LETTERS
Paroxysmal sympathetic hyperactivity, traumatic brain injury, and A-blockers
TO THE
EDITOR
In conclusion, the available evidence gives BBs an important role in the management of patients with PHS syndrome;2Y5 however, the data provided by this study should be interpreted with great caution. *The authors declare no conflict of interest.
To the Editor: have read with great interest the article published by Schroeppel et al.1 In a retrospective analysis of 4 years, the authors conclude that propranolol is the A-blocker (BB) of choice to limit secondary damage caused by dysautonomia and thereby lower the mortality after traumatic brain injury (TBI).1 The paroxysmal sympathetic hyperactivity (PHS) syndrome is a secondary insult with potentially severe consequences.2Y5 Its incidence after severe TBI and diffuse axonal injury is 33%.3 The diagnosis is based on clinical picture, and certain diagnostic criteria were established to confirm it and to perform adequate differential diagnosis.4 The syndrome evolves into spells, which have certain specific characteristics to them, same as the time of occurrence in the evolution of TBI, its duration, the number of events per day, and maintenance of crises as time passes.2Y5 It is important to recognize PHS syndrome early because the delay in its recognition is clearly associated with refractoriness to therapeutic drugs.2,3,5 To abort crises, morphine is the drug of choice, while in the prevention of spells, BBs play an important role.2Y5 The topic is of great interest and importance; however, despite the limitations noted by the authors, there are other equally important points that deserve clarification. First, it is unclear for which were the indications of propranolol and in which time point in the evolution of TBI it was indicated. If the reason to indicate BB was dysautonomia (we prefer the term PHS syndrome2Y5), which criteria were used for the diagnosis and in what time point in the evolution it made its appearance? Second, what were the doses and route of administration? With which other BBs was it compared? What were the therapeutic goals and the rates of complications or failure in achieving the therapeutic target? Was therapeutic adjuvant, for example, morphine, used in the study population? Third, what was the real impact and incidence of PHS syndrome in the population? Finally, it is necessary that when we talk about TBI, lesional types (diffuse axonal injury, subdural or epidural hematoma, contusions) and categories of severity are specified. The mean Glasgow Coma Scale (GCS) score of the population was 11; in this situation, how many patients were classified as severe or moderate?
Daniel Agustı´n Godoy Neurocritical Care Unit Sanatorio Pasteur Intensive Care Unit Hospital San Juan Bautista Catamarca, Argentina
I
Gustavo Rene Pin˜ero Intensive Care Unit Hospital Municipal Leonidas Lucero Bahia Blanca Buenos Aires, Argentina
Luca Masotti Internal Medicine Santa Maria Nuova Hospital Florence, Italy
REFERENCES 1. Schroeppel TJ, Sharpe JP, Magnotti LJ, Weinberg JA, Clement LP, Croce MA, Fabian TC. Traumatic brain injury and A-blockers: not all drugs are created equal. J Trauma Acute Care Surg. 2014;76(2):504Y509; discussion 509. 2. Perkes I, Baguley IJ, Nott MT, Menon DK. A review of paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol. 2010;68(2):126Y135. 3. Rabinstein AA, Benarroch EE. Treatment of paroxysmal sympathetic hyperactivity. Curr Treat Options Neurol. 2008;10(2):151Y157. 4. Perkes IE, Menon DK, Nott MT, Baguley IJ. Paroxysmal sympathetic hyperactivity after acquired brain injury: a review of diagnostic criteria. Brain Inj. 2011;25(10):925Y932. 5. Choi HA, Jeon SB, Samuel S, Allison T, Lee K. Paroxysmal sympathetic hyperactivity after acute brain injury. Curr Neurol Neurosci Rep. 2013;13(8):370.
Re: Paroxysmal sympathetic hyperactivity, traumatic brain injury, and A-blockers: Not all drugs are created equal To the Editor: e appreciate the interest in our article1 by Godoy et al. While many terms have been used for the sympathetic hyperactivity that can occur after traumatic brain
W
injury (TBI), the letter writers prefer the term paroxysmal sympathetic hyperactivity (PSH) syndrome.2 The logic behind this term is sound, but it would seem that paroxysms are necessary for this term to be reflective of the condition. We did not observe paroxysms in our patient population, which are the basis for this term. While parasympathetic abnormalities were not routinely present in this population, we think that dysautonomia is the more appropriate term to be consistent with the literature. While some of the answers to the letter writers’ questions are available, many are not due to the retrospective nature of the study. The indications for propranolol (PRO) were sympathetic hyperactivity including tachycardia, hypertension, and fever. The time course for initiation of the drug was variable, as a formal protocol was not in place during the study. Ideally, PRO should be started as soon as possible provided that resuscitation is complete for any associated injuries. Definitive recommendations on treatment initiation and duration need to be investigated in a prospective trial. A formal protocol was not used for dose or route of PRO during the study period. Our practice pattern was to start at 20 mg orally twice a day. This was increased to three times daily, and dose was increased if therapeutic effect was not realized. The most common variable used for titration was heart rate, with fewer than 100 beats per minute as the target. There were no complications with the drug during the study period. We do not have data on the number of patients who failed to reach therapeutic target. As stated in the article, the other A-blockers (BBs) used included atenolol, carvedilol, esmolol, labetalol, metoprolol, PRO, and sotalol. The most common agents were labetalol and metoprolol. While we did not specifically use morphine as an adjunct to treat PSH syndrome, pain control is necessary and frequently used in trauma patients with multiple injuries. Fentanyl, morphine, and hydromorphone were given frequently to all patients in the study. Lastly, since we did not appreciate PSH syndrome in our patients, we do not have the data for incidence and impact of this condition in this study. Time of initiation of the drug, ideal dose, and treatment duration need to be investigated and better defined in a prospective trial. To exclude minor and nonsurvivable TBI, head Abbreviated Injury Scale (AIS) scores of less than 3 and greater than 5 were excluded. The target population would then have moderate and severe head injury. While the mean admission Glasgow Coma Scale (GCS) score for the study was 11, the mean for BB and PRO was 9 and 6, respectively. We
J Trauma Acute Care Surg Volume 77, Number 2
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
387
J Trauma Acute Care Surg Volume 77, Number 2
Letters to the Editor
did not further categorize beyond AIS score as that was not the purpose of the study. All types of TBIs were included in the analysis including cerebral contusion, epidural hematoma, subdural hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, and diffuse axonal injury. In conclusion, Godoy et al. have some valid concerns that are shared by the authors. The purpose of the study was not to answer all the questions posed by them, but to investigate any potential benefit of PRO compared with other BBs. We think that the available evidence supports the safety and potential benefit of BB and PRO in this population,
388
with few, if any, complications. We have designed a prospective study to answer many of the questions and are currently applying for funding. We think that all retrospective studies need to be interpreted with caution until verified by prospective investigations.
*The authors declare no conflicts of interest.
Thomas J. Schroeppel, MD Martin A. Croce, MD Timothy C. Fabian, MD
Department of Surgery University of Tennessee Health Science Center Memphis, TN
REFERENCES 1. Schroeppel TJ, Sharpe JP, Magnotti LJ, Weinberg JA, Clement LP, Croce MA, Fabian TC. Traumatic brain injury and A-blockers: not all drugs are created equal. J Trauma Acute Care Surg. 2014;76:504Y509. 2. Perkes I, Baguley IJ, Nott MT, Menon BK. A review or paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol. 2010;68:126Y135.
* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Paroxysmal sympathetic hyperactivity, traumatic brain injury, and A-blockers
TO THE
EDITOR
In conclusion, the available evidence gives BBs an important role in the management of patients with PHS syndrome;2Y5 however, the data provided by this study should be interpreted with great caution. *The authors declare no conflict of interest.
To the Editor: have read with great interest the article published by Schroeppel et al.1 In a retrospective analysis of 4 years, the authors conclude that propranolol is the A-blocker (BB) of choice to limit secondary damage caused by dysautonomia and thereby lower the mortality after traumatic brain injury (TBI).1 The paroxysmal sympathetic hyperactivity (PHS) syndrome is a secondary insult with potentially severe consequences.2Y5 Its incidence after severe TBI and diffuse axonal injury is 33%.3 The diagnosis is based on clinical picture, and certain diagnostic criteria were established to confirm it and to perform adequate differential diagnosis.4 The syndrome evolves into spells, which have certain specific characteristics to them, same as the time of occurrence in the evolution of TBI, its duration, the number of events per day, and maintenance of crises as time passes.2Y5 It is important to recognize PHS syndrome early because the delay in its recognition is clearly associated with refractoriness to therapeutic drugs.2,3,5 To abort crises, morphine is the drug of choice, while in the prevention of spells, BBs play an important role.2Y5 The topic is of great interest and importance; however, despite the limitations noted by the authors, there are other equally important points that deserve clarification. First, it is unclear for which were the indications of propranolol and in which time point in the evolution of TBI it was indicated. If the reason to indicate BB was dysautonomia (we prefer the term PHS syndrome2Y5), which criteria were used for the diagnosis and in what time point in the evolution it made its appearance? Second, what were the doses and route of administration? With which other BBs was it compared? What were the therapeutic goals and the rates of complications or failure in achieving the therapeutic target? Was therapeutic adjuvant, for example, morphine, used in the study population? Third, what was the real impact and incidence of PHS syndrome in the population? Finally, it is necessary that when we talk about TBI, lesional types (diffuse axonal injury, subdural or epidural hematoma, contusions) and categories of severity are specified. The mean Glasgow Coma Scale (GCS) score of the population was 11; in this situation, how many patients were classified as severe or moderate?
Daniel Agustı´n Godoy Neurocritical Care Unit Sanatorio Pasteur Intensive Care Unit Hospital San Juan Bautista Catamarca, Argentina
I
Gustavo Rene Pin˜ero Intensive Care Unit Hospital Municipal Leonidas Lucero Bahia Blanca Buenos Aires, Argentina
Luca Masotti Internal Medicine Santa Maria Nuova Hospital Florence, Italy
REFERENCES 1. Schroeppel TJ, Sharpe JP, Magnotti LJ, Weinberg JA, Clement LP, Croce MA, Fabian TC. Traumatic brain injury and A-blockers: not all drugs are created equal. J Trauma Acute Care Surg. 2014;76(2):504Y509; discussion 509. 2. Perkes I, Baguley IJ, Nott MT, Menon DK. A review of paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol. 2010;68(2):126Y135. 3. Rabinstein AA, Benarroch EE. Treatment of paroxysmal sympathetic hyperactivity. Curr Treat Options Neurol. 2008;10(2):151Y157. 4. Perkes IE, Menon DK, Nott MT, Baguley IJ. Paroxysmal sympathetic hyperactivity after acquired brain injury: a review of diagnostic criteria. Brain Inj. 2011;25(10):925Y932. 5. Choi HA, Jeon SB, Samuel S, Allison T, Lee K. Paroxysmal sympathetic hyperactivity after acute brain injury. Curr Neurol Neurosci Rep. 2013;13(8):370.
Re: Paroxysmal sympathetic hyperactivity, traumatic brain injury, and A-blockers: Not all drugs are created equal To the Editor: e appreciate the interest in our article1 by Godoy et al. While many terms have been used for the sympathetic hyperactivity that can occur after traumatic brain
W
injury (TBI), the letter writers prefer the term paroxysmal sympathetic hyperactivity (PSH) syndrome.2 The logic behind this term is sound, but it would seem that paroxysms are necessary for this term to be reflective of the condition. We did not observe paroxysms in our patient population, which are the basis for this term. While parasympathetic abnormalities were not routinely present in this population, we think that dysautonomia is the more appropriate term to be consistent with the literature. While some of the answers to the letter writers’ questions are available, many are not due to the retrospective nature of the study. The indications for propranolol (PRO) were sympathetic hyperactivity including tachycardia, hypertension, and fever. The time course for initiation of the drug was variable, as a formal protocol was not in place during the study. Ideally, PRO should be started as soon as possible provided that resuscitation is complete for any associated injuries. Definitive recommendations on treatment initiation and duration need to be investigated in a prospective trial. A formal protocol was not used for dose or route of PRO during the study period. Our practice pattern was to start at 20 mg orally twice a day. This was increased to three times daily, and dose was increased if therapeutic effect was not realized. The most common variable used for titration was heart rate, with fewer than 100 beats per minute as the target. There were no complications with the drug during the study period. We do not have data on the number of patients who failed to reach therapeutic target. As stated in the article, the other A-blockers (BBs) used included atenolol, carvedilol, esmolol, labetalol, metoprolol, PRO, and sotalol. The most common agents were labetalol and metoprolol. While we did not specifically use morphine as an adjunct to treat PSH syndrome, pain control is necessary and frequently used in trauma patients with multiple injuries. Fentanyl, morphine, and hydromorphone were given frequently to all patients in the study. Lastly, since we did not appreciate PSH syndrome in our patients, we do not have the data for incidence and impact of this condition in this study. Time of initiation of the drug, ideal dose, and treatment duration need to be investigated and better defined in a prospective trial. To exclude minor and nonsurvivable TBI, head Abbreviated Injury Scale (AIS) scores of less than 3 and greater than 5 were excluded. The target population would then have moderate and severe head injury. While the mean admission Glasgow Coma Scale (GCS) score for the study was 11, the mean for BB and PRO was 9 and 6, respectively. We
J Trauma Acute Care Surg Volume 77, Number 2
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
387
J Trauma Acute Care Surg Volume 77, Number 2
Letters to the Editor
did not further categorize beyond AIS score as that was not the purpose of the study. All types of TBIs were included in the analysis including cerebral contusion, epidural hematoma, subdural hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, and diffuse axonal injury. In conclusion, Godoy et al. have some valid concerns that are shared by the authors. The purpose of the study was not to answer all the questions posed by them, but to investigate any potential benefit of PRO compared with other BBs. We think that the available evidence supports the safety and potential benefit of BB and PRO in this population,
388
with few, if any, complications. We have designed a prospective study to answer many of the questions and are currently applying for funding. We think that all retrospective studies need to be interpreted with caution until verified by prospective investigations.
*The authors declare no conflicts of interest.
Thomas J. Schroeppel, MD Martin A. Croce, MD Timothy C. Fabian, MD
Department of Surgery University of Tennessee Health Science Center Memphis, TN
REFERENCES 1. Schroeppel TJ, Sharpe JP, Magnotti LJ, Weinberg JA, Clement LP, Croce MA, Fabian TC. Traumatic brain injury and A-blockers: not all drugs are created equal. J Trauma Acute Care Surg. 2014;76:504Y509. 2. Perkes I, Baguley IJ, Nott MT, Menon BK. A review or paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol. 2010;68:126Y135.
* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
