ATS CORE CURRICULUM ATS Core Curriculum 2014: Part II. Adult Critical Care Medicine Series Editor: Carey Thomson Part II Editor: Jason Poston Peter D. Sottile1, Marc Moss1, Jayshil J. Patel2, Jonathon D. Truwit2, Maryam Sheikh3, Janice L. Zimmerman4, Amit Diwakar5, Gregory A. Schmidt5, Gregory T. Means6, Jason N. Katz7, Akshay S. Desai8, Neil R. MacIntyre9, and Jason T. Poston10 1

Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, University of Colorado, Denver, Colorado; 2Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; 3Mercy Critical Care Medicine, Mercy St. Louis, St. Louis, Missouri; 4Critical Care Division, Department of Medicine, Houston Methodist, Houston, Texas; 5Division of Pulmonary Diseases, Critical Care, and Occupational Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa; 6Department of Medicine, and 7Divisions of Cardiology and Pulmonary and Critical Care Medicine, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina; 8Cardiovascular Medicine Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; 9Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina; and 10Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, Illinois Keywords: acute respiratory distress syndrome; drug overdose; heart failure; monitoring, physiologic; pulmonary disease, chronic obstructive

Acute Respiratory Distress Syndrome Peter D. Sottile and Marc Moss In 1994, the American-European Consensus Conference developed diagnostic criteria in an attempt to achieve a uniform definition of the Acute Respiratory Distress Syndrome (ARDS). The 2012 Berlin Definition refined these diagnostic criteria for ARDS. Important differences in the new definition include: (1) the removal of the term acute lung injury and the addition of three ARDS categories—mild, moderate, and severe—to stratify severity; (2) inclusion of a minimal amount of positive end-expiratory pressure (PEEP) or continuous positive airway pressure; (3) the necessity of respiratory failure developing within 1 week of the primary clinical insult; (4) removal of diagnostic criteria based on the pulmonary capillary occlusion pressure; and (5) no requirement for mechanical ventilation in patients with mild ARDS (1). Limiting ventilator-induced lung injury has become one of the primary goals of caring for patients with ARDS. Because ARDS decreases recruitable lung volume, lung-protective ventilation should be implemented to minimize alveolar overdistention (volutrauma and barotrauma) and decrease the repetitive shear stress from alveolar closing (atelectrauma). Mechanical ventilation using tidal volumes of 6 ml/kg predicted body weight to prevent plateau pressures (Pplat) greater than 30 cm H2O has been demonstrated to increase the number of ventilator-free days and decrease mortality (2).

More recently, adjunctive strategies have been reported to benefit patients with severe ARDS. Neuromuscular blockade is hypothesized to improve ventilator dyssynchrony, thus decreasing ventilator-induced lung injury. Moreover, neuromuscular blockade decreases the work of breathing and metabolic demand, improving oxygen use. In patients with a PaO2:FIO2 ratio of less than 150 mm Hg, the use of neuromuscular blockade for 48 hours improves oxygenation, increases ventilator-free days, and improves adjusted 90-day survival (3, 4). By improving ventilation/perfusion mismatching, prone positioning has been used to improve oxygenation in patients with ARDS. However, early studies failed to demonstrate an improvement in mortality likely due to enrolling patients with less severe ARDS and the relatively limited time that was required in the prone position (5, 6). A recent trial (Proning Severe ARDS Patients [PROSEVA] Study Group) of patients with severe ARDS demonstrated that prone positioning does indeed increase ventilator-free days and, importantly, decrease mortality (90-d mortality: 24 vs. 41%; hazard ratio, 0.44 (95% confidence interval, 0.29–0.67) (7). Compared with prior studies, PROSEVA enrolled patients with more severe ARDS (PaO2:FIO2 ratio , 150 mm Hg), and the patients remained in the prone position for at least 16 hours per day. These results suggest that the improved mortality in severe ARDS is in part from being in the prone position for prolonged periods. As the mortality of patients with ARDS continues to decrease, there are an increasing number of ARDS survivors. The long-term

(Received in original form July 19, 2014; accepted in final form August 27, 2014 ) The American Thoracic Society CORE Curriculum updates clinicians annually in adult and pediatric pulmonary diseases, medical critical care, and sleep medicine in a 3-year recurring cycle of topics. The 2014 course was presented in May during the annual International Conference and is published monthly in four parts beginning with the September issue of the journal. Part II covers advances in adult critical care medicine. An ABIM Maintenance of Certification (MOC) module covering the contents of the CORE Curriculum can be accessed online at: http://www.atsjournals.org/page/ats_core_curriculum_2014, and a Continuing Medical Education (CME) exercise is available at www.atsjournals.org. Correspondence and requests for reprints should be addressed to Jason Poston, M.D., 5841 South Maryland Avenue, University of Chicago Medicine, Chicago, IL 60637. E-mail: [email protected] Ann Am Thorac Soc Vol 11, No 8, pp 1307–1315, Oct 2014 Copyright © 2014 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201407-322CME Internet address: www.atsjournals.org

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ATS CORE CURRICULUM morbidity of these patients remains significant. In a longitudinal study of previously healthy ARDS survivors, patients continue to report exercise limitation and reduced quality of life 5 years after hospital discharge. Despite normalization of spirometry in more than 75% of ARDS survivors, 6-minute-walk tests remained decreased when compared with age-matched control subjects. Additionally, survivors have increased rates of depression, anxiety, and post-traumatic stress disorder. ARDS survivors often delay their reentry to the work force, although most begin working within 2 years of their illness (8) (Table 1).

References 1 ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition; JAMA 2012;307:2526–2533. 2 The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301–1308. 3 Gainnier M, Roch A, Forel JM, Thirion X, Arnal JM, Donati S, Papazian L. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit Care Med 2004;32:113–119. 4 Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, et al.; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107–1116. 5 Mure M, Martling CR, Lindahl SG. Dramatic effect on oxygenation in patients with severe acute lung insufficiency treated in the prone position. Crit Care Med 1997;25:1539–1544. 6 Sud S, Friedrich JO, Taccone P, Polli F, Adhikari NK, Latini R, Pesenti A, Guerin ´ C, Mancebo J, Curley MA, et al. Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis. Intensive Care Med 2010;36:585–599. 7 Guerin ´ C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, et al.; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368:2159–2168. 8 Herridge MS, Tansey CM, Matte´ A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, et al., Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 2011;364:1293–1304.

Acute Exacerbations of COPD and Asthma Jayshil J. Patel and Jonathan D. Truwit Acute exacerbations of chronic obstructive pulmonary disease (COPD) and asthma are common reasons for admission to the intensive care unit (ICU). Common considerations and recent updates for patients with frequent COPD or asthma exacerbations are highlighted below. Chronic Obstructive Pulmonary Disease

Systemic corticosteroids are the mainstay of therapy for patients admitted with an acute exacerbation of COPD, but the optimal duration of this therapy has been a topic of debate. A recent trial randomized 314 patients to receive 5 or 14 days of prednisone at a dose of 40 mg daily and demonstrated noninferiority of the 5-day arm with respect to reexacerbation. Patients randomized to 5 days of corticosteroids had a reduction in length of hospital stay, but steroid-related adverse events were not different between the two groups (1), suggesting that a short course of therapy is sufficient in most exacerbations of COPD. Prevention of exacerbations is a key endpoint to evaluate chronic therapy for COPD. The combination of pulmonary 1308

rehabilitation, smoking cessation, and optimization of medications improves mental health, improves quality of life, and decreases healthcare use largely by reducing exacerbations (2). Pulmonary rehabilitation consisting of breathing retraining, extremity conditioning, education, and psychological support is thus recommended for all patients with symptomatic COPD. Finally, surgical management may play a role in reducing symptoms, exacerbations, and hospitalizations from COPD. The NETT study enrolled 1,218 patients with severe emphysema for lung volume reduction surgery, which improved survival, exercise capacity, and quality of life, especially in patients with upper lobe–predominant disease and low exercise tolerance. Although this procedure should be considered in this subset of patients, it should also be noted that the 30-day mortality was increased in patients with an FEV1 less than 20% and either a diffusing capacity of the lung for carbon monoxide less than 20% or homogenous emphysema (3). COPD and Asthma

Although COPD and asthma are often considered different diseases, it is worth noting that patients may demonstrate characteristics of these two obstructive lung disease phenotypes. The COPD–asthma overlap phenotype is based on the major criteria of FEV1/FVC less than 70% with positive bronchodilator response. Patients tend to be younger with less smoking history than most patients with COPD. Given an increased severity and frequency of exacerbations, the early use of inhaled corticosteroids is recommended for this patient population (4). COPD and asthma exacerbations also present similar challenges when they require the administration of supportive positive pressure ventilation. Hypotension in a mechanically ventilated patient with COPD or asthma may be a consequence of auto-PEEP, recognized by continued expiratory flow on the flow– time waveform up to the initiation of the subsequent breath. Management includes increasing expiratory time to allow for complete exhalation, best achieved by reducing respiratory rate but occasionally requiring intermittent disconnection from the ventilator circuit (5). Asthma

Asthma exacerbation during pregnancy threatens the health of both the pregnant woman and the developing fetus. The goals and management of asthma management in pregnant women are similar to those of the nonpregnant patient, focused on symptoms and preventing exacerbations using a stepwise approach based on asthma control. Systemic corticosteroids are safe, and no adjustment is needed should an exacerbation occur. If labor is to be induced, carboprost should be avoided as it can trigger bronchospasm (6). Patient with certain subtypes of asthma may benefit from medications other than inhaled corticosteroids and bronchodilators, which are the mainstay of asthma therapy. Omalizumab is a recombinant human IgG1 that binds to circulating IgE. It may be considered as add-on therapy in patients with moderate to severe allergic asthma with serum IgE levels between 30 and 700, positive allergic skin testing to a perennial antigen, and incomplete control of asthma despite high-dose inhaled corticosteroids (7). Bronchial thermoplasty applies heat through bronchoscopy to reduce airway smooth muscle in asthma. AnnalsATS Volume 11 Number 8 | October 2014

ATS CORE CURRICULUM Due to the risks of the procedure and lack of long-term data, it should be performed in adults with severe asthma in the context of an institutional review board–approved registry or a clinical study (8) (Table 1).

References 1 Leuppi JD, Schuetz P, Bingisser R, Bodmer M, Briel M, Drescher T, Duerring U, Henzen C, Leibbrandt Y, Maier S, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA 2013;309:2223–2231. 2 Hill K, Vogiatzis I, Burtin C. The importance of components of pulmonary rehabilitation, other than exercise training, in COPD. Eur Respir Rev. 2013;22:405–413. 3 Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, Weinmann G, Wood DE; National Emphysema Treatment Trial Research Group. A randomized trial comparing lung volumereduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059–2073. 4 Hardin M, Silverman EK, Barr RG, Hansel NN, Schroeder JD, Make BJ, Crapo JD, Hersh CP; COPDGene Investigators. The clinical features of the overlap between COPD and asthma. Respir Res 2011;12:127. 5 Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43:343–373. 6 Schatz M, Dombrowski MP. Clinical practice. Asthma in pregnancy. N Engl J Med 2009;360:1862–1869. 7 Bousquet J, Wenzel S, Holgate S, Lumry W, Freeman P, Fox H. Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest 2004;125:1378. 8 Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, Fiss E, Olivenstein R, Thomson NC, Niven RM, et al.; AIR2 Trial Study Group. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med 2010;181:116–124.

Toxidromes Maryam Sheikh and Janice L. Zimmerman A toxidrome is a constellation of signs, symptoms, laboratory abnormalities, and electrocardiographic findings suggestive of specific toxins. Sympathomimetic Toxidrome

Manifestations of a sympathomimetic toxidrome include agitation, tachycardia, tachypnea, hypertension, hyperthermia, mydriasis, diaphoresis, and seizures. The usual associated toxins are pseudoephedrine, cocaine, amphetamines, methamphetamines, and emerging psychoactive substances such as bath salts and synthetic cannabinoids. These newer substances are not detected by urine toxicology assays. Bath salts usually contain synthetic derivatives of cathinone, which can be inhaled, snorted, or injected. Patients present with typical sympathomimetic manifestations in addition to paranoia, hallucinations, delusions of invincibility, and violent behavior. Common complications are hyperthermia, seizures, stroke, rhabdomyolysis, and renal failure. Despite a short half-life, symptoms may persist more than 24 hours. High doses of benzodiazepines may be needed to control behavior. Use of ATS Core Curriculum

haloperidol and risperidone has been reported for prolonged symptoms of psychosis. Synthetic cannabinoid products (“K2” and “Spice”) have variable compositions and are commonly smoked or ingested. Manifestations are typical of a sympathomimetic toxidrome but persist for many hours to several days. Complications include arrhythmias, stroke, myocardial infarction, seizures, rhabdomyolysis, and particularly renal failure. Benzodiazepines are the primary therapy. Additional treatment for these intoxications is supportive, including volume resuscitation and assessment for complications. Gastrointestinal decontamination is usually not warranted. Narcotic Toxidrome

Prescription narcotic abuse has surpassed abuse of illicit drugs in United States resulting in increased overdoses and deaths. Patients typically present with a toxidrome of depressed level of consciousness, respiratory depression, and miosis. Management includes supportive care and naloxone given not to achieve total wakefulness but to reverse life-threatening respiratory depression. Although the initial dose of naloxone is 0.4 to 2 mg, higher doses (10–20 mg) are usually needed to reverse the effects of synthetic narcotics and those with long duration of action. Because the half-life of naloxone is 45 to 70 minutes, a naloxone infusion is often needed for sustained reversal. Anticholinergic Toxidrome

Manifestations of an anticholinergic toxidrome include tachycardia, hyperthermia, agitation, delirium, coma, mydriasis, dry skin and mucous membranes, decreased bowel sounds, urinary retention, and rarely seizures. This toxidrome may occur with cyclic antidepressants, antipsychotics, and antihistamines. In addition to supportive care, sodium bicarbonate to achieve a blood pH goal of 7.45 to 7.55 is indicated for hemodynamic instability and cardiac toxicity. The major effect of this intervention may be sodium loading, which may overcome the antidepressant blockade of myocardial sodium/potassium. In refractory cases, hypertonic saline and lipid emulsion may be considered. Use of 20% lipid emulsion (administered as a bolus of 1.5 ml/ kg) in toxicology has been increasing when standard interventions fail. Successful reversal of hemodynamic effects has been reported with lipophilic cardiotoxic medications, including verapamil, b-blockers, haloperidol, cyclic antidepressants, antipsychotics, organophosphates, and cocaine. The exact mechanism of action is unknown but may include acting as a lipid “sink” to decrease free drug levels, enhancing fatty acid transport across the mitochondrial membrane, or inotropic activity. Cardiovascular Toxidrome

A cardiovascular toxidrome may result in bradycardia as a result of exposure to b-blockers (BBs), calcium channel blockers (CCBs), clonidine, or digoxin. Associated hypotension usually results from negative inotropic effects rather than bradycardia. Glucagon (initial dose, 2–5 mg intravenous) is considered the primary antidote for BB toxicity and acts as an inotropic agent. Glucagon may have beneficial effects in CCB toxicity, but the first agent to administer in these circumstances is intravenous calcium (10 ml of calcium chloride). Higher doses and/or continuous infusion of calcium may be necessary along with monitoring of ionized 1309

ATS CORE CURRICULUM calcium. Calcium may also be helpful in BB toxicity that does not respond to glucagon. Insulin combined with glucose to prevent hypoglycemia is often advocated as the next intervention for CCB toxicity unresponsive to calcium. Variable dosing of insulin has been reported, but a reasonable starting dose is 0.5 units/kg/h with titration based on clinical response. Atropine is usually ineffective, and response to catecholamines is variable. Lipid emulsion and mechanical cardiac support could be considered in refractory cases (Table 2).

References 1 Baumann BM, Patterson RA, Parone DA, Jones MK, Glaspey LJ, Thompson NM, Stauss MP, Haroz R. Use and efficacy of nebulized naloxone in patients with suspected opioid intoxication. Am J Emerg Med 2013;31:585–588. 2 Boyer EW. Management of opioid analgesic overdose. N Engl J Med 2012;367:146–155. 3 Castellanos D, Thornton G. Synthetic cannabinoid use: recognition and management. J Psychol Pract 2012;18:86–93. 4 Holstege CP, Borek HA. Toxidromes. Crit Care Clin 2012;28:479–498. 5 Jerry J, Collins G, Streem D. Synthetic legal intoxicating drugs: the emerging ‘incense’ and ‘bath salt’ phenomenon. Cleve Clin J Med 2012;79:258–264. 6 Lheureux PE, Zahir S, Gris M, Derrey AS, Penaloza A. Bench-tobedside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers. Crit Care 2006;10:212. 7 Nelson ME, Bryant SM, Aks SE. Emerging drugs of abuse. Emerg Med Clin North Am 2014;32:1–28.

Hemodynamic Monitoring Amit Diwakar and Gregory A. Schmidt Critically ill patients with compromised tissue perfusion undergo hemodynamic surveillance so that the intensivist may obtain and interpret an array of data with the aim of making prompt and effective interventions. Determining the adequacy of cardiac output (CO) and predicting fluid-responsiveness (FR) are the dominant questions in detecting and managing circulatory failure. The pulmonary artery catheter (PAC) has been widely used to assess CO, mixed venous oxygen saturation, and intrapulmonary and intracardiac pressures. Once considered the standard of care, its use has declined in the last decade due to lack of mortality benefit in critically ill patients (1) and even in congestive heart failure (2). As newer, less invasive technologies aim to supplant the PAC, it is worth revisiting the limitations of the PAC that are likely also to plague newer devices. First, obtaining accurate data is often complicated. Intracardiac pressures are subject to wide fluctuations in intrathoracic pressure with respiration; hence, obtaining end-expiratory data is essential for validity. Second, even accurate estimations of filling pressures or CO rarely allow judgments regarding whether these values are adequate for that patient at that time. Furthermore, even given accurate hemodynamic data, clinicians often fail to agree on therapy (3). Targeted resuscitation is attractive, but appropriate targets are not self-evident and achieving hemodynamic goals often involves tradeoffs that may cause harm. Static preload measures of the central venous and pulmonary artery occlusion pressures have been shown to be unhelpful in 1310

predicting FR (4). This limitation of static predictors has led to interest in dynamic indicators. High-volume positive-pressure ventilation produces pleural pressure changes that affect stroke volume in a cyclical fashion, largely by varying right atrial filling. Larger fluctuations in stroke volume, vascular flow, and vena caval diameter are seen in preload-dependent individuals. A 13% variation in pulse pressure with breathing is highly sensitive and specific for predicting FR (5), and useful cutoff values have been determined for respiratory-induced variations in vena caval diameter, aortic and brachial artery flow velocity, left ventricular outflow tract velocity–time integral, and cardiac volumes derived from bioimpedance and bioreactance. Prerequisites for validity of these methods are tidal volume of 8 to 12 ml/kg, a fully passive patient, regular cardiac rhythm, and the absence of acute cor pulmonale. Passive leg-raising returns blood held in the “capacitance” veins the heart and is a reliable indicator of FR irrespective of ventilation mode and cardiac rhythm (6). However, it is not reliable when there is severe intraabdominal hypertension. Bedside goal-directed echocardiography is now commonplace for the assessment of shock (7) as it is rapid and allows serial assessment. It uses four standard chest views to evaluate ventricular size and function and a subcostal view of the inferior vena cava. The subcostal view is helpful in assessing FR (8), but goal-directed echocardiography can also prove crucial in cases of unsuspected ventricular dysfunction, hypovolemia, pericardial tamponade, or acute valve failure. A variety of devices available in the ICU today provide hemodynamic data that need cautious interpretation. The intensivist needs to not only keep abreast of changing technology but also be aware of its limitations. Sorting out useable data from a sea of information is both challenging and critical to optimal outcomes (Table 3).

References 1 Harvey S, Harrison DA, Singer M, Ashcroft J, Jones CM, Elbourne D, Brampton W, Williams D, Young D, Rowan K; PAC-Man Study Collaboration. Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PACMan): a randomised controlled trial. Lancet 2005;366:472–477. 2 Binanay C, Califf RM, Hasselblad V, O’Connor CM, Shah MR, Sopko G, Stevenson LW, Francis GS, Leier CV, Miller LW; ESCAPE Investigators and ESCAPE Study Coordinators. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA 2005;294:1625–1633. 3 Jain M, Canham M, Upadhyay D, Corbridge T. Variability in interventions with pulmonary artery catheter data. Intensive Care Med 2003;29:2059–2062. 4 Osman D, Ridel C, Ray P, Monnet X, Anguel N, Richard C, Teboul JL. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med 2007;35:64–68. 5 Michard F, Boussat S, Chemla D, Anguel N, Mercat A, Lecarpentier Y, Richard C, Pinsky MR, Teboul JL. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med 2000;162:134–138. 6 Cavallaro F, Sandroni C, Marano C, La Torre G, Mannocci A, De Waure C, Bello G, Maviglia R, Antonelli M. Diagnostic accuracy of passive leg raising for prediction of fluid responsiveness in adults: systematic review and meta-analysis of clinical studies. Intensive Care Med 2010;36:1475–1483.

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ATS CORE CURRICULUM 7 Schmidt GA, Koenig S, Mayo PH. Shock: ultrasound to guide diagnosis and therapy. Chest 2012;142:1042–1048. 8 Barbier C, Loubieres Y, Schmit C, Hayon J, Ricome JL, Jardin F, Vieillard-Baron A. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med 2004;30:1740–1746.

Cardiac Critical Care 1: Hypertensive Crisis, Arrhythmias, and Acute Coronary Syndromes

Regular

Narrow Complex (QRS < 120)

Wide Complex (QRS > 120)

Gregory T. Means and Jason N. Katz Hypertensive Crises

Hypertensive crises are differentiated into emergencies or urgencies based on the presence or absence of end-organ injury, respectively (1). These common conditions are more common among African American men and associated with poorly controlled chronic hypertension and poor medication adherence (2). Hypertensive crises are associated with high readmission and mortality rates (3). Hypertensive emergency requires the administration of parenteral antihypertensive therapies in a critical care setting with careful monitoring. Although limited data exist, consensus guidelines recommend reducing the mean arterial pressure by no more than 25% (4). If blood pressure reduction is too rapid, tissue hypoperfusion and organ ischemia can occur in longstanding hypertensive patients who have chronically altered autoregulation (5). Hypertensive urgency may be effectively treated with oral medications and blood pressure reduction over days to weeks. Arrhythmias

Cardiac rhythm abnormalities commonly complicate the care of a critically ill patient. Atrial and ventricular ectopy, often seen during telemetry monitoring, are often not clinically important. Premature ventricular contractions are generally benign, but increasing frequency may herald a malignant arrhythmia or suggest the presence of electrolyte abnormalities, acid–base disturbances, or cardiac ischemia. Accurate identification of abnormal rhythms begins by characterizing the regularity and width of QRS complex (Figure 1). Atrial fibrillation and atrial flutter are commonly encountered in the critical care setting and are treated primarily with rate control and anticoagulation for stroke prevention. Adenosine transiently blocks conduction through the atrioventricular (AV) node and can be both diagnostic and therapeutic. Arrhythmias dependent on AV node conduction (AV reentrant tachycardia and AV nodal reentrant tachycardia) may terminate with adenosine. Adenosine and other nodal-blocking agents should be avoided if there is concern for Wolff-Parkinson-White (WPW) syndrome. Hemodynamic instability from any arrhythmia should prompt immediate initiation of advanced cardiac life support with consideration for cardioversion or defibrillation. Similarly, bradyarrhythmias that are symptomatic or unstable merit temporary or permanent pacing. Acute Coronary Syndrome

Acute coronary syndrome (ACS) represents a spectrum of cardiac ischemia from unstable angina, to non–ST-segment elevation myocardial infarction (NSTEMI), to ST-segment elevation MI (STEMI). Greater than 90% of ACS events result from the disruption of a vulnerable and unstable atherosclerotic ATS Core Curriculum

Irregular

Sinus tachycardia Atrial tachycardia Atrial flutter AVNRT AVRT Junctional tachycardia

Atrial fibrillation Multifocal atrial tachyacardia Frequent PACs

SVT with aberrancy SVT with pre-excitation Ventricular tachycardia Antidromic tachycardia Hyperkalemia

Atrial fibrillation with aberrancy Atrial fibrillation with preexcitation Polymorphic ventricular tachycardia

Figure 1. Approach to tachyarrhythmias. A systematic approach that characterizes arrhythmias as having a wide or narrow QRS complex and as being regular or irregular is helpful in identifying the specific irregular rhythm. AVNRT = atrioventricular nodal reentrant tachycardia; AVRT = atrioventricular reentrant tachycardia; PACs = premature atrial contraction; SVT = supraventricular tachycardia.

plaque, with subsequent platelet aggregation and thrombus formation. Critically ill patients with myocardial oxygen supply decreased and demand increased may also suffer from ACS. STEMI is an electrocardiographic diagnosis (.1 mm of ST-segment elevation in two anatomically contiguous limb leads, .2 mm in contiguous precordial leads, or a new left bundle branch block). NSTEMI or unstable angina may not manifest on the electrocardiogram but are suggested by symptoms and, in the case of NSTEMI, an elevation in cardiac biomarkers. All individuals presenting with an ACS should receive a full-dose aspirin, b-blocker (unless hemodynamically unstable), systemic anticoagulation, and consideration for antiplatelet therapy (6, 7). An early invasive strategy involving cardiac catheterization is recommended for most patients with ACS (6), and immediate reperfusion therapy should be performed for those with STEMI (7) (Table 3).

References 1 Cherney D, Straus S. Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature. J Gen Intern Med 2002;17:937–945. 2 Shea S, Misra D, Ehrlich MH, Field L, Francis CK. Predisposing factors for severe, uncontrolled hypertension in an inner-city minority population. N Engl J Med 1992;327:776–781. 3 Katz JN, Gore JM, Amin A, Anderson FA, Dasta JF, Ferguson JJ, Kleinschmidt K, Mayer SA, Multz AS, Peacock WF, et al.;STAT Investigators. Practice patterns, outcomes, and end-organ dysfunction for patients with acute severe hypertension: the STAT registry. Am Heart J 2009;158:599–606. 4 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, et al.; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560–2572. 5 Grossman E, Masserli FH, Grodzicki T, et al. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA 1996;276:3128–3131. 6 Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, Fesmire FM, Ganiats TG, Lincoff AM, et al. 2012 ACCF/ AHA focused update of the guideline for the management of patients

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ATS CORE CURRICULUM with unstable angina/non-ST-elevation myocardial infarction. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2012; 60:645–681. 7 O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, et al.; American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. A Report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78–e3140.

Cardiac Critical Care 2: Decompensated Heart Failure, Cardiogenic Shock, and Mechanical Circulatory Support Akshay S. Desai The vast majority of symptoms in patients with worsening heart failure are related to worsening congestion (1). Pharmacologic therapy of patients with acute decompensated heart failure is accordingly targeted at relief of congestion through optimization of normal hemodynamics and volume status. Selection of appropriate treatment is guided by bedside assessment of filling pressures (“wet” vs. “dry”) and end-organ perfusion (“warm” vs. “cold”) to subclassify patients into one of four hemodynamic profiles (2, 3) (Figure 2). Elevated filling pressures are suggested by symptoms of orthopnea and typical physical examination findings of congestion, including elevated jugular venous pressure, S3 gallop, peripheral edema, ascites, and, less commonly, rales. Narrow pulse pressure, cool extremities, altered mental status, and worsening renal function may indicate reduced stroke volume/ cardiac output and end-organ hypoperfusion. Although not appropriate for routine use in heart failure management, invasive hemodynamic data from the pulmonary artery catheter may help to refine this classification by directly quantifying right and left heart filling pressures and cardiac output (4). The vast majority of patients with acute decompensated heart failure present in hemodynamic profile B (“warm and wet”),

indicating adequate perfusion but high filling pressures. For these patients, the primary goal of treatment is aggressive decongestion through administration of intravenous diuretics. Data from prospective, randomized, controlled trials suggest that this may be accomplished equivalently through use of bolus dosing or continuous infusion of loop diuretics and augmented by combination treatment with thiazide diuretics (5). After restoration of normal hemodynamics (profile A), a maintenance heart failure regimen can be initiated by titration of diseasemodifying treatments (b-blockers, angiotensin-converting enzyme inhibitors, mineralocorticoid receptor antagonists) to facilitate favorable ventricular remodeling and slow disease progression over the long term. Patients with acute decompensated heart failure who are “cold and wet” (profile C) represent a challenging group in whom effective decongestion is complicated by low cardiac output and renal hypoperfusion. In these patients, administration of intravenous vasodilator or inotropic drugs may help to recruit contractile reserve and enhance forward cardiac output. Intravenous vasodilators, such as sodium nitroprusside, nesiritide, and nitroglycerine, are typically preferred over inotropes due to lower risk of proarrhythmic side effects and mortality (6); however, these agents may be poorly tolerated in patients with normal or low systemic vascular resistance in whom excessive vasodilation may simply provoke worsening hypotension. If hemodynamics are uncertain or difficult to ascertain at the bedside, selection of appropriate therapy for profile C patients may be guided by invasive hemodynamic assessment with a pulmonary artery catheter. Selected patients with profile C present with evidence of marked and prolonged hypotension that reflects severely depressed cardiac output and cardiogenic shock. Such patients are at extremely high risk for mortality and require early consideration of mechanical circulatory support with intraaortic balloon counterpulsation, percutaneous ventricular assist devices, or (in the case of cardiopulmonary failure) extracorporeal membrane oxygenation for hemodynamic stabilization (7). For those in whom shock is a consequence of acute myocardial infarction, early reperfusion of the infarct-related artery is the only strategy proven to reduce mortality (8) (Table 3).

Hemodynamic Subsets of ADHF

References

Filling Pressures

No

Yes

High (elevated PCWP)

No

Yes

A PCWP normal CI normal

B PCWP elevated CI normal

Warm and Dry Inadequate (CI Reduced)

Perfusion

4C/FPO

Adequate (CI Preserved)

Low (Normal PCWP)

D PCWP low/normal CI decreased Cold and Dry

Warm and Wet C PCWP elevated CI decreased Cold and Wet

Figure 2. Hemodynamic subsets of acute decompensated heart failure. CI = cardiac index; PCWP = pulmonary capillary wedge pressure. Based on concepts presented in References 2 and 3.

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1 Zile MR, Bennett TD, St John Sutton M, Cho YK, Adamson PB, Aaron MF, Aranda JM Jr, Abraham WT, Smart FW, Stevenson LW, et al. Transition from chronic compensated to acute decompensated heart failure: pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation 2008;118:1433– 1441. 2 Stevenson LW. Tailored therapy to hemodynamic goals for advanced heart failure. Eur J Heart Fail 1999;1:251–257. 3 Nohria A, Lewis E, Stevenson LW. Medical management of advanced heart failure. JAMA 2002;287:628–640. 4 Binanay C, Califf RM, Hasselblad V, O’Connor CM, Shah MR, Sopko G, Stevenson LW, Francis GS, Leier CV, Miller LW; ESCAPE Investigators and ESCAPE Study Coordinators. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA 2005;294: 1625–1633. 5 Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, et al.; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in

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ATS CORE CURRICULUM patients with acute decompensated heart failure. N Engl J Med 2011;364:797–805. 6 Kalogeropoulos AP, Marti CN, Georgiopoulou VV, Butler J. Inotrope use and outcomes among patients hospitalized for heart failure: impact of systolic blood pressure, cardiac index, and etiology. J Card Fail 2014; 20:593–601. 7 Werdan K, Gielen S, Ebelt H, Hochman JS. Mechanical circulatory support in cardiogenic shock. Eur Heart J 2014;35:156–167. 8 Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD, Buller CE, Jacobs AK, Slater JN, Col J, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med 1999;341: 625–634.

Mechanical Ventilation Neil R. MacIntyre Positive pressure mechanical ventilation (PPMV) has been providing respiratory life support for almost a century. Over time, devices have become increasingly sophisticated and outcomes have improved, largely because ICU clinicians have come to realize that inappropriate management strategies can result in considerable harm. Despite these advances, challenges remain; three of the more important of these—providing lung protection, optimizing patient– ventilator interactions, and promptly removing PPMV when no longer needed—are discussed below. Throughout these discussions, it is important to remember that PPMV is never a therapeutic tool. Rather, PPMV will always remain a support device, capable only of “buying time” while having a significant potential for harm. Providing Lung Protection

The lung can be injured in several ways by PPMV: ventilatorinduced lung injury (VILI) mechanisms include: (1) Excessive stretch at end inspiration, generally associated with transpulmonary end-inspiratory distending pressures exceeding 30 cm H2O; (2) Repetitive cycling of the lung with higher-thannormal tidal volumes; (3) Repetitive collapse-reopening of alveolar units during exhalation and subsequent inhalation. Frequency of stretch, acceleration/velocity of stretch, excessive O2 exposure, and vascular pressures may also contribute to VILI. PPMV settings must focus on limiting both end-inspiratory and tidal stretch along with minimizing alveolar collapsereopening. In practice, this means the “default” tidal volume should be initiated at 6 ml/kg (ideal body weight) and subsequent titrations made to maintain the end-inspiratory lung distending pressure (Pplat corrected for any chest wall effects) at less than 30 cm H2O. Although imaging or mechanical assessments would seem helpful in setting PEEP, neither is currently practical for general use. More commonly, PEEP-F IO2 tables are used to balance PO2 goals versus Pplat effects versus FIO2 needs. In general, more severe lung injury benefits from aggressive PEEP use and less severe injury benefits from less aggressive PEEP use. When lung protection cannot be provided with conventional settings, other options include airway pressure release ventilation, high-frequency ventilation, and extracorporeal support. Although each has theoretical appeal, outcome studies are either nonexistent or conflicting. ATS Core Curriculum

Noninvasive ventilation could theoretically enhance lung protection by avoiding intubation. This benefit, however, has only been clearly demonstrated in acute exacerbations of COPD and cardiogenic pulmonary edema. Improving Patient–Ventilator Synchrony

Synchronous patient–ventilator interactions mean that the ventilator is sensitive/responsive to the initiation, modulation, and termination of a patient’s ventilatory effort. Dyssynchronous interactions lead to patient discomfort, unnecessary sedation, prolonged duration of mechanical ventilation, and even increased morbidity/mortality. Minimizing dyssynchrony with conventional modes requires careful assessment of the triggering process, the flow delivery pattern, and the breath-cycling process. Triggers should be set as sensitive as possible, and small amounts of PEEP can be used to lessen the imposed triggering load from air trapping. Flow settings should be matched to patient effort, and pressure-targeted breaths with variable flow may be particularly useful. Breath-cycling criteria should be set to match the patient’s inspiratory demand. Novel approaches to improving synchrony include proportional assist ventilation and neurally adjusted ventilatory assist. Both have theoretical appeal, but neither has documented outcome benefits as yet. Providing Prompt Discontinuation of Support

Delays in ventilator discontinuation result in increased length of stay, higher costs, longer exposure to distending pressures, and infection risks. Attempts to increase withdrawal aggressiveness, however, must be balanced against the risk of premature withdrawal with consequent airway loss, aspiration, and inspiratory muscle fatigue. An evidence-based task force has recommended a daily assessment process for most patients requiring PPMV to determine suitability for a spontaneous breathing trial (SBT). In patients passing the SBT, separate assessments are required to determine if the artificial airway can be removed. Extubation failures can be expected in 10 to 15% of all extubations. However, in some patients, especially patients with COPD, an extubation failure caused by increasing inspiratory muscle overload might be managed by noninvasive ventilation. Attempts have been made to “automate” the weaning process with feedback algorithms designed to progressively reduce pressure support. However, to date, none have been shown to reduce ventilator days when compared with clinical protocols using daily SBTs. One role for these automated strategies might be to serve as a marker of recovery in patients receiving prolonged support with multiple failed SBTs (Table 1). n Author disclosures are available with the text of this article at www.atsjournals.org.

References 1 Chiumello D, Carlesso E, Cadringher P, Caironi P, Valenza F, Polli F, Tallarini F, Cozzi P, Cressoni M, Colombo A, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med 2008;178:346– 355.

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ATS CORE CURRICULUM 2 Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, Patroniti N, Cornejo R, Bugedo G. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 2006;354:1775–1786. 3 Gilstrap D, MacIntyre NR. Patient-ventilator interactions: implications for clinical management. Am J Respir Crit Care Med 2013;188:1058– 1068. 4 Tremblay LN, Slutsky AS. Ventilator-induced lung injury: from the bench to the bedside. Intensive Care Med 2006;32:24–33. 5 NIH ARDS Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301–1308.

6 Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and metaanalysis. JAMA 2010;303:865–873. 7 ACCP/AARC/SCCM Task Force. Evidence-based guidelines for weaning and discontinuing mechanical ventilatory support. Chest 2001;120:375S–395S. 8 Ferguson ND, Esteban A; Ventila Group. Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation. Am J Respir Crit Care Med 2011;184: 430–437.

Table 1. Key updates: respiratory failure and management Acute respiratory distress syndrome (ARDS) The 2012 Berlin Definition refined the definition of ARDS to include disease severity categories, require a minimum level of PEEP, exclude patients with respiratory failure .1 wk from symptoms onset, remove pulmonary capillary wedge pressure criteria, remove requirement for mechanical ventilation. Primary objective of care is to use a lung-protective ventilator strategy targeting low tidal volumes (6 ml/kg predicted body weight) and minimizing plateau pressures (,30 cm H2O). Recent trails have suggested that early neuromuscular blockade and prone positioning provide a mortality benefit in selected patients with ARDS. Survivors of ARDS frequently suffer from prolonged physical, cognitive, and psychological morbidity. Obstructive lung diseases A short course of corticosteroids (5 d) is noninferior to a longer course (14 d) for an acute exacerbation of COPD. Mechanical ventilation of patients with asthma and COPD exacerbations should be monitored for auto-PEEP, which may cause hypotension. Patients admitted for exacerbations should be evaluated to optimize chronic therapies that decrease symptoms and prevent future exacerbations. Mechanical ventilation Noninvasive ventilation is used in many settings to provide ventilatory support without the morbidity of intubation and has been clearly demonstrated to provide benefit in acute exacerbations of COPD and cardiogenic pulmonary edema. Ventilator strategies that minimize alveolar collapse and reopening while limiting end-expiratory stretch will minimize ventilator-induced lung injury. Effort should be paid to optimize patient–ventilator synchrony to reduce patient discomfort, reduce sedative and analgesic requirements, and potentially reduce the length of mechanical ventilation. Patients should be assessed daily to determine if they are candidates for discontinuation of potentially harmful mechanical ventilation. Definition of abbreviations: COPD = chronic obstructive pulmonary disease; PEEP = positive end-expiratory pressure.

Table 2. Key updates: toxidromes Sympathomimetic toxidrome The sympathomimetic toxidrome, caused by pseudoephedrine, cocaine, amphetamines, bath salts, and synthetic cannabinoids, is characterized by agitation, tachycardia, tachypnea, hypertension, hyperthermia, mydriasis, diaphoresis, and seizures. The primary therapy includes benzodiazepines and supportive care. Narcotic toxidrome Prescription narcotic abuse has surpassed illicit drug abuse as the leading cause of opioid overdose. Naloxone, often in high doses or administered as an infusion, is necessary for effective treatment. Anticholinergic toxidrome The anticholinergic toxidrome, caused by cyclic antidepressants, antipsychotics, and antihistamines, is characterized by tachycardia, hyperthermia, agitation, delirium, mydriasis, dry skin, and urinary retention. The therapy includes supportive care and sodium bicarbonate for cardiac toxicity. Lipid emulsions have also been used for severe cases. Cardiovascular toxidrome b-Blockers, calcium channel blockers, clonidine, and digoxin can cause bradycardia, negative inotropy, and hemodynamic collapse. b-Blocker toxicity is treated first with glucagon. Calcium channel blocker toxicity is treated first with intravenous calcium.

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ATS CORE CURRICULUM Table 3. Key updates: cardiovascular critical care Monitoring Hemodynamic monitoring may help clinicians guide supportive care of patient suffering from inadequate tissue perfusion by determining fluid responsiveness and the adequacy of the cardiac output. The usefulness of hemodynamic monitoring may be limited by the accuracy of measure, the limits of even accurate measures in determining if a patient’s needs are being met, and lack of consensus as to how to use the data collected. Dynamic indicators, when they can be properly measured, have proven to be helpful predictors of fluid responsiveness. Cardiovascular disease states Hypertensive emergency, characterized by hypertension with evidence of end-organ injury, should be treated with a prompt but controlled and modest (,25%) reduction in blood pressure. Unstable angina and NSTEMI are characterized by symptoms and possibly by electrocardiogram and elevated biomarkers (with NSTEMI) and should be treated with aspirin, b-blocker, anticoagulation. Antiplatelet agents and early coronary angiography should be strongly considered. ST-segment elevation is suggested by symptoms and confirmed with electrocardiogram. Treatment is early reperfusion therapy. Congestive heart failure subtype can be specified and therapy guided by classifying the patient’s filling pressures (“wet” or “dry”) and end-organ perfusion (“warm” or “cold”). Definition of abbreviation: NSTEMI = non–ST-segment elevation myocardial infarction.

ATS Core Curriculum

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