When Better Is the Enemy of Good: The Optimal Heart Rate During Therapeutic Cooling* Kees H. Polderm an, M D , PhD
Department of Critical Care Medicine University of Pittsburgh Medical Center Pittsburgh, PA Joseph Varon, M D , FACP, FCCP, FC C M , F R S M
Department of Acute and Continuing Care The University of Texas Health Science Center at Houston Houston, TX; Department of Medicine The University of Texas Medical Branch at Galveston Galveston, TX; and Department of Critical Care Services University General Hospital Houston, TX
ne of the most fundamental rules in medicine is “Primum Non Nocere”—to first, do no harm. However, unfortunately, sometimes our quest to “improve” physiologic variables in our patients can lead to harm; this is when “better” becomes the enemy of good. Recent examples of such unintended consequences include use of intensive insulin therapy to induce strict normoglycemia in critically ill patients, linked to increased risk of death (1, 2); the use of starches to improve hemodynamics and increase efficacy of resuscitation in patients with severe sepsis, linked to increased risk of renal failure and death (2, 3); excessive oxygenation in patients with out-of-hospital cardiac arrest (OHCA), linked to higher mor tality (4); aggressive treatment of intracranial arterial steno sis with elective stent placement in addition to drug therapy, linked to increased risk of stroke and higher mortality (5); use of long-acting (3-blockers to reduce cardiac risk in the peri operative setting, linked to increased risk of stroke and higher mortality (6); and quite possibly use of long-acting antihy pertensives in the acute phase of neurological injury, linked to increased mortality when “overshoot” (accidental hypoten sion) occurs (7). This list could easily be expanded. A recurrent theme in many of these interventions is an overzealous attempt to restore (perceived) physiological or ref erence values. Often it is the “overshoot” of efforts to restore “normal” values that is harmful, where the intervention itself may be neutral or even beneficial; but sometimes the concept
O
'See also p. 2401. Key Words: bradycardia; cardiac arrest; hypothermia; myocardial function; resuscitation The authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0000000000000600 2452
w w w .c c m jo u r n a l.o r g
of “normal” may change under pathophysiologic conditions, and trying to achieve “normal” values may itself be harmful. We should always keep in mind that for any given interven tion, risks may outweigh benefits and that our efforts to restore numbers to normal or supranormal could backfire. These observations come to mind when reading the article by Staer-Jensen et al (8) published in this issue of Critical Care Medicine. The authors, who work in a large tertiary referral cen ter for patients with OHCA, performed a retrospective cohort study in 111 of their patients to determine whether there was a link between bradycardia developing during therapeutic hypothermia (TH) and neurological outcome. The result may come as a surprise to some; the authors found that bradycardia during TH was associated with favorable neurologic outcome at hospital discharge. They conclude that bradycardia during TH should not be aggressively treated in most patients (8). The authors also established a dose-response relationship between bradycardia and favorable outcome, that is, the lower the heart rate, the greater the likelihood of favorable outcome. Although the study is limited by its retrospective design, finding such a dose-response relationship makes it more plausible that the observed link is genuine. These findings suggest that in many cases our desire for the heart rate to be “normal” under hypothermic conditions may be misguided and that attempts to “fix” the heart rate may be yet another example of better being the enemy of good. To better understand the results of this study, it is useful to take a brief look at the physiological links between temperature and heart rate. Hypothermia has multiple direct and indirect effects on heart rhythm and myocardial function. A mild drop in temperature to levels just below normal (±36.0°C) initially leads to an increase in plasma levels of norepinephrine and activation of the sympathetic nerve system. This induces con striction of peripheral vessels (particularly in the skin) and a shift of blood from peripheral (small) veins to deeper veins in the core compartment of the body, leading to an increase in venous return to the heart (9). This hypothermia-induced rise in venous return initially leads to mild sinus tachycardia and is one of the factors contributing to so-called cold diuresis (the others being a decrease in antidiuretic hormone [ADH] and renal ADH receptor levels, tubular dysfunction, and activa tion of atrial natriuretic peptide) (9). Cold diuresis can lead to hypovolemia, which can sustain and increase tachycardia (9). The initial increase in heart rate is reversed as core tem perature decreases further, below 35.5°C. Heart rate begins to drop progressively as core temperature decreases, and soon sinus bradycardia ensues; at 32°C, the normal heart rate will be 35-45 beats/min (although there is wide interpatient variabil ity). This is caused by a hypothermia-induced decrease in the rate of spontaneous depolarization of cardiac pacemaker cells, including those of the sinus node, combined with decreased November 2014 • Volume 42 • Number 11
Editorials
speed of myocardial impulse conduction and increased dura tion of action potentials (9). These changes are reflected in the patients’ electrocardiogram and may include prolonged PR intervals, increased QT interval, and widening QRS complex. Less frequently, so-called Osborne waves may develop (9,10). Some regard such changes as pathological and potentially harmful. Large studies assessing the efficacy of TH for vari ous types of neurologic injury have reported bradycardia as a side effect or arrhythmia (11); many hypothermia protocols and published reviews list “bradyarrhythmias” as an exclu sion criterion and recommend rewarming, chronotropic sup port, or pacemaker insertion if bradycardia develops (12-14). Others have argued in this journal and elsewhere that such changes are essentially physiologic adaptations, should not be regarded as pathological arrhythmia’s, and usually do not require treatment (9, 10, 15). The argument has pertained to mild-to-moderate hypothermia, that is, temperatures between 30°C and 35°C; it is well recognized that deep hypothermia, that is, temperature less than or equal to 28°C, does increase the risk of life-threatening arrhythmias (beginning with atrial fibrillation, followed by shock-resistant ventricular fibrillation, shock resistant in that deeply hypothermic myocardial tissue becomes more difficult to defibrillate, and less responsive to antiarrhythmic drugs) (9). However, there is compelling evidence that moderate hypo thermia has no such effect and that in fact the opposite is true: mild-to-moderate hypothermia decreases the risk of arrhyth mias and makes the myocardium less resistant to electric defi brillation. Boddicker et al (16) and Rhee et al (17) studied the effect of temperature on the likelihood of successful defibrilla tion in pigs. Both reported higher rates of return of spontane ous circulation, greater likelihood of successful defibrillation with fewer shocks required, and lower risk of postdefibrilla tion asystole under hypothermic conditions (15, 16). Even at 30°C, the results were better than at 37°C. Harada et al (18) reported similar findings in a rabbit model. Several case studies have reported successful use of TH to treat junctional ectopic tachycardia in children (19-21). Taken together, these find ings suggest that moderate hypothermia decreases the risk of arrhythmias and may facilitate their treatment if they do occur. Further, TH increases myocardial contractility in most patients (though mild diastolic dysfunction may occur), and blood pressure remains stable or increases unless the patient is hypovolemic (9, 10); but when hypothermia-induced bra dycardia is “treated” (i.e., heart rate is artificially increased to “normal” values), this leads to decreased myocardial contrac tility, worsening myocardial function, and increased myocar dial oxygen demand (22,23). These physiological observations and experimental data dovetail nicely with the results reported by Staer-Jensen et al (8). To be sure, their study has important limitations. Its ret rospective design makes it difficult to draw firm conclusions. The presence of tachycardia in patients during TH (including a “normal” heart rate, which should be regarded as tachycardia when a patient is hypothermic) may reflect more severe myo cardial injury or the presence of additional pathology such as Critical Care Medicine
preexisting infection or other disease. Absence of bradycardia may very well be a marker, rather than the cause of favorable outcome. Supporting this view is that on multivariate analysis, the authors found that bradycardia 8 hours postischemia was not significantly associated with better neurologic outcome when adjusting for all covariates (8). The question whether bradycardia actually improves out come can only be answered with a prospective randomized trial. Nevertheless, there are many theoretical considerations and experimental data suggesting that bradycardia might be favorable, and we should probably resist any urge to “fix” the low heart rate in most patients. Certainly, TH treatment should not be withheld because of the presence/risk of arrhythmias or bradycardia. Perhaps our mindset needs to change; rather than reflexively trying to “fix” temperature-appropriate low heart rates, maybe we should question why a given patient does not develop temperature-appropriate bradycardia. Perhaps there is shivering/discomfort? Maybe hypovolemia is present, due to cold diuresis and/or the postcardiac arrest syndrome that many cardiac arrest (CA) patients develop (24, 25)? Perhaps the apparent sinus rhythm is actually an underlying atrial flut ter? Maybe an infection is developing, due to aspiration before the airway was secured? Of note, while bradycardia appears to be an adaptive or even protective response, this very likely does not apply to hypo tension. Cerebral oxygenation depends mainly on perfusion pressure rather than cardiac output; especially when cerebral autoregulation is impaired (as is often the case after OHCA) (26), the brain is highly perfusion dependent. A recent study published in Critical Care Medicine found that average mean arterial pres sure (MAP) greater than or equal to 70 mm Hg in patients with OHCA was associated with better neurological outcome (27). All this suggests that we should look very carefully at our interventions and desired variables in patients with OHCA, particularly while undergoing TH. We should realize that bradycardia is the normal situation under hypothermic con ditions and that if something is not broken, we should prob ably not attempt to fix it. Patients with bradycardia who have a good MAP, urine production, and lactate clearance and accept able venous/mixed venous saturation likely do not require interventions. In general, we should strive to keep things as close to normal (for that individual patient) as possible, but the “normal” should be temperature adjusted. Bradycardia is normal, hypotension is not; hypo- and hypercapnia as well as hypoxia and hyperoxia should be avoided (4, 28), with blood gases being corrected for temperature (9,10). Future, prospective clinical trials should address what the optimal physiologic variables in post-CA patients should be. Apart from MAP, heart rate, and ventilation, these should include the optimal temperature and duration of therapeutic cooling. The current study provides guidance on how to manage our patients pending such trials, and again it reminds us that with appropriate management, the rate of survival with good neurologic outcome after witnessed ventricular tachycardia/ ventricular fibrillation arrest can and should be 50% or higher. w w w .c c m jo u r n a l.o r g
2453
Editorials
REFERENCES 1. Finfer S, Liu B, Chittock DR, et al; NICE-SUGAR Study Investigators: Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012;367:1108-1118 2. Brunkhorst FM, Engel C, Bloos F, et al; German Competence Network Sepsis (SepNet): Intensive insulin therapy and pentastarch resuscita tion in severe sepsis. N Engl J Med 2008; 358:125-139 3. PernerA,HaaseN,Guttormsen AB,etal;6STrialGroup;Scandinavian Critical Care Trials Group: Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012; 367:124-134 4. Kilgannon JH, Jones AE, Shapiro Nl, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators: Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA 2010; 303:2165-2171 5. Chimowitz Ml, Lynn MJ, Derdeyn CP, et al; SAMMPRIS Trial Investigators: Stenting versus aggressive medical therapy for intra cranial arterial stenosis. N Engl J Med 2011; 365:993-1003 6. Devereaux PJ, Yang H, Yusuf S, et al; POISE Study Group: Effects of extended-release metoprolol succinate in patients undergoing non cardiac surgery (POISE trial): A randomised controlled trial. Lancet 2008;371:1839-1847 7. Mayer SA, Kurtz P, Wyman A, et al; STAT Investigators: Clinical prac tices, complications, and mortality in neurological patients with acute severe hypertension: The Studying the Treatment of Acute hyperTension registry. Crlt Care Med 2011; 39:2330-2336 8. Strer-Jensen H, Sunde K, Olasveengen TM, et al: Bradycardia During Therapeutic Hypothermia Is Associated With Good Neurologic Outcome in Comatose Survivors of Out-of-Hospital Cardiac Arrest. Crit Care Med 2014; 42:2401 -2 4 0 8 9. Polderman KH: Therapeutic temperature management: State of the art in the critically ill: Mechanisms of action, physiologic effects and complications of hypothermia. Crlt Care Med 2009; 37:S186-S202 10. Polderman KH, Herold I: Therapeutic hypothermia and controlled normothermia in the intensive care unit: Practical considerations, side effects, and cooling methods. Crit Care Med 2009; 37:1101-1120 11. Clifton GL, Miller ER, Choi SC, et al: Lack of effect of induc tion of hypothermia after acute brain injury. N Engl J Med 2001; 344:556-563 12. Deckard ME: Therapeutic hypothermia after cardiac arrest: What, why, who, and how. Am Nurs Today 2011; 6:23-29 13. Oommen SS, Menon V: Hypothermia after cardiac arrest: Beneficial, but slow to be adopted. Cleve Clin J Med 2011; 78:441 -4 4 8 14. Lakshmanan R, Sadaka F, Palagiri A: Therapeutic hypothermia: Adverse events, recognition, prevention and treatment strategies. In'. Therapeutic Hypothermia in Brain Injury. Sadaka F (Ed). InTech 2013. Available at: http://www.intechopen.com/books/therapeutichypothermia-in-brain-injury/therapeutic-hypothermia-adverse-events-
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recognition-prevention-and-treatment-strategies. Accessed August 14, 2014 15. Varon J, Marik PE, Einav S: Therapeutic hypothermia: A state-ofthe-art emergency medicine perspective. Am J Emerg Med 2012; 30:800-810 16. Boddicker KA, Zhang Y, Zimmerman MB, et al: Hypothermia improves defibrillation success and resuscitation outcomes from ventricular fibrillation. Circulation 2005; 111:3195-3201 17. Rhee BJ, Zhang Y, Boddicker KA, et al: Effect of hypothermia on transthoracic defibrillation in a swine model. Resuscitation 2005; 65:79-85 18. Harada M, Honjo H, Yamazaki M, et al: Moderate hypothermia increases the chance of spiral wave collision in favor of self-termi nation of ventricular tachycardia/fibrillation. Am J Physiol Heart Cire Physiol 2008; 294:H1896-H1905 19. Bash SE, Shah JJ, Albers WH, et al: Hypothermia for the treatment of postsurgical greatly accelerated junctional ectopic tachycardia. J Am Coll Cardiol 1987; 10:1095-1099 20. Balaji S, Sullivan I, Deanfield J, et al: Moderate hypothermia in the management of resistant automatic tachycardias in children. Br Heart J 1991; 66:221-224 21. Pfammatter JP, Paul T, Ziemer G, et al: Successful management of junctional tachycardia by hypothermia after cardiac operations in infants. Ann Thorac Surg 1995; 60:556-560 22. Lewis ME, Al-Khalidi AH, Townend JN, et al: The effects of hypother mia on human left ventricular contractile function during cardiac sur gery. J Am Coll Cardiol 2002; 39:102-108 23. Mattheussen M, Mubagwa K, Van Aken H, et al: Interaction of heart rate and hypothermia on global myocardial contraction of the isolated rabbit heart. Anesth Analg 1996; 82:975-981 24. Oksanen T, Skrifvars M, Wilkman E, et al: Postresuscitation haemo dynamics during therapeutic hypothermia after out-of-hospital cardiac arrest with ventricular fibrillation: A retrospective study. Resuscitation 2014; 85:1018-1024 25. Polderman KH, Varon J: Cool hemodynamics-The intricate interplay between therapeutic hypothermia and the post-cardiac arrest syn drome. Resuscitation 2014; 85:975-976 26. Sundgreen C, Larsen FS, Herzog TM, et al: Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest. Stroke 2001; 32:128-132 27. Kilgannon JH, Roberts BW, Jones AE, et al: Arterial blood pressure and neurological outcome after resuscitation from cardiac arrest. Crit Care Med 2014; 42:2083-2091 28. Roberts BW, Kilgannon JH, Chansky ME, et al: Association between postresuscitation partial pressure of arterial carbon dioxide and neu rological outcome in patients with post-cardiac arrest syndrome. Circulation 2013; 127:2107-2113
November 2014 • Volume 42 • Number 11
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Department of Critical Care Medicine University of Pittsburgh Medical Center Pittsburgh, PA Joseph Varon, M D , FACP, FCCP, FC C M , F R S M
Department of Acute and Continuing Care The University of Texas Health Science Center at Houston Houston, TX; Department of Medicine The University of Texas Medical Branch at Galveston Galveston, TX; and Department of Critical Care Services University General Hospital Houston, TX
ne of the most fundamental rules in medicine is “Primum Non Nocere”—to first, do no harm. However, unfortunately, sometimes our quest to “improve” physiologic variables in our patients can lead to harm; this is when “better” becomes the enemy of good. Recent examples of such unintended consequences include use of intensive insulin therapy to induce strict normoglycemia in critically ill patients, linked to increased risk of death (1, 2); the use of starches to improve hemodynamics and increase efficacy of resuscitation in patients with severe sepsis, linked to increased risk of renal failure and death (2, 3); excessive oxygenation in patients with out-of-hospital cardiac arrest (OHCA), linked to higher mor tality (4); aggressive treatment of intracranial arterial steno sis with elective stent placement in addition to drug therapy, linked to increased risk of stroke and higher mortality (5); use of long-acting (3-blockers to reduce cardiac risk in the peri operative setting, linked to increased risk of stroke and higher mortality (6); and quite possibly use of long-acting antihy pertensives in the acute phase of neurological injury, linked to increased mortality when “overshoot” (accidental hypoten sion) occurs (7). This list could easily be expanded. A recurrent theme in many of these interventions is an overzealous attempt to restore (perceived) physiological or ref erence values. Often it is the “overshoot” of efforts to restore “normal” values that is harmful, where the intervention itself may be neutral or even beneficial; but sometimes the concept
O
'See also p. 2401. Key Words: bradycardia; cardiac arrest; hypothermia; myocardial function; resuscitation The authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0000000000000600 2452
w w w .c c m jo u r n a l.o r g
of “normal” may change under pathophysiologic conditions, and trying to achieve “normal” values may itself be harmful. We should always keep in mind that for any given interven tion, risks may outweigh benefits and that our efforts to restore numbers to normal or supranormal could backfire. These observations come to mind when reading the article by Staer-Jensen et al (8) published in this issue of Critical Care Medicine. The authors, who work in a large tertiary referral cen ter for patients with OHCA, performed a retrospective cohort study in 111 of their patients to determine whether there was a link between bradycardia developing during therapeutic hypothermia (TH) and neurological outcome. The result may come as a surprise to some; the authors found that bradycardia during TH was associated with favorable neurologic outcome at hospital discharge. They conclude that bradycardia during TH should not be aggressively treated in most patients (8). The authors also established a dose-response relationship between bradycardia and favorable outcome, that is, the lower the heart rate, the greater the likelihood of favorable outcome. Although the study is limited by its retrospective design, finding such a dose-response relationship makes it more plausible that the observed link is genuine. These findings suggest that in many cases our desire for the heart rate to be “normal” under hypothermic conditions may be misguided and that attempts to “fix” the heart rate may be yet another example of better being the enemy of good. To better understand the results of this study, it is useful to take a brief look at the physiological links between temperature and heart rate. Hypothermia has multiple direct and indirect effects on heart rhythm and myocardial function. A mild drop in temperature to levels just below normal (±36.0°C) initially leads to an increase in plasma levels of norepinephrine and activation of the sympathetic nerve system. This induces con striction of peripheral vessels (particularly in the skin) and a shift of blood from peripheral (small) veins to deeper veins in the core compartment of the body, leading to an increase in venous return to the heart (9). This hypothermia-induced rise in venous return initially leads to mild sinus tachycardia and is one of the factors contributing to so-called cold diuresis (the others being a decrease in antidiuretic hormone [ADH] and renal ADH receptor levels, tubular dysfunction, and activa tion of atrial natriuretic peptide) (9). Cold diuresis can lead to hypovolemia, which can sustain and increase tachycardia (9). The initial increase in heart rate is reversed as core tem perature decreases further, below 35.5°C. Heart rate begins to drop progressively as core temperature decreases, and soon sinus bradycardia ensues; at 32°C, the normal heart rate will be 35-45 beats/min (although there is wide interpatient variabil ity). This is caused by a hypothermia-induced decrease in the rate of spontaneous depolarization of cardiac pacemaker cells, including those of the sinus node, combined with decreased November 2014 • Volume 42 • Number 11
Editorials
speed of myocardial impulse conduction and increased dura tion of action potentials (9). These changes are reflected in the patients’ electrocardiogram and may include prolonged PR intervals, increased QT interval, and widening QRS complex. Less frequently, so-called Osborne waves may develop (9,10). Some regard such changes as pathological and potentially harmful. Large studies assessing the efficacy of TH for vari ous types of neurologic injury have reported bradycardia as a side effect or arrhythmia (11); many hypothermia protocols and published reviews list “bradyarrhythmias” as an exclu sion criterion and recommend rewarming, chronotropic sup port, or pacemaker insertion if bradycardia develops (12-14). Others have argued in this journal and elsewhere that such changes are essentially physiologic adaptations, should not be regarded as pathological arrhythmia’s, and usually do not require treatment (9, 10, 15). The argument has pertained to mild-to-moderate hypothermia, that is, temperatures between 30°C and 35°C; it is well recognized that deep hypothermia, that is, temperature less than or equal to 28°C, does increase the risk of life-threatening arrhythmias (beginning with atrial fibrillation, followed by shock-resistant ventricular fibrillation, shock resistant in that deeply hypothermic myocardial tissue becomes more difficult to defibrillate, and less responsive to antiarrhythmic drugs) (9). However, there is compelling evidence that moderate hypo thermia has no such effect and that in fact the opposite is true: mild-to-moderate hypothermia decreases the risk of arrhyth mias and makes the myocardium less resistant to electric defi brillation. Boddicker et al (16) and Rhee et al (17) studied the effect of temperature on the likelihood of successful defibrilla tion in pigs. Both reported higher rates of return of spontane ous circulation, greater likelihood of successful defibrillation with fewer shocks required, and lower risk of postdefibrilla tion asystole under hypothermic conditions (15, 16). Even at 30°C, the results were better than at 37°C. Harada et al (18) reported similar findings in a rabbit model. Several case studies have reported successful use of TH to treat junctional ectopic tachycardia in children (19-21). Taken together, these find ings suggest that moderate hypothermia decreases the risk of arrhythmias and may facilitate their treatment if they do occur. Further, TH increases myocardial contractility in most patients (though mild diastolic dysfunction may occur), and blood pressure remains stable or increases unless the patient is hypovolemic (9, 10); but when hypothermia-induced bra dycardia is “treated” (i.e., heart rate is artificially increased to “normal” values), this leads to decreased myocardial contrac tility, worsening myocardial function, and increased myocar dial oxygen demand (22,23). These physiological observations and experimental data dovetail nicely with the results reported by Staer-Jensen et al (8). To be sure, their study has important limitations. Its ret rospective design makes it difficult to draw firm conclusions. The presence of tachycardia in patients during TH (including a “normal” heart rate, which should be regarded as tachycardia when a patient is hypothermic) may reflect more severe myo cardial injury or the presence of additional pathology such as Critical Care Medicine
preexisting infection or other disease. Absence of bradycardia may very well be a marker, rather than the cause of favorable outcome. Supporting this view is that on multivariate analysis, the authors found that bradycardia 8 hours postischemia was not significantly associated with better neurologic outcome when adjusting for all covariates (8). The question whether bradycardia actually improves out come can only be answered with a prospective randomized trial. Nevertheless, there are many theoretical considerations and experimental data suggesting that bradycardia might be favorable, and we should probably resist any urge to “fix” the low heart rate in most patients. Certainly, TH treatment should not be withheld because of the presence/risk of arrhythmias or bradycardia. Perhaps our mindset needs to change; rather than reflexively trying to “fix” temperature-appropriate low heart rates, maybe we should question why a given patient does not develop temperature-appropriate bradycardia. Perhaps there is shivering/discomfort? Maybe hypovolemia is present, due to cold diuresis and/or the postcardiac arrest syndrome that many cardiac arrest (CA) patients develop (24, 25)? Perhaps the apparent sinus rhythm is actually an underlying atrial flut ter? Maybe an infection is developing, due to aspiration before the airway was secured? Of note, while bradycardia appears to be an adaptive or even protective response, this very likely does not apply to hypo tension. Cerebral oxygenation depends mainly on perfusion pressure rather than cardiac output; especially when cerebral autoregulation is impaired (as is often the case after OHCA) (26), the brain is highly perfusion dependent. A recent study published in Critical Care Medicine found that average mean arterial pres sure (MAP) greater than or equal to 70 mm Hg in patients with OHCA was associated with better neurological outcome (27). All this suggests that we should look very carefully at our interventions and desired variables in patients with OHCA, particularly while undergoing TH. We should realize that bradycardia is the normal situation under hypothermic con ditions and that if something is not broken, we should prob ably not attempt to fix it. Patients with bradycardia who have a good MAP, urine production, and lactate clearance and accept able venous/mixed venous saturation likely do not require interventions. In general, we should strive to keep things as close to normal (for that individual patient) as possible, but the “normal” should be temperature adjusted. Bradycardia is normal, hypotension is not; hypo- and hypercapnia as well as hypoxia and hyperoxia should be avoided (4, 28), with blood gases being corrected for temperature (9,10). Future, prospective clinical trials should address what the optimal physiologic variables in post-CA patients should be. Apart from MAP, heart rate, and ventilation, these should include the optimal temperature and duration of therapeutic cooling. The current study provides guidance on how to manage our patients pending such trials, and again it reminds us that with appropriate management, the rate of survival with good neurologic outcome after witnessed ventricular tachycardia/ ventricular fibrillation arrest can and should be 50% or higher. w w w .c c m jo u r n a l.o r g
2453
Editorials
REFERENCES 1. Finfer S, Liu B, Chittock DR, et al; NICE-SUGAR Study Investigators: Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012;367:1108-1118 2. Brunkhorst FM, Engel C, Bloos F, et al; German Competence Network Sepsis (SepNet): Intensive insulin therapy and pentastarch resuscita tion in severe sepsis. N Engl J Med 2008; 358:125-139 3. PernerA,HaaseN,Guttormsen AB,etal;6STrialGroup;Scandinavian Critical Care Trials Group: Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012; 367:124-134 4. Kilgannon JH, Jones AE, Shapiro Nl, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators: Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA 2010; 303:2165-2171 5. Chimowitz Ml, Lynn MJ, Derdeyn CP, et al; SAMMPRIS Trial Investigators: Stenting versus aggressive medical therapy for intra cranial arterial stenosis. N Engl J Med 2011; 365:993-1003 6. Devereaux PJ, Yang H, Yusuf S, et al; POISE Study Group: Effects of extended-release metoprolol succinate in patients undergoing non cardiac surgery (POISE trial): A randomised controlled trial. Lancet 2008;371:1839-1847 7. Mayer SA, Kurtz P, Wyman A, et al; STAT Investigators: Clinical prac tices, complications, and mortality in neurological patients with acute severe hypertension: The Studying the Treatment of Acute hyperTension registry. Crlt Care Med 2011; 39:2330-2336 8. Strer-Jensen H, Sunde K, Olasveengen TM, et al: Bradycardia During Therapeutic Hypothermia Is Associated With Good Neurologic Outcome in Comatose Survivors of Out-of-Hospital Cardiac Arrest. Crit Care Med 2014; 42:2401 -2 4 0 8 9. Polderman KH: Therapeutic temperature management: State of the art in the critically ill: Mechanisms of action, physiologic effects and complications of hypothermia. Crlt Care Med 2009; 37:S186-S202 10. Polderman KH, Herold I: Therapeutic hypothermia and controlled normothermia in the intensive care unit: Practical considerations, side effects, and cooling methods. Crit Care Med 2009; 37:1101-1120 11. Clifton GL, Miller ER, Choi SC, et al: Lack of effect of induc tion of hypothermia after acute brain injury. N Engl J Med 2001; 344:556-563 12. Deckard ME: Therapeutic hypothermia after cardiac arrest: What, why, who, and how. Am Nurs Today 2011; 6:23-29 13. Oommen SS, Menon V: Hypothermia after cardiac arrest: Beneficial, but slow to be adopted. Cleve Clin J Med 2011; 78:441 -4 4 8 14. Lakshmanan R, Sadaka F, Palagiri A: Therapeutic hypothermia: Adverse events, recognition, prevention and treatment strategies. In'. Therapeutic Hypothermia in Brain Injury. Sadaka F (Ed). InTech 2013. Available at: http://www.intechopen.com/books/therapeutichypothermia-in-brain-injury/therapeutic-hypothermia-adverse-events-
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November 2014 • Volume 42 • Number 11
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