutes)
• Accompanying symptoms: diaphoresis, nausea or syncope

• New or presumably new significant ST-segment–T wave changes or new left bundle branch block (LBBB).
• Development of pathological Q waves in the ECG.
• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.
• Identification of an intracoronary thrombus by angiography or autopsy.

• Cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG changes or new LBBB, but death occurred before cardiac biomarkers were obtained, or before cardiac biomarker values would be increased.

• Percutaneous coronary intervention related MI is arbitrarily defined by elevation of cardiac troponin (cTn) values (>5 × 99^th percentile URL) in patients with normal baseline values (≤99^th percentile URL) or a rise of cTn values >20% if the baseline values are elevated and are stable or falling. In addition, either one of the followings is required:

• Symptoms suggestive of myocardial ischemia
• New ischemic ECG changes
• Angiographic findings consistent with a procedural complication
• Imaging demonstration of new loss of viable myocardium or new regional wall motion abnormality

• Stent thrombosis associated with MI when detected by coronary angiography or autopsy in the setting of myocardial ischemia and with a rise and/or fall of cardiac biomarker values with at least one value above the 99^th percentile URL.

• Coronary artery bypass grafting related MI is arbitrarily defined by elevation of cardiac biomarker values (>10 × 99^th percentile URL) in patients with normal baseline cTn values (≤99^th percentile URL). In addition, either one of the followings is required:

• New pathological Q waves or new LBBB
• Angiographic documented new graft or new native coronary artery occlusion
• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality

Maintenance of Blood Pressure [Return to FIRE]

Norepinephrine

• Dosage and Administration

• Suggested Dilution:

• Mix 4 mg of norepinephrine in 250 mL of D5W or D5NS. Avoid dilution in normal saline alone.

• Suggested Regimen:

• Start at a dose of 0.5–1.0 μg/min IV infusion; titrate to maintain SBP at above 90 mm Hg (up to 30–40 μg/min).

• Contraindications

• Norepinephrine should not be given to patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed.
• Norepinephrine should also not be given to patients with mesenteric or peripheral vascular thrombosis unless it is necessary as a life-saving procedure.

Dopamine

• Dosage and Administration

• Suggested Dilution: transfer contents of one or more ampuls or vials by aseptic technique to either 250 mL or 500 mL of one of the following sterile intravenous solutions

• Sodium Chloride Injection
• Dextrose (5%) Injection
• Dextrose (5%) and Sodium Chloride (0.9%) Injection
• 5% Dextrose in 0.45% Sodium Chloride Solution
• Dextrose (5%) in Lactated Ringer’s Solution
• Sodium Lactate (1/6 Molar) Injection
• Lactated Ringer’s Injection

• Suggested Regimen:

• Begin administration of diluted solution at doses of 2–5 μg/kg/minute in patients who are likely to respond to modest increments of heart force and renal perfusion.
• In more seriously ill patients, begin administration of diluted solution at doses of 5 μg/kg/minute and increase gradually, using 5–10 μg/kg/minute increments, up to 20–50 μg/kg/minute as needed.
• If doses of 50 μg/kg/minute are required, it is suggested that urine output be checked frequently. Should the urine flow begin to decrease in the absence of hypotension, reduction of dosage should be considered.
• Treatment of all patients requires constant evaluation of therapy in terms of the blood volume, augmentation of myocardial contractility, and distribution of peripheral perfusion. Dosage should be adjusted according to the patient’s response, with particular attention to diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias as indices for decreasing or temporarily suspending the dosage.

• Contraindications

• Pheochromocytoma
• Uncorrected tachyarrhythmias or ventricular fibrillation

Dobutamine

• Dosage and Administration

• Suggested Dilution: dobutamine injection must be further diluted in an IV container. Dilute 20 mL of dobutamine in at least 50 mL of diluent and dilute 40 mL of dobutamine in at least 100 mL of diluent. Use one of the following intravenous solutions as a diluent:

• Dextrose Injection 5%
• Dextrose 5% and Sodium Chloride 0.45% Injection
• Dextrose 5% and Sodium Chloride 0.9% Injection
• Dextrose Injection 10%, Isolyte® M with 5% Dextrose Injection
• Lactated Ringer’s Injection
• 5% Dextrose in Lactated Ringer’s Injection
• Normosol®-M in D5-W
• 20% Osmitrol® in Water for Injection
• Sodium Chloride Injection 0.9%
• Sodium Lactate Injection

• Suggested Regimen:

• The rate of infusion needed to increase cardiac output usually ranged from 2.5 to 15 mcg/kg/min.
• On rare occasions, infusion rates up to 40 mcg/kg/min have been required to obtain the desired effect.

• Contraindications

• Idiopathic hypertrophic subaortic stenosis
• Hypersensitivity to dobutamine

Nitroglycerin

• Dosage and Administration

• Suggested Initial Dilution:

• Nitroglycerin must be diluted in dextrose (5%) injection or sodium chloride (0.9%) injection prior to its infusion. Transfer 50 mg of nitroglycerin into a 500 mL glass bottle of either dextrose (5%) injection or sodium chloride injection (0.9%). This yields a final concentration of 100 μg/mL. Diluting 5 mg nitroglycerin into 100 mL will yield a final concentration of 50 μg/mL.

• Suggested Maintenance Dilution:

• Consider the fluid requirements of the patient as well as the expected duration of infusion in selecting the appropriate dilution of Nitroglycerin Injection.
• The concentration of nitroglycerin should not exceed 400 μg/mL.

• Suggested Regimen:

• Severe hypotension and shock may occur with even small doses of nitroglycerin. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris.
• The initial dosage should be 5 μg/min delivered through an infusion pump. Subsequent titration must be adjusted to the clinical situation, with dose increments becoming more cautious as partial response is seen.
• Initial titration should be in 5 μg/min increments, with increases every 3–5 minutes until some response is noted.
• If no response is seen at 20 μg/min, increments of 10 and later 20 μg/min can be used.
• Once a partial blood pressure response is observed, the dose increase should be reduced and the interval between increases should be lengthened.

• Contraindications

• Pericardial tamponade
• Restrictive cardiomyopathy
• Constrictive pericarditis
• Hypersensitivity to nitroglycerin

Nitroprusside

• Dosage and Administration

• Suggested Dilution:

• Depending on the desired concentration, the solution containing 50 mg of nitroprusside must be further diluted in 250–1000 mL of sterile 5% dextrose injection.

• Suggested Regimen:

• While the average effective rate in adult and pediatric patients is about 3 μg/kg/min, some patients will become dangerously hypotensive at this rate.
• Nitroprusside can induce essentially unlimited blood pressure reduction, the blood pressure must be continuously monitored, using either a continually reinflated sphygmomanometer or (preferably) an intra-arterial pressure sensor. Special caution should be used in elderly patients, since they may be more sensitive to the hypotensive effects of the drug.
• Infusion of sodium nitroprusside should be started at a very low rate (0.3 μg/kg/min), with upward titration every few minutes until the desired effect is achieved or the maximum recommended infusion rate (10 μg/kg/min) has been reached.

• Contraindications

• Sodium nitroprusside should not be used for the treatment of acute congestive heart failure associated with reduced peripheral vascular resistance such as high-output heart failure that may be seen in endotoxic sepsis.
• Sodium nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or arteriovenous shunting.
• Sodium nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation, or in moribund patients coming to emergency surgery.
• Patients with congenital (Leber’s) optic atrophy or with toxic amblyopia have unusually high cyanide/thiocyanate ratios. These rare conditions are probably associated with defective or absent rhodanase, and sodium nitroprusside should be avoided in these patients.

Optimization of Hemodynamic Status [Return to FIRE]

Preload Optimization

Fluid Challenge Protocol

• Preload optimization involves scrupulous fluid loading, manipulation of PCWP and/or CVP levels, and correction of pulmonary congestion.

• Protocolized fluid administration titrated to hemodynamic and clinical endpoints secures the efficacy of tissue perfusion and oxygenation.

• Four elements of the fluid challenge protocol: type of fluid (T), rate of fluid administration (R), objective (O), and limits (L).

• 1. Type of fluid (T)

• The choice of crystalloid or colloid solution should be made on the basis of the underlying disease, the nature of fluid deficit, the severity of circulatory failure, the serum albumin concentration, and the risk of bleeding.
• There were no significant differences in mortality between saline and albumin infusion for critically ill patients.
• Blood transfusion may be considered in the presence of profound anemia or massive hemorrhage.
• Hyperchloremic acidosis may be associated with the use of isotonic saline solution.

• 2. Rate of fluid administration (R)

• Based on the level of pulmonary capillary wedge pressure or central venous pressure, a volume of 50, 100, or 200 ml of fluid is administered over a 10-minute interval through a peripheral venous catheter.

Baseline PCWP (mm Hg) Baseline CVP (cm H2O) Rate of fluid administration ≥16 ≥14 50 mL over 10 minutes <16 but ≥12 <14 but ≥8 100 mL over 10 minutes <12 <8 200 mL over 10 minutes

• 3. Objective (O)

• Fluid administration should be titrated to reach predetermined clinical endpoints such as resolution of tachycardia or oliguria, improved skin perfusion or level of consciousness, normalization of lactate concentrations, and restoration of adequate blood pressure or ventricular filling pressure.

• 4. Limits (L)

• Fluid administration should be stopped if the safety limits are violated to minimize the risk of developing pulmonary edema.
• Inotropes, vasodilators, or mechanical circulatory device may be required if signs of hypoperfusion persist despite optimal fluid loading.
• Hemodynamic safety limits based on PCWP (the 7–3 rule) or CVP (the 5–2 rule):

↑ PCWP (mm Hg) ↑ CVP (cm H2O) Action ≥7 ≥5 Stop fluid administration <7 but >3 <5 but >2 Wait and recheck pressure after 10 minutes ≤3 ≤2 Continue fluid administration

Pulmonary Congestion

• Findings suggestive of cardiogenic pulmonary edema:

• History and clinical manifestations

• Cough
• Dyspnea
• Expectoration of frothy sputum
• Orthopnea
• Paroxysmal nocturnal dyspnea
• Signs and symptoms of heart failure
• Signs and symptoms of hypoxemia
• Signs and symptoms of myocardial ischemia
• Signs and symptoms of valvular dysfunction
• Tachypnea

• Physical examination

• Cool extremities
• Heart murmurs
• Hepatomegaly
• Inspiratory crackles or rhonchi
• Jugular venous distention
• S3 gallop
• Peripheral edema

• Laboratory and hemodynamic findings

• BNP > 500 pg/mL
• PCWP >18 mm Hg

• Radiologic findings

• Central infiltrates with peripheral sparing
• Cephalization of pulmonary vessels
• Enlarged cardiac silhouette
• Enlargement of peribronchovascular spaces
• Increased opacity of acinar areas that coalesce into frank consolidations
• Kerley B lines
• Peribronchial cuffing
• Pleural effusions
• Vascular pedicle width >70 mm

• Radiologic manifestations of pulmonary congestion reflect the extent of elevation in wedge pressure:

PCWP (mm Hg) Phase of Pulmonary Congestion Findings on Chest Radiograph 18–20 Onset of pulmonary congestion Redistribution of pulmonary flow to the upper lobes ("cephalization") and Kerley lines 20–25 Moderate congestion Diminished clarity of the borders of medium-sized pulmonary vessels ("perihilar haze") 25–30 Severe congestion Radiolucent grapelike clusters surrounded by radiodense fluid ("periacinar rosette") >30 Onset of pulmonary edema Coalescence of periacinar rosettes resulting in "Bat's wing" opacities

Furosemide

• Dosage and Administration

• For acute pulmonary edema, the initial dose is 40 mg injected slowly intravenously (over 1 to 2 minutes).
• If a satisfactory response does not occur within 1 hour, the dose may be increased to 80 mg injected slowly intravenously (over 1 to 2 minutes).

• Contraindications

• Anuria
• Hypersensitivity to furosemide

Morphine

• Dosage and Administration

• Morphine may cause respiratory depression or exacerbate hypotension in volume-depleted patients.
• Morphine may be used adjunctively in the treatment of acute pulmonary edema at a dose of 2–4 mg (slow IV injection over 1–5 minutes) every 5–30 minutes as needed.

• Contraindications

• Hypersensitivity to morphine sulfate is one of the contraindications to its use.
• Morphine should not be used in convulsive states, such as those occurring in status epilepticus, tetanus, and strychnine poisoning.
• Morphine is also contraindicated in the following conditions: respiratory insufficiency or depression; bronchial asthma; heart failure secondary to chronic lung disease; cardiac arrhythmias; increased intracranial or cerebrospinal pressure; head injuries; brain tumor; acute alcoholism; and delirium tremens.

Afterload Optimization

Nitroglycerin

• Dosage and Administration

• Suggested Initial Dilution:

• Nitroglycerin must be diluted in dextrose (5%) injection or sodium chloride (0.9%) injection prior to its infusion. Transfer 50 mg of nitroglycerin into a 500 mL glass bottle of either dextrose (5%) injection or sodium chloride injection (0.9%). This yields a final concentration of 100 μg/mL. Diluting 5 mg nitroglycerin into 100 mL will yield a final concentration of 50 μg/mL.

• Suggested Maintenance Dilution:

• Consider the fluid requirements of the patient as well as the expected duration of infusion in selecting the appropriate dilution of Nitroglycerin Injection.
• The concentration of nitroglycerin should not exceed 400 μg/mL.

• Suggested Regimen:

• Severe hypotension and shock may occur with even small doses of nitroglycerin. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris.
• The initial dosage should be 5 μg/min delivered through an infusion pump. Subsequent titration must be adjusted to the clinical situation, with dose increments becoming more cautious as partial response is seen.
• Initial titration should be in 5 μg/min increments, with increases every 3–5 minutes until some response is noted.
• If no response is seen at 20 μg/min, increments of 10 and later 20 μg/min can be used.
• Once a partial blood pressure response is observed, the dose increase should be reduced and the interval between increases should be lengthened.

• Contraindications

• Pericardial tamponade
• Restrictive cardiomyopathy
• Constrictive pericarditis
• Hypersensitivity to nitroglycerin

Nitroprusside

• Dosage and Administration

• Suggested Dilution:

• Depending on the desired concentration, the solution containing 50 mg of nitroprusside must be further diluted in 250–1000 mL of sterile 5% dextrose injection.

• Suggested Regimen:

• While the average effective rate in adult and pediatric patients is about 3 μg/kg/min, some patients will become dangerously hypotensive at this rate.
• Nitroprusside can induce essentially unlimited blood pressure reduction, the blood pressure must be continuously monitored, using either a continually reinflated sphygmomanometer or (preferably) an intra-arterial pressure sensor. Special caution should be used in elderly patients, since they may be more sensitive to the hypotensive effects of the drug.
• Infusion of sodium nitroprusside should be started at a very low rate (0.3 μg/kg/min), with upward titration every few minutes until the desired effect is achieved or the maximum recommended infusion rate (10 μg/kg/min) has been reached.

• Contraindications

• Sodium nitroprusside should not be used for the treatment of acute congestive heart failure associated with reduced peripheral vascular resistance such as high-output heart failure that may be seen in endotoxic sepsis.
• Sodium nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or arteriovenous shunting.
• Sodium nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation, or in moribund patients coming to emergency surgery.
• Patients with congenital (Leber’s) optic atrophy or with toxic amblyopia have unusually high cyanide/thiocyanate ratios. These rare conditions are probably associated with defective or absent rhodanase, and sodium nitroprusside should be avoided in these patients.

Norepinephrine

• Dosage and Administration

• Suggested Dilution:

• Mix 4 mg of norepinephrine in 250 mL of D5W or D5NS. Avoid dilution in normal saline alone.

• Suggested Regimen:

• Start at a dose of 0.5–1.0 μg/min IV infusion; titrate to maintain SBP at above 90 mm Hg (up to 30–40 μg/min).

• Contraindications

• Norepinephrine should not be given to patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed.
• Norepinephrine should also not be given to patients with mesenteric or peripheral vascular thrombosis unless it is necessary as a life-saving procedure.

Dopamine

• Dosage and Administration

• Suggested Dilution: transfer contents of one or more ampuls or vials by aseptic technique to either 250 mL or 500 mL of one of the following sterile intravenous solutions

• Sodium Chloride Injection
• Dextrose (5%) Injection
• Dextrose (5%) and Sodium Chloride (0.9%) Injection
• 5% Dextrose in 0.45% Sodium Chloride Solution
• Dextrose (5%) in Lactated Ringer’s Solution
• Sodium Lactate (1/6 Molar) Injection
• Lactated Ringer’s Injection

• Suggested Regimen:

• Begin administration of diluted solution at doses of 2–5 μg/kg/minute in patients who are likely to respond to modest increments of heart force and renal perfusion.
• In more seriously ill patients, begin administration of diluted solution at doses of 5 μg/kg/minute and increase gradually, using 5–10 μg/kg/minute increments, up to 20–50 μg/kg/minute as needed.
• If doses of 50 μg/kg/minute are required, it is suggested that urine output be checked frequently. Should the urine flow begin to decrease in the absence of hypotension, reduction of dosage should be considered.
• Treatment of all patients requires constant evaluation of therapy in terms of the blood volume, augmentation of myocardial contractility, and distribution of peripheral perfusion. Dosage should be adjusted according to the patient’s response, with particular attention to diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias as indices for decreasing or temporarily suspending the dosage.

• Contraindications

• Pheochromocytoma
• Uncorrected tachyarrhythmias or ventricular fibrillation

Phenylephrine

• Dosage and Administration

• Suggested Dilution:

• Add 10 mg of the drug (1 mL of 1 percent solution) to 500 mL of Dextrose Injection or Sodium Chloride Injection (providing a 1:50,000 solution).

• Suggested Regimen:

• To raise the blood pressure rapidly, start the infusion at about 100 μg to 180 μg per minute (based on 20 drops per mL this would be 100 to 180 drops per minute).
• When the blood pressure is stabilized (at a low normal level for the individual), a maintenance rate of 40 μg to 60 μg per minute usually suffices (based on 20 drops per mL this would be 40 to 60 drops per minute).
• If a prompt initial pressor response is not obtained, additional increments of phenylephrine (10 mg or more) are added to the infusion bottle. The rate of flow is then adjusted until the desired blood pressure level is obtained.

• Contraindications

• Severe hypertension
• Ventricular tachycardia
• Hypersensitivity to phenylephrine

Vasopressin

• Dosage and Administration

• Suggested Regimen:

• Adjunctive use of a low dose of vasopressin (0.01–0.04 U/min) to catecholamine may reduce its dosage requirement in patients with refractory shock.

• Contraindications

• Anaphylaxis or hypersensitivity to the drug or its components

Cardiac Output Optimization

Dobutamine

• Dosage and Administration

• Suggested Dilution: dobutamine injection must be further diluted in an IV container. Dilute 20 mL of dobutamine in at least 50 mL of diluent and dilute 40 mL of dobutamine in at least 100 mL of diluent. Use one of the following intravenous solutions as a diluent:

• Dextrose Injection 5%
• Dextrose 5% and Sodium Chloride 0.45% Injection
• Dextrose 5% and Sodium Chloride 0.9% Injection
• Dextrose Injection 10%, Isolyte® M with 5% Dextrose Injection
• Lactated Ringer’s Injection
• 5% Dextrose in Lactated Ringer’s Injection
• Normosol®-M in D5-W
• 20% Osmitrol® in Water for Injection
• Sodium Chloride Injection 0.9%
• Sodium Lactate Injection

• Suggested Regimen:

• The rate of infusion needed to increase cardiac output usually ranged from 2.5–15 mcg/kg/min.
• On rare occasions, infusion rates up to 40 mcg/kg/min have been required to obtain the desired effect.

• Contraindications

• Idiopathic hypertrophic subaortic stenosis
• Hypersensitivity to dobutamine

Milrinone

• Dosage and Administration

• Suggested Regimen:

• Milrinone should be administered with a loading dose followed by a continuous infusion (maintenance dose).
• Loading dose: 50 μg/kg (slowly over 10 minutes)
• Maintenance dose: 0.50 μg/kg/min (0.375–0.75 μg/kg/min)

• Contraindications

• Hypersensitivity to milrinone

References